Molecular cytogenetic mapping of 24 CEPH YACs and 24 gene-specific large insert probes to chromosome 17.
Defining boundaries of chromosomal rearrangements at the molecular level would benefit from landmarks that link the cytogenetic map to physical, genetic, and transcript maps, as well as from large-insert FISH probes for such loci to detect numerical and structural rearrangements in metaphase or interphase cells. Here, we determined the locations of 24 genetically mapped CEPH-Mega YACs along the FLpter scale (fractional length from p-telomere) by quantitative fluorescence in situ hybridization analysis. This generated a set of cytogenetically mapped probes for chromosome 17 with an average spacing of about 5 cM. We then developed large-insert YAC, BAC, PAC, or P1 clones to the following 24 known genes, and determined refined map locations along the same FLpter scale: pter-TP53-TOP3-cen-TNFAIP1-ERBB2-TOP2A- BRCA1-TCF11-NME1-HLF-ZNF147/CL N80-BCL5/MPO/SFRS1-TBX2-PECAM1-DDX5/ PRKCA-ICAM2-GH1/PRKAR1A-GRB2-CDK3 /FKHL13-qter. Taken together, these 48 cytogenetically mapped large-insert probes provide tools for the molecular analysis of chromosome 17 rearrangements, such as mapping amplification, deletion, and translocation breakpoints in this chromosome, in cancer and other diseases.


Impact of Spartina alterniflora Invasion in Coastal Wetlands of China: Boon or Bane?
Invasive plants, like Spartina alterniflora (SA), have a competitive advantage over native flora due to their rapid utilization of vital soil nutrients. This results in the depletion of resources for native plant species, significantly impacting ecosystem diversity and stability. This comprehensive review addresses several key aspects related to SA's spread and spatial distribution in China's wetlands. The rapid expansion of Spartina alterniflora is attributed to its high reproductive ability, adaptability to environmental factors like elevated salinity, and ability to disperse its seeds via tides. Spartina alterniflora mainly were found in Zhejiang, Jiangsu, Fujian, and Shanghai provinces, accounting for more than 90% of China's total Spartina alterniflora area. Spartina alterniflora rapid growth results in displacement of native species and loss of vital microbial, plant, and animal diversity. Some studies reported that Spartina alterniflora increases carbon storage, while others argue that it weakens this function. The impact of Spartina alterniflora on organic and inorganic carbon requires further research for better understanding dynamics of carbon in coastal wetlands. The controlled growth of Spartina alterniflora can be beneficial in many aspects of the coastal wetlands' ecosystem. In China, various methods have been employed to control the invasion of SA. Physical control, such as removing the plants and converting them into fertilizer or bioenergy, has been commonly used but has limitations like air pollution and the potential for re-invasion. Chemical herbicides like Imazapyr and Haloxyfop-R-methyl have effectively controlled and prevented re-invasion in specific areas, but their potential adverse impacts are still uncertain. Wetland Park construction, aquaculture development, and substituting native or exotic species with mangroves or reed communities have also been successful. It becomes evident that a long-standing and Contextual approach is necessary to effectively manage the advantages and curtail the drawbacks associated with S. alterniflora across China.


Association of Selective Serotonin Reuptake Inhibitor Use With Abnormal Physical Movement Patterns as Detected Using a Piezoelectric Accelerometer and Deep Learning in a Nationally Representative Sample of Noninstitutionalized Persons in the US.
Selective serotonin reuptake inhibitors (SSRIs) are a common first-line treatment for some psychiatric disorders, including depression and anxiety; although they are generally well tolerated, SSRIs have known adverse effects, including movement problems, sleep disruption, and gastrointestinal problems (eg, nausea and upset stomach). No large-scale studies using naturalistic, longitudinal, objective data have validated physical activity findings, and actigraphy data are well suited to address this task. To evaluate whether differences in physical movement exist among individuals treated with SSRIs compared with control participants and to identify the unique features of the movement of patients treated with SSRIs. This cross-sectional study examines longitudinally collected wearable movement data within a cross-sectional sample of 7162 participants from the 2005-2006 National Health and Nutrition Examination Survey (NHANES), a nationally representative population-based sample of noninstitutionalized persons in the US having both medication information and passive movement data. Statistical analysis was performed from April 1, 2021, to February 1, 2022. The use of SSRIs (sertraline hydrochloride, escitalopram oxalate, fluoxetine hydrochloride, paroxetine hydrochloride, and citalopram hydrobromide), as reported by participants interviewed by NNHANES personnel, was the primary exposure, measured as a binary variable (taking an SSRI vs not taking an SSRI). The primary outcome was the intensity of body movement as recorded by a piezoelectric accelerometer worn on the right hip for more than 1 week. Of the 7162 participants included in the study, the mean (SD) age was 33.7 (22.6) years, 266 (3.7%) were taking an SSRI, 3706 (51.7%) were female, 1934 (27.0%) were Black, 1823 (25.5%) were Mexican American, 210 (2.9%) were other Hispanic, 336 (4.7%) were other or multiracial, and 2859 (39.9%) were White (per the NHANES data collection protocol). A cross-validated, deep learning classifier was constructed that achieved fair performance predicting SSRI use (area under the curve, 0.67 [95% CI, 0.64-0.71] for the validation set and 0.66 [95% CI, 0.64-0.68] for the test set). To account for possible confounding by indication, we constructed a parallel model incorporating depression severity, finding only marginal performance improvement. When averaged across individuals and across 7 days, the results show less overall movement in the SSRI group (mean, 120.1 vertical acceleration counts/min [95% CI, 115.7-124.6 vertical acceleration counts/min]) compared with the non-SSRI control group (mean, 168.8 vertical acceleration counts/min [95% CI, 162.8-174.9 vertical acceleration counts/min]). This cross-sectional study found a moderate association between passive movement and SSRI use, as well as SSRI detection capacity of passive movement using time series deep learning models. The results support the use of passive sensors for exploration and characterization of psychotropic medication adverse effects.


High-valency Anti-CD99 Antibodies Toward the Treatment of T Cell Acute Lymphoblastic Leukemia.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive form of leukemia that currently requires intensive chemotherapy. While childhood T-ALL is associated with high cure rates, adult T-ALL is not, and both are associated with significant short- and long-term morbidities. Thus, less toxic and effective strategies to treat T-ALL are needed. CD99 is overexpressed on T-ALL blasts at diagnosis and at relapse. Although targeting CD99 with cytotoxic antibodies has been proposed, the molecular features required for their activity are undefined. We identified human antibodies that selectively bound to the extracellular domain of human CD99, and the most potent clone, 10A1, shared an epitope with a previously described cytotoxic IgM antibody. We engineered clone 10A1 in bivalent, trivalent, tetravalent, and dodecavalent formats. Increasing the antibody valency beyond two had no effects on binding to T-ALL cells. In contrast, a valency of ≥3 was required for cytotoxicity, suggesting a mechanism of action in which an antibody clusters ≥3 CD99 molecules to induce cytotoxicity. We developed a human IgG-based tetravalent version of 10A1 that exhibited cytotoxic activity to T-ALL cells but not to healthy peripheral blood cells. The crystal structure of the 10A1 Fab in complex with a CD99 fragment revealed that the antibody primarily recognizes a proline-rich motif (PRM) of CD99 in a manner reminiscent of SH3-PRM interactions. This work further validates CD99 as a promising therapeutic target in T-ALL and defines a pathway toward the development of a selective therapy against T-ALL.


Exertion-induced heatstroke.
A case of exertion-induced heatstroke which illustrates the multiple complications of hyperthermia, including jaundice, coagulopathy and cardiac abnormalities, is reported. The need to increase public awareness of the danger of hyperthermia, and of preventive and first-aid measures, is emphasized.


Testing Communication Concepts on COVID-19 Contact Tracing Among Black and Latinx/Hispanic People in the United States.
Black and Latinx/Hispanic people were more than twice as likely to die from COVID-19 than White people, but because of legacies of discrimination and maltreatment in health care, were less likely to participate in some public health responses to COVID-19, including contact tracing. This study aimed to test three communication campaign concepts to engage Black and Latinx/Hispanic people in contact tracing efforts. Twelve focus group discussions with 5 to 10 participants each were conducted online among participants from Black and Latinx/Hispanic urban populations in Philadelphia and New York state. Participants provided sociodemographic information and were presented with potential campaign concepts and prompted to rate the concepts and engage in open-ended discussion. For rating and sociodemographic data, chi-square tests were performed. For open-ended discussion data, a thematic analysis approach was used. Across groups, the campaign concept that was rated most likely to encourage cooperation with contact tracing efforts was "Be the One," with 45% of total first-place votes. Participants expressed that the campaign caught their attention (79%), motivated them to engage with contact tracers (71%) and to talk to others about contact tracing (77%). Discussions also elucidated: the importance of community engagement; the need for clearer explanations of contact tracing; the preference for already trusted, community-based contact tracers; the need to reassure people about confidentiality; and for contact tracing to be culturally competent and empathetic. This study highlights how strategic, culturally sensitive communication can buttress current and future contact tracing efforts, especially among Black and Latinx/Hispanic people.


"Sleep benefit" in Parkinson's disease: a systematic review.
Sleep disorders are common among patients with Parkinson's disease (PD). However, there are also reports of PD patients experiencing a beneficial effect of sleep. Upon awaking in the morning some patients experience good mobility, as if they are in an "on" state induced by medication, contrary to what would be expected after a night without medication. This intriguing phenomenon is known as sleep benefit. Here, we review the available research on sleep benefit in PD, describing its prevalence, clinical effects and determinants. We also discuss the possible mechanisms underlying sleep benefit, and the potential clinical applicability. Finally, we propose a new definition of sleep benefit to allow for improved standardization and homogeneity in future research. Important research targets include the development of objective measures of sleep benefit, as a basis for obtaining a better understanding of sleep benefit, its underlying mechanisms and its potential therapeutic application.


Comparison of behavioral and radioprotective effects of WR-2721 and WR-3689.
The behavioral effects of the radioprotectant agents ethiofos, S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) and S-2-(3-methylaminopropyl)aminoethylphosphorothioic acid (WR-3689) were evaluated in rats trained to respond under a multiple fixed-interval 120-s, fixed-ratio 50-response (mult FI FR) schedule of milk reinforcement. Each compound produced dose-dependent reductions in responding under both schedules over the same dose range (100-180 mg/kg, IP); ED50s indicated that WR-3689 was slightly more potent than WR-2721. On several performance measures, WR-3689 produced greater decrements during a second dose-effect determination, whereas WR-2721 had more pronounced effects during the initial one. In a second series of studies, low (56 mg/kg) and high (180 mg/kg) doses of both drugs were tested for radioprotective effects in rats responding under an FR-50 schedule of milk reinforcement and exposed to a nonlethal (5 gray, Gy) or lethal (10 Gy) dose of ionizing radiation (60Co gamma rays). Neither dose of radiation altered FR response rates on the day of exposure (day 1). Five Gy of gamma radiation produced a 25-40% reduction in response rates on days 2-5 (24-72 h) after exposure. Neither dose of WR-2721 or WR-3689 provided significant protection against these performance decrements. All groups exposed to 10 Gy experienced a progressive decline in FR responding on days 2-5 after exposure. Performance of groups that received pretreatment with the 180-mg/kg dose of either drug or the 56-mg/kg dose of WR-3689 was maintained at significantly higher levels than saline-treated controls on days 4-5 after exposure to 10 Gy; however, even at these higher levels of performance response rates remained below 50% of preirradiation control levels. Subsequently, 56 and 180 mg/kg WR-3689 and 180 mg/kg WR-2721 were found to provide protection against the lethal consequences of the 10-Gy exposure. Thus, neither WR-2721 nor WR-3689 afforded any significant short-term protection against radiation-induced performance decrements when these drugs were administered at either behaviorally ineffective or behaviorally disruptive doses. Rather, the beneficial effects of these drugs paralleled their ability to antagonize radiation-induced lethality.


Metabolic disposition and excretion of quinocetone in rats, pigs, broilers, and carp.
Excretion, disposition, and metabolism of [(3)H]-quinocetone in rats, pigs, broilers, and carp following oral administration were investigated. After a single p.o. dose, total radioactivity was rapidly excreted, with ⩾94% in all species within 14 days. Fecal excretion of radioactivity was 68% and 65% of the administered dose in rats and pigs, respectively, with the remainder excreted in the urine. Six hours after the last of seven daily oral administrations of (3)H-labeled QCT, radioactivity was found to be distributed throughout all tissues, with the majority of radioactivity cleared within 7 days, and elimination was the slowest from the liver and kidney. QCT was extensively metabolized in all of the species, and the primary changes included N-O group reduction, carbonyl group reduction, double bond reduction, and hydroxylation. The major tissue metabolites of QCT were Q2, Q4, Q5, Q8, and Q9 in rats; Q1, Q2, Q3, Q4, and Q5 in pigs; Q1, Q2, Q3, Q4, and Q7 in broilers; and Q1, Q2 in carp. This confirmed the potential link between QCT metabolism through N-O group reduction and its organ toxicity. The results of the present study provide important data that could help understand the relationship between the toxicities and metabolic disposition of QCT.


New conjugated urinary metabolites in intermediate type maple syrup urine disease.
N-Lactylvaline, N-lactylleucine, N-lactylisoleucine and the N-2-hydroxyisovaleryl conjugates of glycine, valine, leucine and isoleucine have been identified in urine from a patient with the intermediate type of maple syrup urine disease.


Nephron electrolyte transport and sodium-potassium adenosine triphosphatase activity: influence of nicotine in rat and rabbit.
1. The influence upon mammalian renal epithelial transport of L-nicotine was studied in different types of experiments. 2. The kidney in situ (rat), when infused with nicotine (1 mg hr-1 kg-1 I.V.), lowered its absolute and fractional K+-absorption significantly and reversibly, but Na+-absorption did not change. Effects on glomerular function and an irreversible effect upon epithelial Na+ and K+ absorption were prevailing at higher infused amounts (10 or 50 mg hr-1 kg-1). 3. Single dissected nephron segments (collecting tubule, rabbit) were perfused in vitro, and the Na+ and K+-transtubular net flux was measured while L-nicotine (50 ng/ml.) had been added to the contraluminal side of the epithelium. Both, Na+-absorption and K+-secretion were decreased reversibly. 4. The activity of the Na+-K+-activated ATPase was significantly decreased in the cortical collecting tubule and in the proximal convoluted tubule of the rabbit after incubation of single in vitro dissected nephron segments with L-nicotine (50 or 100 ng/ml.). In contrast, nicotine added to a homogenate of renal cortical tissue had no effect on the Na+-transport enzyme or on key enzymes of glycolysis and gluconeogenesis. 5. These observations on the kidney in situ and on defined, perfused and non-perfused nephrons in vitro suggest that L-nicotine has dose-dependent, direct epithelial and mediated systemic effects on mammalian renal ion transport.


EGFRvIII epigenetically regulates ARHI to promote glioma cell proliferation and migration.
Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation widely expressed in glioma. However, its role and molecular mechanism in glioma have not been completely elucidated. Immunohistochemistry analyses of EGFRvIII, enhancer of zeste homolog 2 (EZH2) and aplysia ras homolog I (ARHI) were performed in tumor tissues from patients with glioma. Regulatory mechanisms among EGFRvIII, EZH2 and ARHI were examined by western blot and chromatin immunoprecipitation (ChIP). Cell proliferation and migration of glioma cells were examined. EGFRvIII and EZH2 expression were upregulated, while ARHI was downregulated in glioma tissues. EZH2 knockdown increased ARHI expression in glioma cell lines. ChIP assay suggested that EZH2 was enriched in the ARHI promoter. Furthermore, ectopic expression of EGFRvIII upregulated EZH2, suppressed ARHI expression, and promoted glioma cell proliferation. Additionally, treatment with 3-deazaneplanocin A (DZNep, an inhibitor of EZH2) inhibited expression of EZH2, increased protein level of ARHI, and partially abrogated the promoting effects of ARHI knockdown on glioma cell proliferation and migration. In summary, EGFRvIII-mediated epigenetic suppression of ARHI promoted glioma cell proliferation and migration via upregulating EZH2.


Improved detection of Shigella using Escherichia coli medium enrichment: Polymerase chain reaction from stool samples.
Laboratory diagnosis of shigellosis using conventional culture technique is limited by lower sensitivity and higher turnaround time. Here, we have evaluated the role of polymerase chain reaction from stool samples after enrichment in Escherichia coli medium for detection of Shigellae. The technique not only increased the sensitivity but also decreased the turnaround time.


Conformational selection, dynamic restriction and the hydrophobic effect coupled to stabilization of the BIR3 domain of the human X-linked inhibitor of apoptosis protein by the tetrapeptide AVPI.
The XIAP-BIR3 domain blocks a substantial portion of the apoptosis pathway and is an attractive target for novel anticancer agents. The tetrapeptide AVPI, from the protein Smac/DIABLO, binds to the XIAP-BIR3 domain, allowing the cancer cells to die. Here we characterize the binding parameters of AVPI to XIAP-BIR3 and analyze its effects on the thermodynamic stability of this domain. XIAP-BIR3 was exceptionally stable against physical and chemical treatments and became even more stable by interaction with AVPI. Nuclear magnetic resonance experiments demonstrated that conformational selection is taking place upon AVPI interaction with XIAP-BIR3. Molecular dynamics simulations corroborate that the flexibility of XIAP-BIR3 is significantly reduced. The positive binding entropy associated with a loss of conformational entropy involved in the binding indicates that hydrophobic interactions play an important role in the interaction and domain stabilization. The mechanism of XIAP-BIR3 stabilization and its implications for drug affinity optimization are discussed.


A cohort study of caries incidence and baseline socioeconomic, clinical and demographic variables: a Kaplan-Meier survival analysis.
To determine the incidence of dental caries and evaluate the influence of socioeconomic, clinical and demographic variables on the time for disease to appear in the permanent teeth after 3 years of follow-up. The random sample of this cohort study consisted of 427 5-year-old preschool children attending 22 public preschools in Piracicaba, SP, Brazil. Dental caries was measured using the dmf/DMF indices. The Kaplan- Meier survival analysis method was used to study the isolated effect of socioeconomic, clinical and demographic variables on caries incidence after 3 years. A Cox proportional hazards regression model was built to test the influence of the variables collected at baseline on time to develop DMFT increment. Survival analysis showed that children without past caries experience in primary teeth at baseline remained caries free in permanent teeth for a longer period than children with past caries experience at baseline. The variables monthly family income, parents' educational level, number of people living in the household, home ownership and car ownership were not significant. Children who presented past caries experience in primary teeth at baseline are at greater risk of developing DMFT increment than children who have no past caries experience at baseline.


Feasibility of Implementing a Total Worker Health® Intervention During the COVID-19 Pandemic in Small and Medium Businesses : Results From the Carolina PROSPER Study.
In response to the COVID-19 pandemic's disruptive effect on employers and workers, an interdisciplinary team launched the Carolina Promoting Safe Practices for Employees' Return study to assess the feasibility of providing tailored technical assistance to small and medium North Carolina businesses using a Total Worker Health (TWH) ® approach. Feasibility of the approach was assessed via surveys and interviews of business representatives from four participating businesses ranging in size from 3 to 110 employees. The TWH approach is feasible, that is, in demand, practical, and acceptable to protect and promote worker safety, health, and well-being. Potential challenges include implementation cost, difficulty engaging all employees, and difficulty accessing tailored health and safety materials in a timely manner. Additional refinement and testing of the TWH approach postpandemic with more worksites is warranted.


Distinctive immunoglobulin VH gene usage in Japanese patients with chronic lymphocytic leukemia.
The incidence of chronic lymphocytic leukemia (CLL) is low in Asian countries including Japan, while CLL is the most common type of leukemia in the west. To elucidate which factors contribute to the low frequency of CLL in Japan, we investigated immunoglobulin (Ig) heavy chain gene usage and somatic hypermutation status in 44 Japanese patients with CLL. Only one of these patients used V(H)1-69. The finding is in striking contrast to data from western countries, where the frequency of CLL expressing V(H)1-69 ranges from 12 to 21%.


Heterotrophic denitrification at extremely high salt and pH by haloalkaliphilic Gammaproteobacteria from hypersaline soda lakes.
In this paper we describe denitrification at extremely high salt and pH in sediments from hypersaline alkaline soda lakes and soda soils. Experiments with sediment slurries demonstrated the presence of acetate-utilizing denitrifying populations active at in situ conditions. Anaerobic enrichment cultures at pH 10 and 4 M total Na(+) with acetate as electron donor and nitrate, nitrite and N(2)O as electron acceptors resulted in the dominance of Gammaproteobacteria belonging to the genus Halomonas. Both mixed and pure culture studies identified nitrite and N(2)O reduction as rate-limiting steps in the denitrification process at extremely haloalkaline conditions.


DNase1 footprints suggest the involvement of at least three types of transcription factors in the regulation of alpha-Amy2/A by gibberellin.
To elucidate the mechanisms by which alpha-amylase genes are expressed in wild oat aleurone, two genes, alpha-Amy2/A and alpha-Amy2/D, were isolated. Both were shown to be positively regulated by gibberellin (GA) during germination and both contain the conserved cis-acting elements Box 2, GA-response element (TAACAGA) and TATCSATSS (where S is C or G). In addition, they possess a conserved initiator element (CATCA) that is present in both alpha-Amy2 and alpha-Amy1 genes, and also in a number of other plant TATA-containing and TATA-less promoters. DNase 1 footprint analysis showed the alpha-Amy2/A promoter to be a complex array of binding sites for a number of different classes of DNA-binding proteins. Our data suggest that the area around the initiator element (Inr) is bound by a large complex of general transcription factors, that the TATA box is bound by the TFIID complex, that Box 2 is bound by one or more WRKY proteins and that the GA-response element is bound by one or more MYBs. Two other elements containing the core sequence CCATGG/C are bound by nuclear protein and this sequence is the core of the Sph element. The regulation of alpha-Amy2 genes by GA therefore involves an interplay of at least three different types of transcription factor.


Progressive vascular lesions in Williams-Beuren syndrome.
We report two patients with Williams-Beuren syndrome. The first patient showed no evidence of coarctation of the aorta at the first examination. Seven years later, she developed coarctation of the aorta. In the second patient, we found the progression of renal artery stenosis by serial angiography. We report that vascular lesions may be progressive in Williams-Beuren syndrome.


Fusarium mycotoxins in forage maize - Detection and evaluation.
The deoxynivalenol concentrations found in forage maize ranged between 0.24 and 14.29 mg/kg DM (detected by ELISA). When highly contaminated samples were analysed for deoxynivalenol by HPLC or LC-MS the resulting concentrations were in the mean about 50% lower. Furthermore, using LC-MS other type-A and type-B trichothecenes, zearalenone and α-zearalenol were found in these samples. The differences between ELISA and HPLC/LC-MS data for deoxynivalenol are assumed to result from cross-reactions of other trichothecenes with the antibodies used in ELISA and toxin losses from sample purification procedures needed for HPLC and LC-MS analysis.


Alkaptonuria with extensive ochronotic degeneration of the Achilles tendon and its surgical treatment: a case report and literature review.
Alkaptonuria is a rare genetic metabolic disorder due to deficiency of homogentisate 1,2-dioxygenase (HGD), an enzyme catalyzing the conversion of homogentisate to 4-maleylacetoacetate in the pathway for the catabolism of phenylalanine and tyrosine. HGD deficiency results in accumulation of homogentisic acid and its pigmented polymer. Ochronosis is a bluish-black discoloration due to the deposition of the polymer in collagenous tissues. Extensive ochronotic involvement of the Achilles tendon in alkaptonuria and its surgical treatment is rarely reported. A 43-year-old man presented to our clinic in March 2019 with sudden onset of left Achilles tendon pain with no history of prior trauma. Surgical exploration revealed a complete disruption of the tendon at its attachment to the calcaneus. Black pigmentation was extensive and reached the calcaneal tuberosity, extending about 7 cm from the insertion. Achilles reconstruction was performed using flexor hallucis longus tendon transfer. The patient experienced uncomplicated healing with satisfactory functional results. Orthopedic surgeons should be aware of the progressive nature of alkaptonuria. Extensive degenerative changes of the ruptured tendon should be suspected so that physicians can plan tendon repair and facilitate prompt surgical intervention.


EFFECTS OF DEXTRAN-GRAFT-POLYACRYLAMIDE/ZnO NANOPARTICLES ON PROSTATE CANCER CELL LINES IN VITRO.
The combination of zinc oxide (ZnO) nanoparticles (NPs) with carriers enhances the anticancer effect of nanocomposites. To explore the mechanisms of cytotoxic action of dextran-graft-polyacrylamide (D-g-PAA/ZnO) NPs against prostate cancers cell lines in vitro. Dextran-polyacrylamide was used as a matrix for the synthesis of ZnO NPs. Prostate cancer cells LNCaP, DU-145 and PC-3 were treated with D-g-PAA/ZnO NPs. The expression of Bax, Bcl-2, p53 and Ki-67 was studied using immunocytochemical analysis. Cytomorphological changes in cells were detected after their incubation with nanocomposites for 24 h. The treatment with D-g-PAA/ZnO NPs caused the increase in the Bax and p53 and the decrease in Ki-67 and Bcl-2 expression. Morphological changes associated with apoptosis were registered: decrease in cell size, appearance of cytoplasmic vacuolation, condensation of chromatin, blebbing. Treatment with D-g-PAA/ZnO nanocomposite led to the initiation of apoptotic cell death in prostate cancer cells in vitro.


Automatic identification of terpenoid skeletons by feed-forward neural networks.
Feed-forward neural networks (FFNNs) were used to predict the skeletal type of molecules belonging to six classes of terpenoids. A database that contains the 13C NMR spectra of about 5000 compounds was used to train the FFNNs. An efficient representation of the spectra was designed and the constitution of the best FFNN input vector format resorted from an heuristic approach. The latter was derived from general considerations on terpenoid structures.


Lactate dehydrogenase, isoenzyme patterns and cation levels in human breast gross cyst fluid.
In order to investigate the diagnostic and/or prognostic value of total activity and isoenzymatic patterns of lactate dehydrogenase, 24 human breast gross cystic fluids were studied. A comparison of total lactate dehydrogenase activity to the serum level revealed an increased activity in about 63% of the cases examined; moreover, a significant increase in the slow-moving lactate dehydrogenase 4 and 5 isoenzymes was observed in some cyst fluids. The levels of Na+ and K+ concentrations were also analyzed and two classes of cysts were identified: one presenting Na+ and K+ levels similar to those found in extracellular compartment; the other with high K+ and low Na+ levels, characteristic of an intracellular fluid. This latter pattern could indicate an active metabolism of the epithelial cells lining the cysts. This breast cyst fluid also showed increased levels of lactate dehydrogenase 4 and 5 isoenzymes. The correlation between an increased activity of lactate dehydrogenase 4 and 5 isoenzymes and high K+ and low Na+ levels could be the expression of a high biosynthetic activity and of an anaerobic metabolism in some cysts, suggesting the evolution of the breast gross cyst lesion to malignancy. The importance of these observations is discussed.


Association of blood pressure variability and neurocognition in children with chronic kidney disease.
Children with chronic kidney disease (CKD) and hypertension have increased blood pressure variability (BPV), which has been associated with lower neurocognitive test scores in adults. Children with CKD are at risk for decreased neurocognitive function. Our objective was to determine whether children with CKD and increased BPV had worse performance on neurocognitive testing compared with children with CKD and lower BPV. This was a cross-sectional and longitudinal analysis of the relation between BPV and neurocognitive test performance in children ≥6 years enrolled in the Chronic Kidney Disease in Children (CKiD) study. Visit-to-visit BPV was assessed by the standard deviation of visit BPs (BPV-SD) and average real variability (ARV). Ambulatory BPV was assessed by SD of wake and sleep periods on 24-h ambulatory BP monitoring. We assessed 650 children with a mean follow-up period of 4.0 years. Children with systolic visit-to-visit BPV in the upper tertile had lower scores on Delis-Kaplan Executive Function System (D-KEFS) Verbal Category Switching than those with BPV in the lower tertile (BPV-SD, 8.3 vs. 9.5, p = 0.006; ARV, 8.5 vs. 9.6, p = 0.02). On multivariate analysis, the association between lower Category Switching score and increased BPV remained significant after controlling for mean BP, demographic characteristics, and disease-related variables [BPV-SD, β = -0.7, 95 % confidence interval (CI) -1.28 to -0.12; ARV, β = -0.54, CI -1.05 to -0.02). Ambulatory BPV was not independently associated with any cognitive measure. Higher systolic visit-to-visit BPV was independently associated with decreased D-KEFS Category Switching scores in children with mild-to-moderate CKD.


Comparative outcomes of lung volume reduction surgery and lung transplantation: a systematic review and meta-analysis.
Lung volume reduction (LVR) and lung transplantation (LTx) have been used in different populations of chronic obstructive pulmonary disease (COPD) patients. To date, comparative study of LVR and LTx has not been performed. We sought to address this gap by pooling the existing evidence in the literature. An electronic search was performed to identify all prospective studies on LVR and LTx published since 2000. Baseline characteristics, perioperative variables, and clinical outcomes were extracted and pooled for meta-analysis. The analysis included 65 prospective studies comprising 3,671 patients [LTx: 15 studies (n=1,445), LVR: 50 studies (n=2,226)]. Mean age was 60 [95% confidence interval (CI): 58-62] years and comparable between the two groups. Females were 51% (95% CI: 30-71%) in the LTx group vs. 28% (95% CI: 21-36%) in LVR group (P=0.05). Baseline 6-minute walk test (6MWT) and pulmonary function tests were comparable except for the forced expiratory volume in 1 second (FEV1), which was lower in the LTx group [21.8% (95% CI: 16.8-26.7%) vs. 27.3% (95% CI: 25.5-29.2%), P=0.04]. Postoperatively, both groups experienced improved FEV1, however post-LTx FEV1 was significantly higher than post-LVR FEV1 [54.9% (95% CI: 41.4-68.4%) vs. 32.5% (95% CI: 30.1-34.8%), P<0.01]. 6MWT was also improved after both procedures [LTx: 212.9 (95% CI: 119.0-306.9) to 454.4 m (95% CI: 334.7-574.2), P<0.01; LVR: 286 (95% CI: 270.2-301.9) to 409.1 m (95% CI: 392.1-426.0), P<0.01], however, with no significant difference between the groups. Pooled survival over time showed no significant difference between the groups. LTx results in better FEV1 but otherwise has comparable outcomes to LVR.


What does social media have to do with health? A case study of Bangkok youths.
This qualitative research aims to understand how Bangkok youths perceive social media usage effects on their physical, psychological, social and spiritual health. A total of 74 Bangkok youths, aged 15-24 years old, divided according to each age and gender group participated in in-depth interviews and mobile phone search observations. Health impact was categorized into the four health aspects through content analysis according to sociological perspectives. Bangkok youths view social media to have both positive and negative effects on their health. Increased awareness of negative results was shown with increased age. While younger youths use social media for entertainment, older youths also use social media for self-development. Interests and degree of sensitivity varied among the genders. Effective health education can only be achieved through future youth-centered research on social media usage based on age, gender and cultural variations.


Assessment of perchlorate-reducing bacteria in a highly polluted river.
A 1-year monitoring experiment of the Sarno River basin was conducted during 2008 to evaluate the overall quality of the water over time and to compare the results with those obtained previously. The physico-chemical and microbiological characteristics of the water course had not changed appreciably with respect to previous determinations, thus emphasizing the major contribution of untreated urban wastewater to the overall pollution of the river. Moreover, attention was paid to the perchlorate ion, one of the so-called emerging contaminants, which is widespread in natural environments and is known to have adverse effects on the human thyroid gland. Over the entire monitoring program, we did not find appreciable levels of perchlorate, although the particular environmental condition could support its development. Thus, a dedicated study was designed to assess the presence of bacteria that can reasonably reduce perchlorate levels. By enrichment and molecular procedures, we identified α- and β-Proteobacteria strains, classified by 16S rDNA sequences as Dechlorospirillum sp. and Dechlorosoma sp., respectively. Further physiologic characterization and the presence of the alpha subunit gene (pcrA) of the perchlorate reductase in both strains confirmed the presence in the river of viable and active perchlorate dissimilatory bacteria.


On the possible involvement of ascorbic acid and copper proteins in leukemia: II. Electron spin resonance (ESR) and atomic absorption investigations on erythrocyte ghosts and plasma.
The effect of ascorbic acid on white ghosts of erythrocytes and plasma has been investigated by means of ESR spectroscopy. Since the spectra obtained are identical to the one obtained with leukemic blood it is concluded that the receptor for vitamin C has to be searched for in membrane and plasma as well. Determination of Cu and Fe by means of atomic absorption spectroscopy revealed that both of the metals are also present in the membrane. In the case of copper, it must exist there as a protein which has not been identified yet. Oxidizing substances, such as KMnO4, reverse the effect produced by ascorbic acid.


Rapid dual-echo ramped hybrid encoding MR-based attenuation correction (dRHE-MRAC) for PET/MR.
In this study, we propose a rapid acquisition for MR-based attenuation correction (MRAC) in positron emission tomography (PET)/MR imaging, in which an ultrashort echo time (UTE) image and an out-of-phase echo image are obtained within a single rapid scan (35 s) at high spatial resolution (1 mm3 ), which allows accurate estimation of a pseudo CT image using 4-class tissue classification (discrete bone, discrete air, continuous fat, and continuous water). In dual-echo ramped hybrid encoding (dRHE), a UTE echo is directly followed by a second out-of-phase echo, in which hybrid spatial encoding combining single-point imaging and 3-dimensional radial frequency encoding is used to improve the quality of both images. Two-point Dixon reconstruction is used to estimate fat- and water-separated images, and UTE images are used to estimate bone. Air and bone segmentation is improved by using multiple UTE images with an advanced hybrid-encoding scheme that allows reconstruction of multiple UTE images. To evaluate the proposed method, dRHE-MRAC PET/MR brain imaging was performed in 10 subjects. Dice coefficients and PET reconstruction errors relative to CT-based attenuation correction were compared with existing system MRAC approaches. In dRHE-MRAC, the Dice coefficients for soft tissue, air, and bone were respectively 0.95 ± 0.01, 0.62 ± 0.06, and 0.78 ± 0.05, which was a significantly improved result compared with existing approaches. In most brain regions, dRHE-MRAC showed significantly reduced PET error (less than 1%) with P values less than 0.05. Dual-echo ramped hybrid encoding enables rapid and robust imaging for MRAC with a very rapid acquisition. Magn Reson Med 79:2912-2922, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Adherence to the healthy lifestyle guideline in relation to the metabolic syndrome: Analyses from the 2013 and 2018 Indonesian national health surveys.
In this study, we aimed to investigate differences in lifestyle factors and prevalence of metabolic syndrome (MetS) in the Indonesian population between 2013 and 2018. In addition, we investigated whether adherence to the 2015-released national healthy lifestyle guideline ('GERMAS') is associated with MetS in different sex, age, urban/rural, and BMI categories. We performed cross-sectional analyses in individuals aged >15 of the 2013 (n = 34,274) and 2018 (n = 33,786) Indonesian National Health Surveys. A stratified, multi-stage, systematic random sampling design and the probability proportional to size method were used to select households in the 34 provinces across the country. MetS was defined according to the Joint Interim Statement Criteria, and adherence to 'GERMAS' guideline was defined as fulfilling the national healthy lifestyle recommendations of ≥150 min/week physical activity (PA), ≥5 portions/day fruit and vegetable (FV), no smoking (NS), and no alcohol consumption (NA). We examined the associations of each lifestyle factor with MetS using logistic regression categorised by sex, age groups, urban/rural, and BMI, and adjusted for sociodemographic factors. We observed that men who adhered to the guideline had lower odds ratio of MetS [OR(95%CI) associated with PA: 0.85(0.75-0.97); NA: 0.75(0.56-1.00)] than non-adherent men. Middle-aged adults who adhered to the guideline had lower OR of MetS [PA: 0.85(0.72-1.01); FV: 0.78(0.62-0.99); NA: 0.66(0.46-0.93)] than non-adherent adults <45 years. The adherent urban population had lower OR of MetS [FV: 0.85(0.67-1.07); NA: 0.74(0.52-1.07)] than the non-adherent urban population. Those with overweight or obesity who adhered to the guideline had relatively lower odds of MetS than those who did not. In conclusion, in this nationally representative study, adherence to the 'GERMAS' guideline may confer cardiometabolic health benefits to several groups of the Indonesian population, particularly men, middle-aged, those with overweight and obesity, and potentially urban population.


Nucleolar organizer regions in adenoid cystic carcinoma of the salivary glands.
In this study of proliferative activity of adenoid cystic carcinomas (ACCs) with different histological patterns, the argyrophilic staining method of nucleolar organizer regions (AgNORs) was applied to paraffin sections from 25 tumors. Sixteen of the neoplasms showed a mixture of different histological patterns in the same section. The AgNOR numbers in the different histological pattern areas in the same tissue sections of all 16 tumors were lowest in the cribriform, intermediate in the trabecular, and highest in the solid pattern areas. The mean AgNOR number was highest in the solid pattern (3.33 +/- 0.52), and lowest in the cribriform pattern (2.12 +/- 0.43). The results show the order of proliferative activity in the different histological pattern areas of ACC, and explain the previous clinical finding that the prognosis of ACC is poorest in solid pattern ACCs. AgNOR staining appears to be a useful technique for evaluation of the proliferative activity of each histological pattern area of ACC, especially when there are different histological pattern areas in the same tissue section.


Suboccipital steroid injections for transitional treatment of patients with more than two cluster headache attacks per day: a randomised, double-blind, placebo-controlled trial.
Suboccipital steroid injections can be used for preventive treatment of cluster headache but few data are available for the efficacy of this approach in clinical trials. We aimed to assess efficacy and safety of repeated suboccipital injections with cortivazol compared with placebo as add-on therapy in patients having frequent daily attacks. In our randomised, double-blind, placebo-controlled trial at the Emergency Headache Centre in Paris, France, we enrolled adults aged 18-65 years with more than two cluster headache attacks per day. We randomly allocated patients to receive three suboccipital injections (48-72 h apart) of cortivazol 3·75 mg or placebo, as add-on treatment to oral verapamil in patients with episodic cluster headache and as add-on prophylaxis for those with chronic cluster headache, on the basis of a computer-generated list (blocks of four for each stratum). Injections were done by physicians who were aware of treatment allocation, but patients and the evaluating physician were masked to allocation. The primary outcome was reduction of the number of daily attacks to a mean of two or fewer in the 72 h period 2-4 days after the third injection. We assessed all patients who received at least one dose of study drug in the intention-to-treat analysis. This study is registered with ClinicalTrials.gov, number NCT00804895. Between November, 2008, and July, 2009, we randomly allocated 43 patients (15 with chronic and 28 with episodic cluster headache) to receive cortivazol or placebo. 20 of 21 patients who received cortivazol had a mean of two or fewer daily attacks after injections compared with 12 of 22 controls (odds ratio 14·5, 95% CI 1·8-116·9; p=0·012). Patients who received cortivazol also had fewer attacks (mean 10·6, 95% CI 1·4-19·9) in the first 15 days of study than did controls (30·3, 21·4-39·3; mean difference 19·7, 6·8-32·6; p=0·004). We noted no serious adverse events, and 32 (74%) of 43 patients had other adverse events (18 of 21 patients who received cortivazol and 14 of 22 controls; p=0·162); the most common adverse events were injection-site neck pain and non-cluster headache. Suboccipital cortivazol injections can relieve cluster headaches rapidly in patients having frequent daily attacks, irrespective of type (chronic or episodic). Safety and tolerability need to be confirmed in larger studies. None.


NIR II light response-based PDA/AuPt@CuS composites: Simultaneous readout of temperature and pressure sensing strategy for portable detection of pathogenic bacteria.
In this study, we developed a simultaneous readout of pressure and temperature dual-signals platform based on the second near-infrared (NIR II) light response-based polydopamine (PDA)-functionalized-AuPt nanoparticles (NPs)@CuS nanosheets (PDA/AuPt@CuS NS) composite. Due to the excellent NIR photothermal performance of PDA/AuPt@CuS NS, it contribute to the decomposition of H2O2 and NH4HCO3 to generate gases (including O2, CO2, and NH3) can be promoted, which can amplify the pressure signals in a sealed container. A sandwich mode is formed between Fe3O4 NPs and PDA/AuPt@CuS NS based on the dual-aptamer when target pathogenic bacteria is present. And, it is possible to convert the molecular recognition signals between the dual-aptamers into amplified pressures and temperatures, which can be read out by a portable pressure meter and smartphones simultaneously. It may offer the possibility for quantitative POCT analysis of Pathogenic Bacteria. Moreover, because of the high photothermal efficiency of this method, the developed dual-mode method can achieve that following the detection of bacteria and killing them immediately. As a result, secondary contamination is eliminated and bacterial transmission is avoided. The developed dual-signal sensing platform is also inexpensive, simple to operate and rapidly, indicating that it can be used for food safety analysis, clinical applications, and environmental monitoring.


Darinaparsin: First Approval.
Darinaparsin (Darvias®), an organoarsenic drug, is a novel mitochondrial-targeted anticancer agent currently being developed by Solasia Pharma K.K for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL). An intravenous formulation of darinaparsin has been approved for the treatment of relapsed or refractory PTCL in Japan, and preparation for the next stage of the clinical development program for this indication is currently underway in China, the USA and the EU. This article summarizes the milestones in the development of darinaparsin leading to this first approval for relapsed or refractory PTCL.


Old and new tools to dissect calcineurin's role in pressure-overload cardiac hypertrophy.
In the last several years, a number of experiments have implicated a pivotal role of the calcium/calmodulin-calcineurin dependent pathway as a final common signaling mechanism by which diverse hypertrophic stimuli converge to mediate hypertrophic responses in cardiomyocytes. Calcineurin inhibitors, i.e. cyclosporine A (CsA) and FK506, can interrupt the pathway, thereby preventing cardiac hypertrophy. The data that convincingly support this novel hypothesis were derived either from in vitro studies in cultured cardiomyocytes or from in vivo studies in transgenic mice. However, when the hypothesis was tested in clinically relevant animal models of cardiac hypertrophy, controversial results and conclusions emerged. In conventional models of cardiac hypertrophy, two questions remain to be answered: (1) whether calcineurin is activated in hypertrophied cardiac muscle, and (2) whether calcineurin inhibitors prevent cardiac hypertrophy. In addition, clinical observations have revealed that calcineurin inhibitors appear to exert pro-hypertrophic effects in organ transplant recipients. The controversies suggest that current calcineurin inhibitors are blunt tools for testing the hypothesis in pressure-overload hypertrophy in vivo, because there are so many confounding effects that are associated with systemic administration of the drugs. As such, new genetic approaches may overcome some of the problems associated with pharmacological inhibitors. This invited review will focus on the controversies surrounding the ability of calcineurin inhibition to prevent conventional (pressure-overload) cardiac hypertrophy and the new genetic approaches to address the question.


Comparison of chicken erythroid cell nuclear isolation methods using morphological, immunochemical and biochemical criteria.
Chicken erythroid nuclei were prepared using four published methods. Our findings indicate that nuclei prepared by nitrogen cavitation are less likely to be contaminated with plasma membrane fragments than those made by procedures involving cell disruption by hypotonic lysis. However, globin gene sequences were much less sensitive to DNase I digestion in nuclei prepared by nitrogen cavitation. This suggests that the conformation of chromatin was altered by the cavitation procedure. Analysis of the proteins solubilized during limited DNase I digestion of nuclei prepared by both hypotonic lysis and cavitation revealed no appreciable differences in HMG proteins but a notable difference in the RNP-associated proteins and core histones.


Association of vitamin D deficiency and vitamin D receptor (VDR) gene single-nucleotide polymorphism (rs7975232) with risk of preeclampsia.
Preeclampsia has a multifactorial-yet-elusive etiology. Recent reports suggest a link between preeclampsia and vitamin D (VD) metabolic axis. Genetic variations like single-nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) gene can alter the metabolic role of VD, which have been shown by several genetic association studies. However, there is discordance among these studies. The current study aimed to investigate the association of VDR gene polymorphism (ApaI) and VD deficiency with risk of developing preeclampsia. In this case-control study, 40 preeclamptic and 40 normotensive pregnant women were compared for VD status and VDR gene polymorphism. Serum 25-hydroxyvitamin-D [25(OH) D] level was determined by enzyme-linked immunosorbent assay (ELISA) and VDR gene polymorphism Apa1 was analyzed by Allele specific polymerase chain reaction (AS-PCR) using sequence specific primers. Serum levels of 25(OH) D were very low but comparable in both preeclamptic and normotensive pregnant women. The difference between the two groups were not statistically significant (p = .423). VDR gene polymorphism ApaI (rs7975232) was found not to have significant association with the risk of developing preeclampsia. The frequencies of wild genotype (GG) in preeclamptic and normotensive women were 27.5% and 22.5% respectively. A total of 25% of preeclamptic women had mutant homozygous genotype (TT) and 17.5% of normotensive women had mutant homozygous genotype. The frequency of mutant heterozygous genotype (GT) in preeclamptic patients was 47.5% and in normotensive women was 60%. The variation of wild and mutant genotypes between the two groups was not statistically significant (p > .05). This study showed that VDR gene polymorphism (ApaI) and VD deficiency are not associated with the risk of preeclampsia.


Antigen-specific targeting and elimination of EBV-transformed B cells by allergen toxins.
With the exception of antigen-specific immunotherapy, current treatments for atopic diseases provide only symptomatic relief. Because of the increasing incidence of such diseases, the development of novel strategies and concepts for the treatment of allergies is urgently needed. Here we present a new approach for the treatment of atopic diseases. The strategy is comparable to the application of immunotoxins in cancer therapy, in which a cytotoxic peptide is coupled to a cancer cell-specific antibody fragment or ligand. In the case of so-called allergen toxins (ATs), the target cell-specific moiety is an allergen or allergen-derived fragment, which should be bound only by allergen-reactive cells. After receptor-mediated internalization, allergen-specific cells are killed, and the allergic pathogenesis is interrupted. Proof of the AT principle was shown by using a human ex vivo system in which EBV was used to transform human B cells specific for the timothy grass pollen allergen Phl p 5b. The AT is composed of the major B-cell and T-cell epitopes of the Phl p 5b (P5) allergen fused to a truncated form of the highly toxic Pseudomonas aeruginosa exotoxin A (ETA'). Allergen-specific and nonspecific B cells were challenged with P5-ETA', but only the Phl p 5b-reactive B cells showed selective binding and cytotoxicity. This approach represents an initial step toward a novel therapeutic strategy in the treatment of atopic diseases.


Small airway disease associated with Sjögren's syndrome: clinico-pathological correlations.
Relationships among clinical, physiological, imaging and pathological findings of small airway disease associated with Sjögren's syndrome have remained unclear. We retrospectively studied 14 patients who underwent surgical lung biopsy and who were diagnosed with small airway disease associated with primary or secondary Sjögren's syndrome. We compared clinical, bronchoalveolar lavage, physiological, imaging and pathological findings between primary and secondary Sjögren's syndrome. We scored HRCT and pathological abnormalities and investigated correlations among physiological, HRCT and pathological data, changes in physiological parameters and in HRCT scores after two years of treatment, as well as correlations between these values and pathological scores. Bronchoalveolar lavage fluid, physiological, imaging and pathological findings of the airways did not significantly differ between primary and secondary Sjögren's syndrome. Air trapping on HRCT negatively correlated with MEF50 and MEF25. Although lymphoid cell infiltration and peribronchiolar fibrosis were the most common pathologies, constrictive change scores correlated negatively with MEF50 and MEF25, positively with air trapping scores and negatively with improvements after therapy in MEF(50), MEF(25) and air trapping. Constrictive change was the most significant determinant of physiological and imaging presentations and of changes in these factors after therapy for small airway disease associated with Sjögren's syndrome.


The returns to early-life interventions for very low birth weight children.
We use comprehensive administrative data from Rhode Island to measure the impact of early-life interventions for low birth weight newborns. Our analysis relies on a regression discontinuity design based on the 1,500 g threshold for Very Low Birth Weight (VLBW) status. We find that threshold crossing causes more intense in-hospital care, in line with prior studies. In terms of later-life outcomes, we show that threshold crossing causes a 0.34 standard deviation increase in test scores in elementary and middle school, a 17.1 percentage point increase in the probability of college enrollment, and a $66,997 decrease in social program expenditures by age 14.


Successful palliation by pulmonary artery banding in absent pulmonary valve syndrome with aneurysmal pulmonary arteries.
Three infants with absent pulmonary valve syndrome were treated between 1977 and 1980. All infants were in critical cardiorespiratory failure refractory to medical therapy. Pulmonary artery banding was performed to reduce the volume occupied by the large pulsating pulmonary artery in a limited mediastinal space. The band reduced tracheobronchial compression and increased effective cardiac output. All three infants survived the procedure and, at follow-up, significant improvement in cardiorespiratory function has been noted, with satisfactory growth. This experience suggests that pulmonary artery banding has a place in the initial management of absent pulmonary valve syndrome, allowing survival so that total correction can be undertaken more safely at a later stage.


First detection of Rickettsia conorii ssp. caspia in Rhipicephalus sanguineus in Zambia.
Ticks are important vectors for Rickettsia spp. of the spotted fever group all around the world. Rickettsia conorii is the etiological agent of boutonneuse fever in the Mediterranean region and Africa. Tick identification was based on morphological features and further characterized using the 16S rRNA gene. The ticks were individually tested using pan-Rickettsia real-time-PCR for screening, and 23S-5S intergenic spacer region, 16S rDNA, gltA, sca4, ompB, and ompA genes were used to analyze the Rickettsia positive samples. Rickettsia conorii ssp. caspia was detected in tick collected in Zambia for the first time, thus demonstrating the possibility of the occurrence of human disease, namely Astrakhan fever, due to this Rickettsia ssp. in this region of Africa. The prevalence of R. conorii ssp. caspia was 0.06% (one positive tick out of 1465 tested ticks) and 0.07% (one positive tick out of 1254 tested Rh. sanguineus).


Nutritional management in the child with epidermolysis bullosa.
Children with dystrophic forms of epidermolysis bullosa and oropharyngeal lesions often evidence the features of chronic malnutrition. Nutritional assessment plays a key role in the long-term management of these patients.


Management of pediatric asthma at home and in school.
The incidence of pediatric asthma in the United States creates a huge financial burden to the economy as well as a negative impact on child health. Identification and elimination of asthma triggers are helpful in reducing asthma exacerbations. The incidence of asthma is higher in African American and underserved populations. Improved management of pediatric asthma leads to improved school performance, improved mental health, and general well-being.


Arthroscopic surgery of the metatarsophalangeal first joint.
Arthroscopic surgery of the metatarsophalangeal first joint was used to treat a dorsal impingement syndrome of the hallux by removing the dorsally located osteophytes. Also, osteochondritis dissecans, painful sesamoid bones resistant to conservative therapy, and hallux rigidus were arthroscopically treated in a prospective study enrolling 24 consecutive patients. Seventeen patients were high-level athletes. Pain, swelling, sports, and work involvement were recorded. The operative technique is described. There was one persistent loss of sensitivity of the hallux. In the dorsal impingement group, 8 of 12 patients had a good or excellent result after a minimum follow-up of 2 years. In patients with osteochondritis dissecans, 3 of 4 showed good or excellent results. In hallux rigidus and sesamoid bone removal the results were less favorable. As in all arthroscopic procedures there was a fast rehabilitation and work resumption. Especially in athletes arthroscopically, treatment of a dorsal impingement syndrome or osteochondritis dissecans can be recommended because of the diminished chance of scar fibrosis.


A therapeutic regimen for 3-hydroxyisobutyryl-CoA hydrolase deficiency with exercise-induced dystonia.
3-Hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency is a recently described disease resulting from mutations in HIBCH with no effective treatment. Here, we report a female Chinese patient presenting with exercise-induced dystonia and bilateral symmetrical hyperintensities of the globus pallidus on brain MRI associated with novel HIBCH mutations (c.1027C>G;p. H343D and c.383T>A;p.V128D). After treatment for 1 year with a low-valine diet, both clinical symptoms and brain lesions improved substantially. We propose that HIBCH deficiency should be considered in the differential diagnosis for patients with exercise-induced dystonia, particularly if bilateral symmetrical lesions in the globus pallidus are present. A low-valine diet is a potentially promising treatment for HIBCH deficiency.


Pan-genome: A promising resource for noncoding RNA discovery in plants.
Plant genomes contain both protein-coding and noncoding sequences including transposable elements (TEs) and noncoding RNAs (ncRNAs). The ncRNAs are recognized as important elements that play fundamental roles in the structural organization and function of plant genomes. Despite various hypotheses, TEs are believed to be a major precursor of ncRNAs. Transposable elements are also prime factors that cause genomic variation among members of a species. Hence, TEs pose a major challenge in the discovery and analysis of ncRNAs. With the increase in the number of sequenced plant genomes, it is now accepted that a single reference genome is insufficient to represent the complete genomic diversity and contents of a species, and exploring the pan-genome of a species is critical. In this review, we summarize the recent progress in the field of plant pan-genomes. We also discuss TEs and their roles in ncRNA biogenesis and present our perspectives on the application of pan-genomes for the discovery of ncRNAs to fully explore and exploit their biological roles in plants.


A self-controlled trial to evaluate the use of active hearing defenders in the engine rooms of operational naval vessels.
Active Hearing Defenders are established hearing protectors with in-built electro-acoustics that shut-off ambient noise while allowing effective communication between users. A blinded, self-controlled trial was conducted among naval servicemen to compare the effectiveness of two types of active hearing defenders (Howard-Leight Thunder TM and COM-55) in relation to passive hearing defenders in an operational environment. Subjects felt that the active hearing defenders were more comfortable, durable, and that the active hearing defenders helped them work better. When subjects were tested with a speech discrimination battery (Central Institute of the Deaf, Spondee Word lists), there was a significant difference (p value of 0.04, using the Kruskall-Wallis ANOVA test) between the two active and the passive defenders. However, no significant difference was found between the two types of active hearing defenders. Active hearing defenders are an acceptable and efficacious means of hearing protection in noisy environments.


BeachLog: A multiple uses and interactive beach picture.
There are some tools in place that classifies and/or rank beaches according to a series of parameters. It is possible to identify a gap in the development of tools that map and describe beaches without putting the results into a classification status of good or bad. Since beaches are important from different points of views such as ecology, tourism, economy, pollution or invasive species studies and management, fisheries, estate development, protected areas, among others it is relevant to describe and understand parameters in detail. This work offers a multi-purpose and interactive beach descriptor called BeachLog. It can be used by beachgoers to keep their own records in the same way a diver uses a Diver's LogBook, managers can use the tool to support coastal management projects, long-term monitoring, and beach description baseline. Also, BeachLog can be a didactic tool to aiming to bring environmental sciences closer to technology through the use of spreadsheets and dashboards. BeachLog is based on the more frequent parameters in the literature, selected, organized, accounted for, and altered/added according to expert opinion. We created a list of 28 parameters, all of which were described in details of what is expected to be observed by the user. They were divided into 5 groups (Environmental characteristics, Services & Infrastructure, Information & Security, Planning & Management, and Descriptive). Here, we describe 14 Brazilian beaches using the BeachLog by inputting the results as parameters presence or absence (0/1) and descriptives in a table that can be transformed into an interactive dashboard for better/easier visualization. Planning & Management was absent on all 14 beaches studied, pointing out the relevance and gaps in this group. In the other groups it was possible to observe variation in the parameter occurrence, indicating that each beach is different and it is important to observe parameters individually. Beach Litter and Invasive Species parameters from the Environmental characteristics group were present in all beaches. BeachLog showed as an easy way to describe a beach and can be a tool to support diagnosis and understanding of the beach's status.


[Bi-tissular malignant tumors of the lung. 2 cases].
Two new cases of multiple components pulmonary carcinoma are described: a pneumoblastoma and a epitheliosarcoma. Differenciating clinical features and nosological problems are recelled, allowing to discuss the classification of these two observations.


Health and Functioning of Families of Children With Special Health Care Needs Cared for in Home Care, Long-term Care, and Medical Day Care Settings.
To examine and compare child and parent or guardian physical and mental health outcomes in families with children with special health care needs who have medically complex technology-dependent needs in home care, long-term care (LTC), and medical day care (MDC) settings. The number of children requiring medically complex technology-dependent care has grown exponentially. In this study, options for their care are home care, LTC, or MDC. Comparison of child and parent/guardian health outcomes is unknown. Using repeated measures data were collected from 84 dyads (parent/guardian, medically complex technology-dependent child) for 5 months using Pediatric Quality of Life Inventory Generic Core Module 4.0 and Family Impact Module Data analysis: χ(2), RM-ANCOVA. There were no significant differences in overall physical health, mental health, and functioning of children by care setting. Most severely disabled children were in home care; moderately disabled in MDC; children in vegetative state LTC; however, parents perceived children's health across care setting as good to excellent. Parents/guardians from home care reported the poorest physical health including being tired during the day, too tired to do the things they like to do, feeling physically weak, or feeling sick and had cognitive difficulties, difficulties with worry, communication, and daily activities. Parents/guardians from LTC reported the best physical health with time and energy for a social life and employment. Trends in health care policy indicate a movement away from LTC care to care in the family home where data indicate these parents/guardians are already mentally and functionally challenged.


Red Light Treatment in an Axotomy Model of Neurodegeneration.
Red light has been shown to provide neuroprotective effects. Axotomizing the optic nerve initiates retinal ganglion cell (RGC) degeneration, and an early marker of this is dendritic pruning. We hypothesized that 670 nm light can delay axotomy-induced dendritic pruning in the retinal explant. To test this hypothesis, we monitored the effects of 670 nm light (radiant exposure of 31.7 J cm(-2) ), on RGC dendritic pruning in retinal explants from C57BL/6J mice, at 40 min, 8 h and 16 h post axotomy. For sham-treated retinae, area under the Sholl curve, peak of the Sholl curve and dendritic length at 8 h post axotomy showed statistically significant reductions by 42.3% (P = 0.008), 29.8% (P = 0.007) and 38.4% (P = 0.038), respectively, which were further reduced after 16 h by 40.56% (P < 0.008), 33.9% (P < 0.007), 45.43% (P < 0.006), respectively. Dendritic field area was also significantly reduced after 16 h, by 44.23% (P < 0.019). Such statistically significant reductions were not seen in light-treated RGCs at 8 or 16 h post axotomy. The results demonstrate the ability of 670 nm light to partially prevent ex vivo dendropathy in the mouse retina, suggesting that it is worth exploring as a treatment option for dendropathy-associated neurodegenerative diseases, including glaucoma and Alzheimer's disease.


Polybrominated Diphenyl Ethers Quinone Induces NCOA4-Mediated Ferritinophagy through Selectively Autophagic Degradation of Ferritin.
Polybrominated diphenyl ethers (PBDEs) have been detected ubiquitously in biological and environmental samples. Growing epidemiological data suggested the obvious correlation of PBDEs exposure with adverse health outcomes toward human beings, but exact molecular mechanism(s) are limited. Especially, the toxicological information regarding PBDEs metabolites is missing. Thereafter, this study intends to explore unidentified cell death modalities caused by PBDEs reactive quinone-type metabolite, PBDEQ. We found that PBDEQ induces autophagy in an ROS-dependent manner. Interestingly, the results indicated that PBDEQ degraded ferritin and activated a selective autophagy (termed as ferritinophagy) by using NCOA4 as its cargo receptor. These processes may further promote the release of iron and ROS. These results suggested the incidence of ferritinophagy induced by PBDEQ, which may contribute to PBDE exposure-caused diseases and dysfunctions.


Primary Care and Infectious Disease Provider Adherence to HIV Pre-exposure Prophylaxis (PrEP) Prescribing and Monitoring Recommendations.
This study aimed to compare primary care (PC) and infectious diseases (ID) provider adherence to HIV pre-exposure prophylaxis (PrEP) prescribing and monitoring parameters outlined in Centers for Disease Control/Department of Health and Human Services (CDC/DHHS) guidelines. This retrospective cohort analysis from 2017 to 2022 used prescription and laboratory order data to identify patients prescribed PrEP by PC or ID providers. Primary endpoints assessed were adherence to baseline and follow-up HIV monitoring recommendations in the 12 months following the initial PrEP prescription. Secondary endpoints included appropriate PrEP prescription order quantities (≤ 90-day supply), appropriate renal function monitoring, and identification of factors independently associated with follow-up HIV monitoring adherence. Of the 324 eligible patients identified, 112 received PrEP from an ID specialist and 212 from a PC provider. Patients prescribed PrEP from an ID specialist were more likely to have appropriately completed baseline HIV monitoring (OR = 2.56, 95% CI 1.20, 5.47), follow-up HIV monitoring (OR = 1.81, 95% CI 1.08, 3.05), and renal function monitoring (OR = 2.81, 95% CI 1.69, 4.68); The ID group was also more likely to have PrEP prescriptions appropriately authorized for a days' supply of ≤ 90 days (OR = 4.41, 95% CI 2.60, 7.48). Patients receiving PrEP care from ID specialists had better adherence to all assessed PrEP prescribing and monitoring recommendations compared to those receiving care from PC providers.


Modelling the optimal target age group for seasonal influenza vaccination in Japan.
In Japan, the current influenza vaccination programme is targeting older individuals. On the other hand, epidemics of influenza are likely to be mainly driven by children. In this study, we consider the most cost-effective target age group for a seasonal influenza vaccination programme in Japan. We constructed a deterministic compartmental Susceptible-Exposed-Infectious-Recovered (SEIR) model with data from the 2012/13 to 2014/15 influenza seasons in Japan. Bayesian inference with Markov Chain Monte Carlo method was used for parameter estimation. Cost-effectiveness analyses were conducted from public health care payer's perspective. A scenario targeting children under 15 was expected to reduce the number of cases 6,382,345 compared to the current strategy. A scenario targeting elderly population (age over 49 years) was expected to reduce the number of cases 693,206. The children targeted scenario demonstrated negative ICER (incremental cost-effectiveness ratio) value. On the other hand, elderly targeted scenario demonstrated higher ICER value than the willingness to pay (50,000 USD/QALY). A vaccination programme which targets children under 15 is predicted to have much larger epidemiological impact than those targeting elderly.


Identification of potential inhibitors against Alzheimer-related proteins in Cordyceps militaris ethanol extract: experimental evidence and computational analyses.
Laboratory experiments were carried out to identify the chemical composition of Cordyceps militaris and reveal the first evidence of their Alzheimer-related potential. Liquid chromatography-mass spectrometry analysis identified 21 bioactive compounds in the ethanol extract (1-21). High-performance liquid chromatography quantified the content of cordycepin (0.32%). Bioassays revealed the overall anti-Alzheimer potential of the extract against acetylcholinesterase (IC50 = 115.9 ± 11.16 µg mL-1). Multi-platform computations were utilized to predict the biological inhibitory effects of its phytochemical components against Alzheimer-related protein structures: acetylcholinesterase (PDB-4EY7) and β-amyloid protein (PDB-2LMN). In particular, 7 is considered as a most effective inhibitor predicted by its chemical stability in dipole-based environments (ground state - 467.26302 a.u.; dipole moment 11.598 Debye), inhibitory effectiveness (DS¯ - 13.6 kcal mol-1), polarized compatibility (polarizability 25.8 Å3; logP - 1.01), and brain penetrability (logBB - 0.244; logPS - 3.047). Besides, 3 is promising as a brain-penetrating agent (logBB - 0.257; logPS - 2.400). The results preliminarily suggest further experimental attempts to verify the pro-cognitive effects of l(-)-carnitine (7). The online version contains supplementary material available at 10.1007/s13205-023-03714-9.


Dietary soybean enhances Pit-1 dependent pituitary hormone production in iodine deficient rats.
Reports have shown that soybeans are goitrogenic. In the present study, we investigated the effects of a high soybean diet in rats that were fed normal or iodine-deficient chow on the regulation of anterior pituitary hormone production. Iodine deficiency alone resulted in thyroid hyperplasia, reduced serum thyroxine levels, and a tendency towards an increase in serum thyroid stimulating hormone (TSH). The combination of a high soybean and low iodine diet (ID + DS) acted synergistically to induce thyroid hypertrophy, reduce serum thyroxine and tri-iodothyronine, and markedly increase serum TSH. Immunohistochemical analysis revealed that rats fed the ID + DS diet exhibited a marked increase in their number of pituitary TSH, prolactin (PRL), and growth hormone (GH) producing cells. Pituitary transcription factor-1 (Pit-1) which is involved in the expression of the TSH, PRL, and GH genes was also increased in ID + DS fed rats. These results suggest that a diet high in soybean products modulates anterior pituitary hormone production by regulating Pit-1 induction, in iodine-deficient animals.


Skeletal muscle-specific deletion of lipoprotein lipase enhances insulin signaling in skeletal muscle but causes insulin resistance in liver and other tissues.
Skeletal muscle-specific LPL knockout mouse (SMLPL(-/-)) were created to study the systemic impact of reduced lipoprotein lipid delivery in skeletal muscle on insulin sensitivity, body weight, and composition. Tissue-specific insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp and 2-deoxyglucose uptake. Gene expression and insulin-signaling molecules were compared in skeletal muscle and liver of SMLPL(-/-) and control mice. Nine-week-old SMLPL(-/-) mice showed no differences in body weight, fat mass, or whole-body insulin sensitivity, but older SMLPL(-/-) mice had greater weight gain and whole-body insulin resistance. High-fat diet feeding accelerated the development of obesity. In young SMLPL(-/-) mice, insulin-stimulated glucose uptake was increased 58% in the skeletal muscle, but was reduced in white adipose tissue (WAT) and heart. Insulin action was also diminished in liver: 40% suppression of hepatic glucose production in SMLPL(-/-) vs. 90% in control mice. Skeletal muscle triglyceride was 38% lower, and insulin-stimulated phosphorylated Akt (Ser473) was twofold greater in SMLPL(-/-) mice without changes in IRS-1 tyrosine phosphorylation and phosphatidylinositol 3-kinase activity. Hepatic triglyceride and liver X receptor, carbohydrate response element-binding protein, and PEPCK mRNAs were unaffected in SMLPL(-/-) mice, but peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1alpha and interleukin-1beta mRNAs were higher, and stearoyl-coenzyme A desaturase-1 and PPARgamma mRNAs were reduced. LPL deletion in skeletal muscle reduces lipid storage and increases insulin signaling in skeletal muscle without changes in body composition. Moreover, lack of LPL in skeletal muscle results in insulin resistance in other key metabolic tissues and ultimately leads to obesity and systemic insulin resistance.


The in vivo Pig-a gene mutation assay, a potential tool for regulatory safety assessment.
The Pig-a (phosphatidylinositol glycan, Class A) gene codes for a catalytic subunit of the N-acetylglucosamine transferase complex involved in an early step of glycosylphosphatidyl inositol (GPI) cell surface anchor synthesis. Pig-a is the only gene involved in GPI anchor synthesis that is on the X-chromosome, and research into the origins of an acquired genetic disease involving GPI anchor deficiency (paroxysmal nocturnal hemoglobinuria) indicates that cells lacking GPI anchors, or GPI-anchored cell surface proteins, almost always have mutations in the Pig-a gene. These properties of the Pig-a gene and the GPI anchor system have been exploited in a series of assays for measuring in vivo gene mutation in blood cells from humans, rats, mice, and monkeys. In rats, flow cytometric measurement of Pig-a mutation in red blood cells requires microliter volumes of blood and data can be generated in hours. Spontaneous mutant frequencies are relatively low (<5 × 10(-6)) and rats treated with multiple doses of the potent mutagen, N-ethyl-N-nitrosourea, display Pig-a mutant frequencies that are close to the sum of the frequencies produced by the individual exposures. A general observation is that induced mutant frequencies are manifested earlier in reticulocytes (about 2 weeks after treatment) than in total red blood cells (about 2 months after exposure). Based on data from a limited number of test agents, the assay shows promise for regulatory applications, including integration of gene mutation measurement into repeat-dose toxicology studies.


The single NqrB and NqrC subunits in the Na(+)-translocating NADH: quinone oxidoreductase (Na(+)-NQR) from Vibrio cholerae each carry one covalently attached FMN.
The Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR) is the prototype of a novel class of flavoproteins carrying a riboflavin phosphate bound to serine or threonine by a phosphodiester bond to the ribityl side chain. This membrane-bound, respiratory complex also contains one non-covalently bound FAD, one non-covalently bound riboflavin, ubiquinone-8 and a [2Fe-2S] cluster. Here, we report the quantitative analysis of the full set of flavin cofactors in the Na(+)-NQR and characterize the mode of linkage of the riboflavin phosphate to the membrane-bound NqrB and NqrC subunits. Release of the flavin by β-elimination and analysis of the cofactor demonstrates that the phosphate group is attached at the 5'-position of the ribityl as in authentic FMN and that the Na(+)-NQR contains approximately 1.7mol covalently bound FMN per mol non-covalently bound FAD. Therefore, each of the single NqrB and NqrC subunits in the Na(+)-NQR carries a single FMN. Elimination of the phosphodiester bond yields a dehydro-2-aminobutyrate residue, which is modified with β-mercaptoethanol by Michael addition. Proteolytic digestion followed by mass determination of peptide fragments reveals exclusive modification of threonine residues, which carry FMN in the native enzyme. The described reactions allow quantification and localization of the covalently attached FMNs in the Na(+)-NQR and in related proteins belonging to the Rhodobacter nitrogen fixation (RNF) family of enzymes. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).


Temporal aspects of spatial vision in the cat.
Using behavioral techniques, contrast sensitivity for flickering and stationary gratings was measured in ordinary cats. Gratings of low spatial frequency were more easily detected by the cat when temporal modulation was present, but at high spatial frequencies temporal modulation reduced grating visibility. These psychophysical results are consistent with neurophysiological evidence for the existence of two classes of visual cells in the cat, which are distinguishable in terms of their spatio-temporal response properties.


Development prospects of curable osteoplastic materials in dentistry and maxillofacial surgery.
The article presents classification of the thermosetting materials for bone augmentation. The physical, mechanical, biological, and clinical properties of such materials are reviewed. There are two main types of curable osteoplastic materials: bone cements and hydrogels. Compared to hydrogels, bone cements have high strength features, but their biological properties are not ideal and must be improved. Hydrogels are biocompatible and closely mimic the extracellular matrix. They can be used as cytocompatible scaffolds for tissue engineering, as can protein- and nucleic acid-activated structures. Hydrogels may be impregnated with osteoinductors such as proteins and genetic vectors without conformational changes. However, the mechanical properties of hydrogels limit their use for load-bearing bone defects. Thus, improving the strength properties of hydrogels is one of the possible strategies to achieve the basis for an ideal osteoplastic material.


The 1,4-naphthoquinone derivative from Pyrola rotundifolia activates AMPK phosphorylation in C2C12 myotubes.
An aqueous ethanol extract of Pyrola rotundifolia L. induced AMP-activated protein kinase (AMPK) phosphorylation in C2C12 myotubes. The bioassay-guided fractionation of the extract led to the isolation a 2-methyl-7-hydroxymethyl-1,4-naphthoquinone, or a 7'-hydroxy-chimaphilin, which showed concentration-dependent AMPK phosphorylation activity at 2.5-20 μg/ml. At a concentration of 10 μg/ml (50 μM), an approximately four-fold increase in the AMPKα(Thr¹⁷²) phosphorylation level was observed. The stimulatory effect of naphthoquinone on AMPK activity was comparable to that of known compounds found in natural sources that activate the AMPK signaling pathway.


[Influenza vaccine].
The efficacy of seasonal influenza vaccines is not always high. However, this is not due to the vaccine itself, rather due to the viral frequent antigenic changes. Instead of the current chicken embryonated egg-based strategy for vaccine production, the use of the cell culture-based one may increase its productivity as well as efficacy. In addition, pre-pandemic H5N1 vaccines are now being stockpiled worldwide, although their total vaccine doses are limited due to their low productivity and immunogenicity. We need to recognize the importance of the vaccine-based prophylaxis against influenza considering recent prevalence of oseltamivir-resistant viruses such as H1N1 viruses.


Evidence of Non-Linear Associations between Frustration-Related Prefrontal Cortex Activation and the Normal:Abnormal Spectrum of Irritability in Young Children.
Burgeoning interest in early childhood irritability has recently turned toward neuroimaging techniques to better understand normal versus abnormal irritability using dimensional methods. Current accounts largely assume a linear relationship between poor frustration management, an expression of irritability, and its underlying neural circuitry. However, the relationship between these constructs may not be linear (i.e., operate differently at varying points across the irritability spectrum), with implications for how early atypical irritability is identified and treated. Our goal was to examine how the association between frustration-related lateral prefrontal cortex (LPFC) activation and irritability differs across the dimensional spectrum of irritability by testing for non-linear associations. Children (N = 92; ages 3-7) ranging from virtually no irritability to the upper end of the clinical range completed a frustration induction task while we recorded LPFC hemoglobin levels using fNIRS. Children self-rated their emotions during the task and parents rated their child's level of irritability. Whereas a linear model showed no relationship between frustration-related LPFC activation and irritability, a quadratic model revealed frustration-related LPFC activation increased as parent-reported irritability scores increased within the normative range of irritability but decreased with increasing irritability in the severe range, with an apex at the 91st percentile. Complementarily, we found children's self-ratings of emotion during frustration related to concurrent LPFC activation as an inverted U function, such that children who reported mild distress had greater activation than peers reporting no or high distress. Results suggest children with relatively higher irritability who are unimpaired may possess well-developed LPFC support, a mechanism that drops out in the severe end of the irritability dimension. Findings suggest novel avenues for understanding the heterogeneity of early irritability and its clinical sequelae.


[Intraocular pressure after cataract extraction with implantation of an intraocular lens].
The subject of our investigations was the behaviour of the IOP after extracapsular and intracapsular operations with implantation of artificial lenses as well into the anterior as into posterior chamber. The investigations were performed on the material of 395 eyes operated in the years 1985-1988. It was established that after these operations glaucoma is a very rare complication.


Association of Pseudoplacentational Endometrial Hyperplasia and Pyometra in Dogs.
Uterine inflammation is the most common and clinically relevant genital change in bitches. The aim of this study was to evaluate the association between uterine hyperplasic lesions and uterine inflammation. Uteri and ovaries from 200 bitches were sampled after elective or pathological ovariohysterectomy and histologically evaluated. Endometrial hyperplastic lesions were classified as cystic endometrial hyperplasia (CEH) or pseudoplacentational endometrial hyperplasia (PEH), whereas cases of uterine inflammation were subdivided into endometritis or pyometra. The frequency of PEH (79.4%) was significantly higher (P <0.05) than CEH (20.6%), whereas 17.5% of the animals did not have any endometrial hyperplasic lesions. There was a statistically significant association between the frequency of PEH and uterine inflammation (P <0.0001) and PEH was also significantly associated with pyometra (P <0.05). There was no significant association between CEH and uterine inflammation. There was a significant association between dioestrus and the frequencies of PEH, CEH, uterine inflammation and pyometra. However, there was no significant association between endometritis and dioestrus. These results support the recommendation that the terms 'cystic endometrial hyperplasia', 'pseudoplacentational endometrial hyperplasia' and 'pyometra' should be used separately, instead of the classical term 'cystic endometrial hyperplasia-pyometra complex'.


Differential Sensitivity of a Coccal Green Algal and a Cyanobacterial Species to Dissolved Natural Organic Matter (NOM) (8 pp).
and Aim. In non-eutrophicated freshwaters, humic substances (HS) pose chemical stresses on aquatic organisms and, hence, separating sensitive from less sensitive or even tolerant species. One of the stresses, identified so far, is the reduction of photosynthetic oxygen production and reduction in growth in freshwater macrophytes and algae. In a previous paper, it has been shown that even closely related coccal green algae responded differently upon identical stress by HS, which is consistent with the hypothesis above. Due to their much simpler cellular ultrastructure, cyanobacteria are supposed to be more sensitive to HS exposure than eukaryote should be. One coccal green algal species (Desmodesmus communis) and one cyanobacterium (Chroococcus minutus) were exposed to four natural organic matter (NOM) isolates. One NOM has been isolated from a brown water lake (Schwarzer See) in Brandenburg State; three were obtained from a comprehensive Scandinavian NOM research project and originated from Norway (Birkenes), Finland (Hietajärvi), and Sweden (Svartberget). Cultures of D. communis and C. minutus were obtained from the Culture Collection of Algae, Göttingen, and maintained in a common medium. The cultures were non-axenic. The algae and cyanobacteria were exposed under identical conditions to environmentally realistic NOM concentrations. Cell numbers were counted microscopically in Neugebauer cuvettes in triplicates. To avoid limitation by nutrient depletion, the experiments were terminated after 14 to 15 days. Until culture day 12, no growth limitation has been observed in the controls. All NOM isolates modulated the growth of the algae and cyanobacteria. During the early culture days, there was a slight growth promotion with the coccal green alga and to a much lesser degree with the cyanobacterium. Yet, the major effect were significant reductions in cell yield in both primary producer cultures. C. minutus was much more affected than D. communis. This applies particularly to the three tested Scandinavian NOM isolates, which were effective at concentrations even below 1 mg L-1 DOC. The growth promoting effect may be due to an increase in bioavailability of some trace nutrients in the presence of NOM, the release of some growth promoting substances by microbial or photochemical processing of the NOM, and/or a hormetic effect. The growth reducing effect can be explained as a herbicide-like mode of action that affects the photosystem II most prevalent by blocking the electron transport chain, absorption of electrons, or production of an internal oxidative stress after processing the bioconcentrated HS. Furthermore, it may be postulated that also photo-toxicity of these HS in the algal cells contributes to the overall toxicity; however, experimental evidence is lacking so far. Upon exposure to HS, cyanobacteria appear to be much more sensitive than coccal green algae and respond in growth reduction. This high sensitivity of cyanobacteria to HS may explain phytoplankton patterns in the field. Eutrophic, humic-rich lakes do not support the cyanobacterial blooms characteristic of eutrophic, but humic-poor lakes. In the humic-rich systems, raphidophytes or, less frequent, specific coccal greens are more common. Obviously, cyanobacteria appear to be unable to make advantage of their accessory pigments (phycocyanin) to exploit the reddish light prevailing in humic-rich lakes. . At present, no effective structure can be figured out which may be responsible for the adverse effect on the cyanobacterial species. It is reserved to future research whether or not HS may be applied more specifically (for instance, with elevated moieties of the effective structures) as a natural geochemical to combat cyanobacterial blooms.


Two new species of Timea from the Southwest Atlantic (Timeidae, Demospongiae, Porifera).
Comprising 56 species, Timea Gray, 1867 belongs to the monotypic family Timeidae Gray, 1867, with both family and genus characterized by the presence of (sub)tylostyles as megascleres, and euasters as microscleres. Two new species are described from the coast of Rio de Janeiro state, Timea berlincki sp. nov. and Timea clandestina sp. nov., the first of which also from São Paulo state (southeastern Brazil). Both are compared to other species based on their morphological and skeletal characters. Records of all species of the genus worldwide are tabulated and discussed, and an identification key for Tropical western Atlantic species of Timea is offered.


Evaluation of skin thickness lesions in patients with Lyme disease measured by modified Rodnan total skin score.
Recently, a possible etiological connection between infection with Borrelia burgdorferi and various skin lesions, including morphea and systemic sclerosis (SSc), has been discussed. The aim of our study was the evaluation of frequency of skin thickening typical of SSc or morphea in the group of patients with Lyme disease (LD) with frequent exposition to tick bites. The group consisted of 110 patients with LD frequently exposed to tick bites form the northeastern Poland, which is an endemic area for this disease. To measure the skin lesions, the modified Rodnan total skin score (RTSS) was used. In the analyzed group, no skin changes typical of morphea or skin thickening were found. According to RTSS, all patients scored 0 points. Raynaud's phenomenon in all patients was not found. The relationship between scleroderma or morphea and LD is still a matter of controversy. Described by some authors, cases with LD and scleroderma may be associated with co-existence of B. burgdorferi infection with autoimmune process.


Comparison of polypeptides from cultured human fibroblasts and sarcoma cells.
The proteins in cell layers of cultured normal diploid human skin (ES, ER) and lung (WI-38) fibroblasts were compared to those of SV40-transformed human fibroblasts (WI-38/VA-13), human rhabdomyosarcoma (RD) and fibrosarcoma (HT-1080) cells using metabolic amino acid and sugar labeling and surface labeling with tritiated sodium borohydride after oxidation with galactose oxidase. The labeled proteins were analysed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography (fluorography). A transformation-associated decrease in the pericellular glycoprotein fibronectin (subunit molecular weight, 220 000) and in the synthesis of a set of polypeptides in the 130 000--180 000 dalton region was seen. Synthesis of a glycosylated 160 000 dalton polypeptide was markedly reduced. In transformed cells distinct increases of several specific polypeptides was detected in both [35S]methionine and [3H] mannose incorporation experiments but not using the surface labeling method.


ITE Suppresses Angiogenic Responses in Human Artery and Vein Endothelial Cells: Differential Roles of AhR.
Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor is involved in regulation of many essential biological processes including vascular development and angiogenesis. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is an AhR ligand, which regulates immune responses and cancer cell growth. However, the roles of the ITE/AhR pathway in mediating placental angiogenesis remains elusive. Here, we determined if ITE affected placental angiogenic responses via AhR in human umbilical vein (HUVECs) and artery endothelial (HUAECs) cells in vitro. We observed that ITE dose- and time-dependently inhibited proliferation and viability of HUAECs and HUVECs, whereas it inhibited migration of HUAECs, but not HUVECs. While AhR siRNA significantly suppressed AhR protein expression in HUVECs and HUAECs, it attenuated the ITE-inhibited angiogenic responses of HUAECs, but not HUVECs. Collectively, ITE suppressed angiogenic responses of HUAECs and HUVECs, dependent and independent of AhR, respectively. These data suggest that ITE may regulate placental angiogenesis.


Communicating bad news: an integrative review of the nursing literature.
describe how the process of breaking bad news is established and identify how nurses approach the task of giving bad news. integrative review of the literature for articles in Portuguese and English published between 1993-2014, in the databases: Bireme, PubMed, Scopus, Web of Science, CINAHL and Embase. Nine articles were included using the selection flow chart. A digital form was completed for each article according to the Consolidated Criteria for Reporting Qualitative Research checklist and the level of scientific evidence was determined. Of the 99 articles in identified, nine were included after applying the selection flowchart. breaking bad news is frequent in the area of oncology and palliative care, with a strong cultural influence on the autonomy of nurses in this process. the approach and skills of the nurse during this task influences the patient's reaction to the message. The theme is scarce in the literature and merits further investigation. Descrever como se estabelece o processo de comunicação de más notícias e identificar como o enfermeiro pratica a comunicação de más notícias. Revisão integrativa da literatura com artigos em português e inglês referente ao período 1993-2014 nas bases de dados Bireme, PubMed, Scopus, Web of Science, CINAHL e Embase. Elegeram-se nove artigos pelo fluxograma de seleção. Para cada artigo foi preenchida uma ficha eletrônica, elaborado um checklist do Consolidated Criteria for Reporting Qualitative Research e verificado o nível de evidência científica. Foram identificados 99 artigos e incluídos nove pelo fluxograma de seleção. Transmitir más notícias é frequente nas áreas de oncologia e cuidados paliativos, com forte influência cultural na autonomia do enfermeiro nesse processo. O modo e a habilidade do enfermeiro durante a ação influenciarão a reação do paciente acerca da mensagem. O tema é escasso na literatura, necessitando ser explorado.