Analysis of Fatty Acid Metabolism Using Stable Isotope Tracers and Mass Spectrometry.
Cells can synthesize fatty acids by ligating multiple acetyl units from acetyl-CoA. This is followed by desaturation and elongation reactions to produce a variety of fatty acids required for proper cellular functioning. Alternatively, exogenous lipid sources can contribute to cellular fatty acid pools. Here, we present a method based on incorporation of (13)C-carbon from labeled substrates into fatty acids and subsequent mass spectrometry analysis. The resulting labeling patterns can be used to determine (1) (13)C-enrichment of lipogenic acetyl-CoA, (2) the relative contributions of synthesis and uptake, and (3) absolute fatty acid fluxes. We begin by providing a background and general principles regarding the use of stable isotopes to study fatty acid metabolism. We then proceed with detailing procedures for sample preparation and both GC-MS and LC-MS analysis of isotope incorporation. Finally, we discuss the interpretation of the resulting fatty acid-labeling patterns.


Optical and digital image processing in high-resolution electron microscopy.
A comparison is made of the deblurring by digital and optical processing of a single conventional bright field electron image of ferritin particles distributed on a carbon supporting film. The deblurring functions include the effects of the partial temporal and partial spatial coherence of the electron beam, the phase contrast transfer function of the objective lens and Weiner signal to noise optimisation. Practical aspects of the similar results achieved by the two methods are discussed. The relative advantages and disadvantages of the batch and interactive computer modes for picture processing are considered in an Appendix.


Adamantyl tenocyclidines--adjuvant therapy in poisoning with organophosphorus compounds and carbamates.
The objective of this study was to evaluate the efficacy of thienyl phencyclidine (tenocyclidine, TCP) and its newly synthesized adamantyl derivatives containing piperidine (TAPIP), pyrolidine (TAPIR) and morpholine (TAMORF) groups, which were tested with or without standard therapy in mice poisoned with organophosphates (OPs) and carbamates. These compounds with potential activity at the N-methyl- D-aspartate and muscarinic receptors showed low acute toxicity, having LD50 values varying from 106.00 mg/kg (TCP) to >504.00 mg/kg body weight (TAMORF). TCP and its adamantyl derivatives were administered intraperitoneally (2.5 mg/kg body weight) together with atropine (10.0 mg/kg body weight) and with or without 1/4 LD50 of the oxime HI-6. Each compound administered with atropine had a therapeutic effect against poisoning with carbamates propoxur, aldicarb and Ro 02-0683 (protective ratio of tenocyclidines was from 3.99 LD50 of aldicarb to >16.00 LD50 for propoxur). However, the efficacy of those compounds in combination with atropine was lower against poisoning with the OP insecticide dichlorvos (DDVP) and chemical warfare agents soman and tabun. In soman-poisoned mice, the best therapeutic effects were obtained with the combination of HI-6 plus atropine and test compounds, with protective ratios being from 5.40 to 7.12 LD50 of soman. The results suggest that TCP and adamantyl tenocyclidines could be used in combination with atropine as antidotes in carbamate poisoning and as adjuvant therapy to HI-6 and atropine in soman poisoning.


Proliferating cell nuclear antigen in the cytoplasm interacts with components of glycolysis and cancer.
Proliferating cell nuclear antigen (PCNA) is involved in a wide range of functions in the nucleus. However, a substantial amount of PCNA is also present in the cytoplasm, although their function is unknown. Here we show, through Far-Western blotting and mass spectrometry, that PCNA is associated with several cytoplasmic oncoproteins, including elongation factor, malate dehydrogenase, and peptidyl-prolyl isomerase. Surprisingly, PCNA is also associated with six glycolytic enzymes that are involved in the regulation of steps 4-9 in the glycolysis pathway.


Genomic and phylogenetic characteristics of a novel goose astrovirus in Anhui Province, Central-Eastern China.
Goose astrovirus (GAstV) causes a novel disease characterized by urate deposition in the viscera and joints in goslings in many provinces of China, leading to huge economic losses in the goose industry. To better understand the genetic diversity of GAstV in the Anhui Province, Central-Eastern China, 48 kidney samples from goslings with gout were subjected to reverse-transcription polymerase chain reaction (RT-PCR) analysis for detecting GAstV, and phylogenetic analysis of whole genomes and ORFs was performed. Thirty-five samples were GAstV-positive, indicating that the virus is a frequent cause of gout. The whole genomes of 5 GAstV strains were successfully sequenced and named AHAU1-5. The sequenced genomes and those of reference GAstV strains in GenBank displayed 97.4-99.8% similarity. The isolates had high nucleotide sequence similarity with the GAstV reference strain SDPY. A phylogenetic analysis showed that AHAU1 and AHAU4 were closely related to the reference strain SDPY; AHAU2, AHAU3, and AHAU5 formed separate branches. Furthermore, recombination analysis revealed putative recombination sites in the Jiangsu strains that originated from strains in the Anhui and Shandong Provinces, accompanied by the recombination of different strains in the Anhui Province. This study is the first to carry out systematic phylogenetic analysis of GAstV isolated in the Anhui Province, Central-Eastern China. By improving our understanding of the diversity of GAstV in the Anhui Province, these results provide a basis for the prevention and control of its spread.


The non-gastric H,K-ATPase as a tool to study the ouabain-binding site in Na,K-ATPase.
Based on studies with chimeras between (non-)gastric H,K-ATPase and Na,K-ATPase, a model for the ouabain binding site has recently been presented (Qiu et al. J.Biol.Chem. 280 (2005) 32349). In this model, hydrogen bonds between specific amino acid residues of Na,K-ATPase and hydroxyl groups of ouabain play a crucial role. In the present study, a series of ouabain analogues were tested on baculovirus-expressed Na,K-ATPase and an ouabain-sensitive mutant of non-gastric H,K-ATPase (D312E/ S319G/ A778P/ I795L/ F802C). For each analogue, the results obtained by measuring ATPase inhibition and [(3)H]ouabain replacement agreed rather well. In Na,K-ATPase, strophanthidin had a 7-10 times higher and digoxin a 4-12 times lower affinity than ouabain. The results of the non-gastric H,K-ATPase mutant were rather similar to that of Na,K-ATPase with exception of dihydro-ouabain that showed a much lower affinity with the non-gastric H,K-ATPase mutant. Docking studies showed that all analogues bind to the same pocket in Na,K-ATPase. However, the amino acids to which hydrogen bonds were formed differed and depended on the availability of hydroxyl or keto groups in the ouabain analogues.


Recurrent brain metastases.
Metastases of the brain are the most frequent metastatic neurologic complication of systemic cancer and are second only to metabolic encephalopathies as a cause of central nervous system dysfunction in cancer patients. Despite recent significant advances in the diagnosis and treatment of metastases to the brain, many patients will suffer from recurrence. Future advances in the use of chemotherapy, radiosurgery, and newer cancer therapy techniques may lead to further increases in the efficacy of treatment for recurrent brain metastases.


Wheat (Triticum aestivum L.) lipid species distribution in the different stages of straight dough bread making.
Although wheat endogenous lipids strongly impact bread quality, knowledge on their detailed distribution throughout the different stages of straight dough bread making is lacking. We here compared the lipid populations in hexane [containing free lipids (FLs)] and water-saturated butanol extracts [containing bound lipids (BLs)] of wheat flour, freshly mixed and fermented doughs, and bread crumb using high-performance liquid-chromatography [for nonpolar lipids, i.e. mainly free fatty acids (FFA) and triacylglycerols] and electrospray ionization tandem mass spectrometry (for polar lipids). Freshly mixed doughs had lower FL and higher BL levels than flour, a phenomenon referred to as lipid-binding. Furthermore, probably due to the disintegration of flour particles, the overall extractability of nonpolar lipids was higher in freshly mixed dough than in flour. Dough fermentation decreased the extractability of glycolipids, but increased that of nonpolar lipids and phospholipids. We hypothesize that these phenomena result from stretching of the gluten network due to gas cell expansion, which leads to the replacement of some lipids associated with gluten proteins by others. Baking increased the extractability of bound lysophospatidylcholine (LPC) levels, but decreased that of free FFA. This is probably due to in situ dissociation of amylose-LPC inclusion complexes and formation of amylose-FFA inclusion complexes during bread baking and cooling, respectively. The approach and ESI-MS/MS methodology we developed provided valuable insights regarding the distribution of lipids at the different stages of bread making. Hence, it opens perspectives for future efforts to relate differences in lipid composition between wheat cultivars to their bread making quality.


Insertion of nuclear factor-kappaB binding sequence into plasmid DNA for increased transgene expression in colon carcinoma cells.
To increase plasmid DNA (pDNA)-based transgene expression, 5, 10 or 20 repeats of nuclear factor kappaB (NF-kappaB) binding sequences were inserted upstream of the cytomegalovirus (CMV) promoter region of a conventional pDNA encoding firefly luciferase (pCMV-Luc) to obtain pCMV-kappaB5-Luc, pCMV-kappaB10-Luc and pCMV-kappaB20-Luc. Murine carcinoma colon 26 cells, in which NF-kappaB was constitutively activated, were co-transfected with a firefly luciferase-expressing pDNA and a renilla luciferase-expressing pDNA having no NF-kappaB binding sequences using cationic liposomes. The expression efficiency of pCMV-kappaB(n)-Luc was evaluated using the ratio of the luciferase activities. Increasing numbers of NF-kappaB binding sequences significantly increased transgene expression. The expression was increased by NF-kappaB activators and the effects were marked with pDNA having many NF-kappaB binding sequences. These results indicate that insertion of NF-kappaB binding sequences into pDNA is an effective approach to increase transgene expression in cancer cells in which NF-kappaB is activated.


Characteristics of urethral and epididymal semen collected from domestic cats--A retrospective study of 214 cases.
This study was designed to describe and compare basic semen characteristics and sperm motility parameters obtained via computer-assisted sperm analysis (CASA) in feline semen collected from the urethra and epididymis, on the basis of large, unselected population of domestic cats. The semen collected from 214 males was subjected for routine semen assessment and CASA evaluation. Semen collected by urethral catheterization (CT) and by epididymal slicing (EP) has comparable characteristics according to total sperm count (47.7 ± 42.1 and 52.9 ± 45.0), subjective motility (71.1 ± 17.0 and 69.3 ± 13.9), viability (74.9 ± 13.4 and 76.7 ± 10.6), and morphology (52.6 ± 19.0 and 47.2 ± 17.4). The study of a large feline population confirmed a high incidence of teratospermy in cats, which negatively affects sperm motility parameters assessed by CASA. A lack of a correlation between CT and EP semen for total sperm count and viability, as well as occasional gross differences between the morphology of CT and EP semen of the same cat suggests that many factors may affect sperm cells, and the fertility and/or infertility of patients should not be assessed after examining only one sample. Additionally, technical problems with assessment of EP samples (understated results) suggest that CT semen is more appropriate for an analysis by CASA than EP.


Differences in pulsatile and non-pulsatile mechanical circulatory support in long-term use.
Non-pulsatile left ventricular assist device (LVADs) systems have attained more interest for long-term use. We present the results of mechanical circulatory support (MCS) with pulsatile and non-pulsatile LVAD in use in patients for more than 1 year. Between February 1999 and February 2006, 48 patients (mean age, 51; range, 20-72 years) received an LVAD: 24 each had pulsatile (Group A) and non-pulsatile MCS (Group B). Mean support time was 862 days (range, 366-1876 days) in Group A, and 631 days (range 368-1129 days) in Group B. In Group A, 20 patients (80%) were at home for more than 1 year, in Group B, 21 patients (88%). Five VAD-related complications occurred (4 pump exchanges, 1 controller exchange). Echocardiography showed better LV unloading, and the LV end-diastolic diameter was significantly lower in Group A (60 mm) than in Group B (69 mm). Neither the number of driveline/cannula infections nor the number of bleeding and embolic complications differed significantly between groups. Thirty-two patients received heart transplants, 11 died, and 5 still have the VAD. Although echocardiographic data show that pulsatile LVADs seem to better unload the LV, this could not be confirmed by data from right ventricle catheterization. Owing to sufficient LV unloading, longer device durability, less need of anticoagulation therapy, and greater quality of life, non-pulsatile devices are preferred for long-term use. Nevertheless, both systems can be used with good quality of life and an acceptable rate of complications for extended periods of time.


Sepsis Patient Detection and Monitor Based on Auto-BN.
Sepsis is a life-threatening condition caused by an inappropriate immune response to infection, and is a leading cause of elderly death globally. Early recognition of patients and timely antibiotic therapy based on guidelines improve survival rate. Unfortunately, for those patients, it is often detected late because it is too expensive and impractical to perform frequent monitoring for all the elderly. In this paper, we present a risk driven sepsis screening and monitoring framework to shorten the time of onset detection without frequent monitoring of all the elderly. Within this framework, the sepsis ultimate risk of onset probability and mortality is calculated based on a novel temporal probabilistic model named Auto-BN, which consists of time dependent state, state dependent property, and state dependent inference structures. Then, different stages of a patient are encoded into different states, monitoring frequency is encoded into the state dependent property, and screening content is encoded into different state dependent inference structures. In this way, the screening and monitoring frequency and content can be automatically adjusted when encoding the sepsis ultimate risk into the guard of state transition. This allows for flexible manipulation of the tradeoff between screening accuracy and frequency. We evaluate its effectiveness through empirical study, and incorporate it into existing medical guidance system to improve medical healthcare.


Endoscopic carpal tunnel release: a comparison of two techniques with open release.
Proponents of endoscopic carpal tunnel release claim less pain and scar tenderness, quicker recovery of strength, and earlier return to work and daily activities over open methods to release the transverse carpal ligament. This single-center prospective study is the first to compare three different treatment methods: standard open release, a single-portal endoscopic technique (Agee), and a two-portal endoscopic technique (Chow). Two hundred eleven releases in 163 patients were evaluated by clinical outcomes questionnaire and objective testing over a 6-month follow-up period. There was no difference in resolution of paresthesias or nocturnal pain between treatment methods. Patients treated with open release reported more thumb weakness and pain with activities of daily living after surgery. Endoscopically treated patients achieved faster recovery of grip and pinch strength and wrist range of motion. Patients treated endoscopically had less mid-palm tenderness than did patients treated via the open technique, and Agee patients had less distal palmar tenderness than did patients treated via other methods. Overall, and in the workers' compensation group, patients treated endoscopically returned to work sooner. In the non-workers' compensation group, Agree patients returned to work sooner than did patients treated via the other two methods.


The epidemiology of COVID-19 cases and the successful containment strategy in Hong Kong-January to May 2020.
Hong Kong, a Special Administrative Region of China, recorded its first confirmed coronavirus disease 2019 (COVID-19) case on 23 January 2020. We reviewed the case epidemiology and the various public health measures implemented from January to May 2020. The epidemiological and clinical characteristics of the cases recorded in different phases of the epidemic were described and compared, and the effectiveness of the public health measures implemented were reviewed using the changes in the daily number of confirmed cases and the interval from symptom onset to hospital admission. Between January and May 2020, 1084 confirmed COVID-19 cases were reported, about 70% of which had a history of travel during the incubation period. The case fatality ratio was 0.4%. The local epidemic progressed through four phases: (1) preparedness and imported infection from mainland China, (2) local transmission, (3) imported infection from overseas countries associated with local transmission, and (4) controlled imported infection with limited local transmission, with an eventual reduction of the daily case number and minimization of the onset-to-admission interval. Various public health measures, including enhanced surveillance, border control, and social distancing, were introduced in phases in response to the prevailing local and global situations. The overall containment strategy in Hong Kong led to a stabilization of the number of cases and the absence of a community-wide outbreak during the 4.5 m after the first case was reported. This strategy of containment might serve as an example for future planning of preparedness and response against novel infectious agents.


Comparison of CapitalBio™ Mycobacterium nucleic acid detection test and Xpert MTB/RIF assay for rapid diagnosis of extrapulmonary tuberculosis.
The CapitalBio™ Mycobacterium nucleic acid detection test is a real-time fluorescent polymerase chain reaction and TaqMan probe technology test for rapid diagnosis of extrapulmonary tuberculosis (EPTB). This test had moderate sensitivity and high specificity for EPTB, like that of Xpert MTB/RIF, especially for lymph node, chest wall, and purulent fluid samples.


A homozygous frameshift variant in SYCP2 caused meiotic arrest and non-obstructive azoospermia.
Genetic causation for the majority of non-obstructive azoospermia (NOA) remains unclear. Mutations in synaptonemal complex (SC)-associated genes could cause meiotic arrest and NOA. Previous studies showed that heterozygous truncating variants in SYCP2 encoding a protein essential for SC formation, are associated with non-obstructive azoospermia and severe oligozoospermia. Herein, we showed a homozygous loss-of-function variant in SYCP2 (c.2689_2690insT) in an NOA-affected patient. And this variant was inherited from heterozygous parental carriers by natural reproduction. HE, IF, and meiotic chromosomal spread analyses demonstrated that spermatogenesis was arrested at the zygotene stage in the proband with NOA. Thus, this study revealed that SYCP2 associated with NOA segregates in an autosomal recessive inheritance pattern, rather than an autosomal dominant pattern. Furthermore, our study expanded the knowledge of variants in SYCP2 and provided new insight into understanding the genetic etiology of NOA.


Study of binding of low-molecular-weight ligand to biological macromolecules by high-performance liquid chromatography. Evaluation of binding parameters for two drugs bound to human serum albumin.
The binding to a biological macromolecule (human serum albumin, HSA) of small molecules (two drugs: warfarin and furosemide) has been studied by high-performance liquid chromatography. Two methods have been used and compared: frontal analysis and the Hummel and Dreyer methods. The association parameters of each of the two drugs on HSA were determined. The results obtained are in good agreement with those previously published using other techniques. The competition of these two drugs for the same site on HSA has also been shown.


The aetiology of postmenopausal bleeding--a study of 163 consecutive cases in Singapore.
To study the aetiology and pattern of Postmenopausal Bleeding (PMB) in the local population. A retrospective study 163 consecutive patients who presented with postmenopausal bleeding (PMB) SETTING: Kandang Kerbau Hospital, Singapore Malignant causes were found in 42 (25.7%) patients. Cervical carcinoma was the most common malignancy (12.9% of the patients) followed by endometrial carcinoma (11%). Important benign causes are cervicitis (12.9%), atrophic vaginitis (12.3%) and cervical polyp (6.7%). Other benign causes include endometrial hyperplasia (3.1%), urethral caruncle (2.5%) and estrogen replacement therapy (1.8%). PMB is a symptom of varied aetiologies. The associated incidence of malignancy is high and a thorough diagnostic evaluation is mandatory.


[Medical device software requirements and evaluation].
This paper introduces the safety and effectiveness requirements of medical device software. And it discusses the methods on evaluating medical device software from two aspects, the design and development process of the software and software products.


RNA processing and modification protein, carbon catabolite repression 4 (Ccr4), arrests the cell cycle through p21-dependent and p53-independent pathway.
Ccr4d is a new member of the Ccr4 (carbon catabolite repression 4) family of proteins that are implicated in the regulation of mRNA stability and translation through mRNA deadenylation. However, Ccr4d is not believed to be involved in mRNA deadenylation. Thus, its biological function and mechanistic activity remain to be determined. Here, we report that Ccr4d is broadly expressed in various normal tissues, and the expression of Ccr4d is markedly down-regulated during cell cycle progression. We showed that Ccr4d inhibits cell proliferation and induces cell cycle arrest at G(1) phase. Our experiments further revealed that Ccr4d regulates the expression of p21 in a p53-independent manner. Mechanistic studies indicated that Ccr4d strongly bound to the 3'-UTR of p21 mRNA, leading to the stabilization of p21 mRNA. Interestingly, we found that the expression of Ccr4d is down-regulated in various tumor tissues. Collectively, our data indicate that Ccr4d functions as an anti-proliferating protein through the induction of cell cycle arrest via a p21-dependent and p53-independent pathway and suggest that Ccr4d might have an important role in carcinogenesis.


A double-blind comparison of clovoxamine and amitriptyline in the treatment of depressed outpatients.
Forty-two outpatients with major depression were treated in a 4-week double-blind parallel-group comparison of the new antidepressant clovoxamine--a member of oximethers of aralkylketones--with amitriptyline. The two drugs were comparable in efficacy, although because of the small sample size a moderate clinical difference between treatments may not have been detected. The magnitude of unwanted effects also was comparable, but clovoxamine produced fewer "anticholinergic" effects; this was determined by patient complaints of typical anticholinergic symptoms, by decreased salivary flow, and by a new signal detection memory test.


Two mixed-NH3/amine platinum (II) anticancer complexes featuring a dichloroacetate moiety in the leaving group.
Two mixed-NH3/amine platinum (II) complexes of 3-dichoroacetoxylcyclobutane-1, 1-dicarboxylate have been prepared in the present study and characterized by elemental analysis and IR, HPLC-MS and (1)H, (13)C-NMR. The complexes exist in equilibrium between two position isomeric forms and undergo hydrolysis reaction in aqueous solution, releasing the platinum pharmacophores and dichloroacetate which is a small-molecular cell apoptosis inducer. Both complexes were evaluated for in vitro cytotoxic profile in A549, SGC-7901 and SK-OV-3 cancer cells as well as in BEAS-2B normal cells. They exhibit markedly cytotoxicity toward cancer cells by selectively inducing the apoptosis of cancer cells, whereas leaving normal cells less affected. They have also the ability to overcome the resistance of SK-OV-3 cancer cells to cisplatin. Our findings offer an alternative novel way to develop platinum drugs which can both overcome the drug resistance and selectively target tumor cells.


[Multilocular pyoderma gangrenosum : Association with primary manifestation of primary biliary cholangitis].
A 16-year-old female patient with previously diagnosed acne vulgaris was transferred to our clinic in reduced general condition with rapidly progressive and extremely painful ulcerations. In the laboratory exam, inflammatory parameters were highly elevated, but she was normothermic. Based on the findings, we diagnosed multilocular pyoderma gangrenosum. Further investigations established the diagnosis of primary biliary cholangitis as the underlying condition. Treatment with systemic corticosteroids was initiated and we started therapy with ursodeoxycholic acid. This led to improvement within a few days. PAPA-syndrome (pyogenic arthritis, pyoderma gangrenosum and acne vulgaris) could be ruled out by genetic analysis.


Differential interactions of missing in metastasis and insulin receptor tyrosine kinase substrate with RAB proteins in the endocytosis of CXCR4.
Missing in metastasis (MIM), an inverse Bin-Amphiphysin-Rvs (I-BAR) domain protein, promotes endocytosis of C-X-C chemokine receptor 4 (CXCR4) in mammalian cells. In response to the CXCR4 ligand stromal cell-derived factor 1 (SDF-1 or CXCL12), MIM associates with RAS-related GTP-binding protein 7 (RAB7) 30 min after stimulation. However, RAB7's role in MIM function remains undefined. Here we show that RNAi-mediated suppression of RAB7 expression in human HeLa cells has little effect on the binding of MIM to RAB5 and on the recruitment of CXCR4 to early endosomes but effectively abolishes MIM-mediated CXCR4 degradation, chemotactic response, and sorting into late endosomes and lysosomes. To determine whether I-BAR domain proteins interact with RAB7, we examined cells expressing insulin receptor tyrosine kinase substrate (IRTKS), an I-BAR domain protein bearing an Src homology 3 (SH3) domain. We observed that both MIM and IRTKS interact with RAB5 at an early response to SDF-1 and that IRTKS binds poorly to RAB7 but strongly to RAB11 at a later time point. Moreover, IRTKS overexpression reduced CXCR4 internalization and enhanced the chemotactic response to SDF-1. Interestingly, deletion of the SH3 domain in IRTKS abolished the IRTKS-RAB11 interaction and promoted CXCR4 degradation. Furthermore, the SH3 domain was required for selective targeting of MIM-IRTKS fusion proteins by both RAB7 and RAB11. Hence, to the best of our knowledge, our results provide first evidence that the SH3 domain is critical in the regulation of specific endocytic pathways by I-BAR domain proteins.


Transpulmonary thermodilution measurements are not affected by continuous veno-venous hemofiltration at high blood pump flow.
To assess whether continuous veno-venous hemofiltration (CVVH) with high blood pump flow alters the measurements of cardiac index (CI), global end-diastolic volume indexed (GEDVI), and extravascular lung water indexed (EVLWI) performed by transpulmonary thermodilution. Sixty-nine patients were included if they were monitored by a PiCCO2 device and received CVVH through a femoral (n = 62) or an internal jugular (n = 7) dialysis catheter. The blood pump flow was set at 250 mL/min (n = 31) or 350 mL/min (n = 38) and the filtration flow at 6,000 mL/h. A first set of data was collected with a first transpulmonary thermodilution (TD(on)). The blood pump was stopped and the continuous CI derived from pulse contour analysis was recorded (PC(off)). A second data set (TD(off)) was collected before and a last one (TD(on-last)) after restarting the blood pump. [Formula: see text], [Formula: see text], [Formula: see text] , and [Formula: see text] were not significantly different in patients with a femoral dialysis catheter (3.49 ± 0.96, 3.51 ± 0.96, 3.51 ± 0.99, and 3.44 ± 1.00 L min(-1) m(-2), respectively). This was observed with a blood pump flow at 350 mL/min and at 250 mL/min. In these patients with a femoral dialysis catheter, GEDVI did not significantly change when the blood pump was stopped. EVLWI significantly decreased when the blood pump was stopped but to a non-clinically relevant extent (-0.3 ± 0.8 mL/kg). No significant changes in CI, GEDVI, and EVLWI were observed in patients with an internal jugular dialysis catheter over the study period. CVVH with a high blood flow pump does not alter the transpulmonary thermodilution measurements of CI, GEDVI, and EVLWI.


Dead-time correction in dynamic radionuclide studies by computer.
Several methods for the measurement of dead time and for evaluation of the dependencies required to correct dynamic studies for dead-time losses are described. Two program variants were written to produce time-activity curves in the selected areas of interest of the dynamic studies with computer's correction of dead-time losses; these variants are part of the system of programs for complex processing of scintigraphic studies set up for a Clincom instrument. The first variant performs correction on the basis of the registered count rate in the whole image, while the second variant makes us of the additional reference source positioned on the periphery of the camera visual field.


Evaluation of the DAVROS (Development And Validation of Risk-adjusted Outcomes for Systems of emergency care) risk-adjustment model as a quality indicator for healthcare.
Risk-adjusted mortality rates can be used as a quality indicator if it is assumed that the discrepancy between predicted and actual mortality can be attributed to the quality of healthcare (ie, the model has attributional validity). The Development And Validation of Risk-adjusted Outcomes for Systems of emergency care (DAVROS) model predicts 7-day mortality in emergency medical admissions. We aimed to test this assumption by evaluating the attributional validity of the DAVROS risk-adjustment model. We selected cases that had the greatest discrepancy between observed mortality and predicted probability of mortality from seven hospitals involved in validation of the DAVROS risk-adjustment model. Reviewers at each hospital assessed hospital records to determine whether the discrepancy between predicted and actual mortality could be explained by the healthcare provided. We received 232/280 (83%) completed review forms relating to 179 unexpected deaths and 53 unexpected survivors. The healthcare system was judged to have potentially contributed to 10/179 (8%) of the unexpected deaths and 26/53 (49%) of the unexpected survivors. Failure of the model to appropriately predict risk was judged to be responsible for 135/179 (75%) of the unexpected deaths and 2/53 (4%) of the unexpected survivors. Some 10/53 (19%) of the unexpected survivors died within a few months of the 7-day period of model prediction. We found little evidence that deaths occurring in patients with a low predicted mortality from risk-adjustment could be attributed to the quality of healthcare provided.


Endothelial progenitor cells transfected with PDGF: cellular and molecular targets for prevention of diabetic microangiopathy.
Microvascular insufficiency represents a major cause of end-organ failure among diabetics. Prevention at early stage of disease is therefore necessary and is a focus of current investigations. Progression of diabetes is complicated by endothelial cell apoptosis as well as occlusion of arteriole and capillary leading to microvascular rarefaction. This favors the formation of non-healing limb ulcers and limits the benefit of revascularization. Recent study indicated that reduction of platelet derived growth factor (PDGF) expression was indeed critical, in causing functional and morphological vascular changes, namely the dissociation of pericytes from the capillaries in muscles. Diabetic microangiopathy is a result of pericytes dissociation from reduced PDGF as well as vessel rarefaction from reduced number of endothelial progenitor cells (EPCs) and EPC dysfunction. Since blood vessels develop through the assembly of these two principal cell types--endothelial cells and pericytes/smooth muscle cells, prevention of diabetic microangiopathy requires interventions targeting at both cell types in a complementary and synergistic manner. An improved recruitment of EPCs will help repair of injured endothelium while molecular targeting with PDGF will enhance pericytes recruitment. EPCs modified with PDGF therefore hold promise as the next generation of agents for prevention of microangiopathy.


Nerve membrane Na+ channels as targets of insecticides.
The mechanisms of action of neuroactive insecticides on the nervous system has been studied for many years. It is now well established that severe neurological symptoms of poisoning with pyrethroids and DDT in mammals and insects are the result of modification of Na+ channel activity. Toshio Narahashi discusses the history, approaches and results of the studies leading to this conclusion. Advanced electrophysiological experiments using voltage clamp and patch clamp, together with ligand-binding and ionic flux experiments, have unveiled unique actions of pyrethroids and DDT of keeping the Na+ channel in the open state for an extremely long period, sometimes as long as several seconds. This modification of Na+ channel properties leads to hyperactivity of the nervous system. These insecticides have also been shown to suppress GABA and glutamate receptor-channel complexes and voltage-activated Ca2+ channels, but the toxicological significance of these actions remains to be seen. The results of these studies provide clues for developing newer insecticides with higher selectivity between mammals and insects and for coping with the problem of insecticide resistance.


Systematic review of recent advances in pharmacokinetics of four classical Chinese medicines used for the treatment of cerebrovascular disease.
Recent studies have focused more on Chinese medicine used for the treatment of cerebrovascular disease. The current review covers researches on the pharmacokinetics of Chinese medicine, providing a convenient reference for researchers to increase efficiency of drug discovery, by compiling and discussing the pharmacokinetics of four classical Chinese medicines for therapy of cerebrovascular disease containing: Panax notoginseng, Salvia miltiorrhiza, Ligusticum Chuanxiong and Gardenia. It also helps to eliminate side effect as far as possible from inappropriate Chinese medicine usage. Current integrative and comprehensive review of Chinese medicine for cerebrovascular disease including 1) the absorption of some constituents is limited such as ginsenosides Rg1 and Rb1. It may be affected by gastric juice, first-pass effect, etc. 2) The interactions between Chinese medicine and prescription can occur. Borneol and carbomer would enhance the absorption of R1 and Rg1 in vivo by increasing adjacent cell transport ability. 3) The distribution of active constituents in brain is important for cerebrovascular disease. BBB protects brain from xenobiotic. Intranasal, intra-tympanic administration is a promising alternative to conventional administration to reach brain for ligustrazine. 4) Renal excretion is the uppermost route of these Chinese medicines. But biliary, fecal and urinary excretion are the other major routes. Theoretical and practical aspects are described with pharmacokinetic examples. In the end, this paper also discusses recent development of bio-analysis of Chinese medicine.


Combined genetic variants of human cytomegalovirus envelope glycoproteins as congenital infection markers.
Human cytomegalovirus (HCMV) is still considered to be the main viral cause of birth defects and long-term neurological and sensory sequelae following congenital infection. Several Authors sustain a key role of HCMV envelope glycoproteins, such as gB, gN and gO - mainly involved in cell targeting, viral penetration and spread - as putative virulence factors. The genes coding for these glycoproteins possess hypervariable regions, resulting in a number of genetic variants in circulating clinical strains. Considering that the genetic polymorphisms underlying the specific differences between gB, gN and gO genotypes can influence the ability of HCMV to preferentially target specific host cells, it is very likely that they play an important role in defining HCMV infection outcome. In the present study, we analysed HCMV gB, gN and gO gene polymorphisms in viral strains isolated from paediatric patients with congenital or post-natal infection, to investigate whether specific genetic variants may be associated with congenital infection. The restriction fragment polymorphisms of genes coding for HCMV gB (UL55), gN (UL73) and gO (UL74) were investigated by analysing viral DNA extracted from 40 urine samples of as many paediatric patients with congenital or post-natal HCMV infection. Randomly selected samples were subjected to DNA sequencing and phylogenetic analysis. Statistical analysis was performed using Fisher's exact test to assess the significance of single and combined glycoprotein genotypes frequency distribution. Statistical significance was considered at a P <0.05. While gB genomic variants were quite homogeneously represented in both paediatric groups, the gN4 genotype significantly prevailed in congenitally infected children (89.5 %) vs post-natally infected children (47.6 %), with a predominance of the gN4c variant (47.4 %). A similar trend was observed for gO3 (52.6 % vs 19 %). Concerning genotypes association, a statistically significant (P = 0.037) gN4-gO3 combination was found specifically in the congenitally infected group. The results indicate that the gN4 (mostly the gN4c variant) and gO3 combined genotypes could provide useful markers of congenital infection and represent suitable candidate molecules for prophylactic vaccine preparations.


Thrombin generation assay as a biomarker of cardiovascular outcomes and mortality: A narrative review.
Cardiovascular diseases (CVDs) are currently the leading cause of death worldwide. Therefore, there is interest in the search for cardiovascular risk markers that contribute to the early diagnosis, monitoring and prevention of cardiovascular events. Considering that CVDs present in their pathophysiology a strong interaction between inflammation and hemostasis, thrombin, a key enzyme in the clotting process can be thought as a possible biomarker of cardiovascular risk. The thrombin generation assay (TGA) by the Calibrated Automated Thrombogram (CAT) method has been used in numerous prospective studies. It is a relatively recent laboratory tool capable of globally evaluating the functioning of the hemostatic system through the determination of thrombin generation for investigating the contribution of procoagulants and natural anticoagulants, in addition to the effect of different drugs and a range of factors that interfere in this system. The analysis of thrombin generation can be a promising tool for estimating the risk of thrombotic diseases, although the association of TGA with arterial thrombosis has only recently attracted interest and remains to be better understood. The association between thrombin generation and cardiovascular events, especially acute myocardial infarction (AMI) and stroke, all-cause and cardiovascular mortality is still poorly investigated and the results are often inconsistent. Assessing the relationship between TGA and CVDs may not only contribute to increasing knowledge of the pathophysiological process that leads to coronary and cerebrovascular diseases, but may also suggest a new approach to prevention. In this article we review and summarize the results of the main studies that evaluated whether TGA parameters were associated with cardiovascular events, cardiovascular mortality and all-cause mortality. Possible contributing factors to the observed inconsistencies were also speculated.


Modulation of mesenchymal stem cell actin organization on conventional microcarriers for proliferation and differentiation in stirred bioreactors.
Tissue engineering applications require an appropriate combination of a cell population, biochemical factors and scaffold materials. In this field, mesenchymal stem cells (MSCs) emerge as an attractive cell population, due to their ready availability and their potential to be differentiated into various mesodermal cell types. Commercially available microcarriers have been recently recognized as an efficient tool for the propagation of such cells compared to traditional monolayer culture, enabling efficient scale-up and serving as a cell delivery system. The organization of actin as well as the induction of its effectors was previously shown to affect dramatically both proliferation and differentiation of MSCs in monolayer culture. To achieve mass scale production of differentiated cells derived from MSCs in scalable stirred bioreactors, this work aims at rationally screening microcarriers based on the characterization of actin organization. First, among the various supports tested, gelatin-based microcarriers were found to be most suitable for MSC expansion, due to their best-adapted actin organization compared to monolayer cultures. Secondly, the proper actin organization on Cultispher-S was closely linked to its ability to bind serum adhesion molecules enabling Rho GTPase activation. Finally, by modulating actin behaviour, it was feasible to efficiently guide MSC differentiation on microcarriers. Taken together, these results show that controlling actin behaviour is a good strategy toward mass scale sequential expansion followed by differentiation of MSCs in a microcarrier based bioreactor.


Pigmentary abnormalities of the nails with emphasis on systemic diseases.
The nails can change colors for many reasons. White bands called leukonychia are especially common. The shape of the white band, that is, concave or convex, indicates the site of injury. Color changes in the nails may also be a sign of a variety of cutaneous or systemic disorders.


Dendritic cell paucity in mismatch repair-proficient colorectal cancer liver metastases limits immune checkpoint blockade efficacy.
Liver metastasis is a major cause of mortality for patients with colorectal cancer (CRC). Mismatch repair-proficient (pMMR) CRCs make up about 95% of metastatic CRCs, and are unresponsive to immune checkpoint blockade (ICB) therapy. Here we show that mouse models of orthotopic pMMR CRC liver metastasis accurately recapitulate the inefficacy of ICB therapy in patients, whereas the same pMMR CRC tumors are sensitive to ICB therapy when grown subcutaneously. To reveal local, nonmalignant components that determine CRC sensitivity to treatment, we compared the microenvironments of pMMR CRC cells grown as liver metastases and subcutaneous tumors. We found a paucity of both activated T cells and dendritic cells in ICB-treated orthotopic liver metastases, when compared with their subcutaneous tumor counterparts. Furthermore, treatment with Feline McDonough sarcoma (FMS)-like tyrosine kinase 3 ligand (Flt3L) plus ICB therapy increased dendritic cell infiltration into pMMR CRC liver metastases and improved mouse survival. Lastly, we show that human CRC liver metastases and microsatellite stable (MSS) primary CRC have a similar paucity of T cells and dendritic cells. These studies indicate that orthotopic tumor models, but not subcutaneous models, should be used to guide human clinical trials. Our findings also posit dendritic cells as antitumor components that can increase the efficacy of immunotherapies against pMMR CRC.


More than just blood, saliva, or sperm-setup of a workflow for body fluid identification by DNA methylation analysis.
The determination of cellular origin of DNA is a useful method in forensic genetics and complements identification of the DNA donor by STR analysis, since it could provide helpful information for the reconstruction of crime scenes and verify or disprove the descriptions of involved people. There already exist several rapid/pre-tests for several secretions (blood, sperm secretion, saliva, and urine), RNA-based expression analyses (blood, menstrual blood, saliva, vaginal secretion, nasal secretion, and sperm secretion), or specific CpG methylation analyses (nasal blood, blood, saliva, vaginal secretion, nasal secretion, and sperm secretion) for determining the cell type.To identify and to discriminate seven different body fluids and mixtures thereof in a simple workflow from each other, assays based on specific methylation patterns at several CpGs combined with pre-/rapid tests were set up in this study. For each of the seven secretions listed above, we selected the CpG marker achieving the highest possible discrimination (out of 30 markers tested). Validation studies confirmed a definite identification for saliva, vaginal secretion, and semen secretion in 100% of samples as well as discrimination from all other secretions. Moreover, the unambiguously correctly determined proportion of nasal samples, blood and menstrual blood varied between 61% (nasal blood) and 85% (nasal secretion).In summary, our workflow proved to be an easy and useful tool in forensic analysis for the identification and discrimination of seven different body fluids often found at a crime scene.


Liver Transplantation: Analysis of Preservation Solutions in the Andalusian Registry.
The initial objective of this study is to analyze the impact on survival of the preservation solution used. Secondarily, the influence of donor age, underlying pathology, and graft ischemia time is investigated. A multicenter retrospective analytical observational study has been carried out. A population of 1822 liver transplant recipients is studied in 4 Andalusian hospitals between 1995 and 2014. Survival of the patient and graft is analyzed by groups based on the conservation solution used, the age of the donor, the pathology indicated for transplant and the ischemia time, and the relationship between the variables through a bivariate study. A descriptive and predictive multivariate analysis of the variables was performed. Comparison of the graft and patient survival functions for each preservation solution did not differ significantly. The bivariate analysis shows a significantly higher utilization of Celsior and histidine-tryptophan-ketoglutarate solution in graft loss. The comparison between donor age groups showed significant differences in favor of donor grafts younger than 50 years. In the multivariate analysis of patient and graft survival, the donor age obtained a hazard ratio of 1.008 (P < .005) with donors older than 47.6 and 47.5 years, respectively. Survival analysis between pathology groups found significant differences, not obtaining predictive power for patient or graft survival in the multivariate study. No significant differences were found in survival according to ischemia time, but there was a relationship between early graft loss and longer mean cold ischemia times up to 18 hours.


Relation of blood pressure during exercise to anaerobic metabolism.
To determine the effects of anaerobic metabolism on blood pressure (BP), 25 subjects were studied for BP response to graded and continuous leg-crank ergometry under both aerobic and anaerobic conditions. Measurements obtained during exercise also included ventilatory equivalents for oxygen and carbon dioxide to determine anaerobic threshold. Systolic and diastolic BP responses to exercise before anaerobic threshold were compared with responses after anaerobic threshold by linear regression analyses. The systolic BP response to graded exercise was significantly accelerated (p less than 0.01) after anaerobic threshold, demonstrating a nonlinear response to proportionately graded exercise demand. Comparison of the slopes or rates of change in diastolic BP before and after anaerobic threshold also indicated a significant difference (p less than 0.01) under these 2 different metabolic conditions. It is concluded that in contrast to the linear response of BP under conditions of aerobic metabolism, BP responds nonlinearly during anaerobic metabolism.


Is there a role for oral antihyperglycemics in gestational diabetes and type 2 diabetes during pregnancy?
Diabetes mellitus is a heterogeneous disorder of glucose intolerance that is generally classified into the following categories: type 1 and type 2 diabetes and gestational diabetes (GDM). Currently, the number of pregnancies complicated by type 2 diabetes and GDM exceed those affected by type 1 diabetes. Numerous studies have established a direct relationship between maternal glycemic control and neonatal outcomes for all types of diabetes. Therefore, modern treatment protocols during pregnancy emphasize strict glycemic control by a combination of diet and medication. Traditionally, insulin therapy has been considered the gold standard for management because of its efficacy in achieving tight glucose control and the fact that it does not cross the placenta. Since GDM and type 2 diabetes are characterized by insulin resistance and relatively decreased insulin secretion, treatment with oral antihyperglycemic agents that target these defects is of potential interest. However, because of concerns regarding transplacental passage and, therefore, the possibility of fetal teratogenesis and prolonged neonatal hypoglycemia, these agents are not currently recommended in pregnancy. There are no randomized controlled trials on which to draw conclusions regarding the teratogenicity of these oral agents. However, most retrospective studies and the published clinical experience have not demonstrated an increased risk of malformed infants among women treated with oral antihyperglycemic agents. Rather, the data indicate that the increased risk for major congenital anomalies appears to be related to maternal glycemic control prior to and during conception. These studies and currently available data on the use of both metformin and sulfonylureas in pregnancy have also failed to demonstrate an increased risk of neonatal hypoglycemia and other neonatal morbidities. To date, there has only been one randomized controlled trial to test the effectiveness and safety of sulfonylurea therapy (glyburide [glibenclamide]) in the management of women with GDM. Both the insulin- and glyburide-treated women were able to achieve satisfactory glucose control and had similar perinatal outcomes. Glyburide was not detected in the cord serum of any infant in the glyburide group. In summary, based on the currently available data, it appears that glyburide could be safely and effectively utilized in the management of GDM. However, more intensive investigation regarding the safety and feasibility of oral agents in pregnancies complicated by type 2 diabetes is necessary. It is important to emphasize that it is the level of metabolic control achieved and not the mode of therapy that is crucial to improving outcomes in these pregnancies.


Diet and sexual dimorphism in the very catholic lizard genus, Leiocephalus of the Bahamas.
Over 5,000 prey items from specimens of Bahamian Leiocephalus lizards were measured and identified taxonomically. The diet in general consists mainly of arthropods, but much plant matter is also eaten, including flowers and buds as well as fruit. Lizards comprise about 2% of the diet by volume. Individuals inhabiting relatively small islands are more likely to have eaten plant matter than those from relatively large islands. Within the most widespread species (carinatus), sexual dimorphism in size is greater, the smaller the number of sympatric species in its structural habitat. Prey-size differences between differently sized Leiocephalus are greater, the greater the dimorphism. However, even the most dimorphic sexes take rather similar prey sizes. For all Bahamian species combined, the inverse correlation of sexual dimorphism with sympatric species is not as strong as an inverse correlation with latitude. We suggest that sexual selection on female size to increase the clutch size that can be carried may have affected sexual dimorphism in the genus.


Modelling the spatial distribution of the nuisance mosquito species Anopheles plumbeus (Diptera: Culicidae) in the Netherlands.
Landscape modifications, urbanization or changes of use of rural-agricultural areas can create more favourable conditions for certain mosquito species and therefore indirectly cause nuisance problems for humans. This could potentially result in mosquito-borne disease outbreaks when the nuisance is caused by mosquito species that can transmit pathogens. Anopheles plumbeus is a nuisance mosquito species and a potential malaria vector. It is one of the most frequently observed species in the Netherlands. Information on the distribution of this species is essential for risk assessments. The purpose of the study was to investigate the potential spatial distribution of An. plumbeus in the Netherlands. Random forest models were used to link the occurrence and the abundance of An. plumbeus with environmental features and to produce distribution maps in the Netherlands. Mosquito data were collected using a cross-sectional study design in the Netherlands, from April to October 2010-2013. The environmental data were obtained from satellite imagery and weather stations. Statistical measures (accuracy for the occurrence model and mean squared error for the abundance model) were used to evaluate the models performance. The models were externally validated. The maps show that forested areas (centre of the Netherlands) and the east of the country were predicted as suitable for An. plumbeus. In particular high suitability and high abundance was predicted in the south-eastern provinces Limburg and North Brabant. Elevation, precipitation, day and night temperature and vegetation indices were important predictors for calculating the probability of occurrence for An. plumbeus. The probability of occurrence, vegetation indices and precipitation were important for predicting its abundance. The AUC value was 0.73 and the error in the validation was 0.29; the mean squared error value was 0.12. The areas identified by the model as suitable and with high abundance of An. plumbeus, are consistent with the areas from which nuisance was reported. Our results can be helpful in the assessment of vector-borne disease risk.


Does Community College Attendance Affect Matriculation to a Physician Assistant Program? A Pathway to Increase Diversity in the Health Professions.
To explore whether community college (CC) applicants were a significant contributor to the diversity of matriculants to physician assistant (PA) programs and whether CC applicants were less likely to matriculate to PA programs than non-CC applicants. The authors used national data from the 2016-2017 application cycle. They categorized applicants to PA programs into 5 pathways: HS-CC (applicant attended CC while in high school), first-CC (applicant attended CC before a 4-year university), 4Y-CC (applicant attended CC while at a 4-year university), post-CC (applicant attended CC after graduating from a 4-year university), and no-CC (applicant never attended CC). The authors used Pearson chi-square and Kruskal-Wallis H tests and the appropriate post hoc tests to assess whether applicants in the 4 CC pathways were more diverse in terms of their race, ethnicity, gender, rurality, and socioeconomic status than those in the no-CC pathway. They used logistic regressions to assess associations between the CC pathways and matriculation to a PA program. Among the 8,577 matriculants in the 2016-2017 application cycle, more than 75% attended a CC at some point. First-CC and post-CC matriculants were more likely to be Black (P < .001) or Hispanic (P < .001) and come from a disadvantaged background (P < .001) than no-CC matriculants. After adjusting for applicant demographics, academic performance, rurality and socioeconomic status, and application strategy, first-CC applicants had 17% lower odds of matriculating to a PA program than no-CC applicants (P < .001). CCs are an important pathway to the PA profession, with 3 of 4 matriculants having a CC background. However, lower matriculation rates among similarly qualified applicants who transferred from a CC to a 4-year university than among applicants with no-CC background suggest that PA programs are missing important opportunities for increasing student diversity and thereby the profession.


Ex Vivo Imaging, Biodistribution, and Histological Study in Addition to In Vivo Imaging.
In addition to in vivo fluorescence imaging, ex vivo evaluations including ex vivo imaging, biodistribution, and histological study are often conducted to further investigate the biological behavior of fluorescent probes. These studies can further confirm the localization of fluorescent probes at the target sites and demonstrate the probe distribution in various organs and tissues. Such studies can also be extended to cellular level for biochemical analysis. Therefore, ex vivo evaluations are valuable to fully characterizing fluorescent probes in a living system. This chapter provides an overview of techniques for evaluating pharmacological profiles of fluorescent probes ex vivo.


The influence of attitudes, acculturation, and gender on substance use for Mexican American middle school students.
The present study tested if current drug use was related to acculturation (measured by language spoken at home), gender, or youth attitudes towards drugs in a large sample of 8th grade, predominantly Mexican American, Hispanic youth. The data were obtained via self-report survey from 2964 Hispanic youth in 108 schools. Hierarchical linear modeling (HLM) was used to test if acculturation, gender, or youth attitudes towards drugs predicted past 30-day use of alcohol, inhalant, or marijuana use and assess school-level influences. Acculturation and gender interacted with attitudes towards drugs to predict current alcohol use. Gender interacted with attitudes towards drugs to predict current alcohol and inhalant use. Having positive attitudes towards drugs was related to increased substance use for all three drug types. Hispanic eighth grade girls had significantly higher use rates than boys for both alcohol and inhalants. Additional research is needed to better understand the influence of acculturation on substance use among Hispanic youth.


Bone remodelling in the mouse tibia is spatio-temporally modulated by oestrogen deficiency and external mechanical loading: A combined in vivo/in silico study.
Osteoporosis disrupts the healthy remodelling process in bone and affects its mechanical properties. Mechanical loading has been shown to be effective in stimulating bone formation to mitigate initial bone loss. However, no study has investigated the effects of repeated mechanical loading, with a pause of one week in between, in the mouse tibia with oestrogen deficiency. This study uses a combined experimental and computational approach, through longitudinal monitoring with micro-computed tomography, to evaluate the effects of loading on bone adaptation in the tibiae of ovariectomised (OVX) C57BL/6 mice from 14 to 22 weeks of age. Micro-FE models coupled with bone adaptation algorithms were used to estimate changes in local tissue strains due to OVX and mechanical loading, and to quantify the relationship between local strain and remodelling. The first in vivo mechanical loading increased apposition, by 50-150%, while resorption decreased by 50-60%. Both endosteal and periosteal resorption increased despite the second mechanical loading, and periosteal resorption was up to 70% higher than that after the first loading. This was found to correlate with an initial decrease in average strain energy density after the first loading, which was lower and more localised after the second loading. Predictions of bone adaptation showed that between 50 and 90% of the load-induced bone apposition is linearly strain driven at the organ-level, but resorption is more biologically driven at the local level. The results imply that a systematic increase in peak load or loading rate may be required to achieve a similar bone adaptation rate in specific regions of interests.


A phase II trial of diaziquone in patients with head and neck cancer.
Diaziquone (AZQ) is a lipophilic alkylating agent which crosses the blood-brain barrier and has marked antitumor activity in a broad spectrum of murine tumor systems. Myelosuppression has been the dose-limiting toxicity in phase I trials. In this study 36 patients with head and neck cancer received diaziquone. Thirty-one of these patients (28 male, 3 female) were evaluable for efficacy. The initial starting dose was 7 mg/m2/day X 5 days i.v. repeated every 28 days. Because of the severe myelosuppression encountered in the first four patients, the starting dose was decreased by 20% to 5.5 mg/m2/day X 5 days repeated every 28 days. The majority of patients were considered to be good-risk patients as evidenced by performance status (80% 0-1 Zubrod) and prior therapy. Even with this dosage reduction, myelosuppression (especially thrombocytopenia) was again the dose-limiting toxicity with 25% of patients experiencing granulocyte and platelet nadirs below 1000/mm3 and 50,000/mm3 respectively. Thirty-five percent of patients required a subsequent dosage reduction of 20% prior to receiving a second course of therapy. There was one complete (CR), four partial (PR) and three minor (MR) responses. All but the CR were of relatively short duration (mean of 30 days). The patient with a CR has remained disease-free for nearly 3 years. In this group of patients the activity of diaziquone as a single agent at this dose and schedule (CR + PR + MR = 26%; CR + PR = 16%) is less than that of methotrexate, bleomycin, and cis-platinum but is encouraging. Further trials utilizing combinations are warranted.


Optical property of iron binding to Suwannee River fulvic acid.
In this work, absorbance and fluorescence spectra were used to study iron binding to standard Suwannee River fulvic acid (SRFA). The differential logarithm-transformed absorbance and fluorescence spectra of SRFA induced by iron binding were processed to examine the nature of the observed phenomena and to investigate the contributions of discrete binding sites present in SRFA. Both the Fe-differential log-transformed absorbance and fluorescence were well correlated to the bound iron concentrations predicted based on the Non-ideal Competitive Adsorption (NICA-Donnan) model at iron concentrations below 10.0μM (R(2)>0.99 for absorbance and R(2)>0.97 for fluorescence) and over a wide pH range of 3.5-8.0. At pH3.5, both the Fe-differential log-transformed absorbance and fluorescence vs. iron bound spectra exhibited significantly lower slopes than those at pH5.0, 7.0, and 8.0. These results suggest that a different set of complexation-active chromophores and fluorophores are responsible for iron binding at low pH values or that the NICA-Donnan model is limited at low pH. Because phenolic and carboxylic complex sites of different fluorophores respond to iron quenching, the fluorescence data indicate three stages of iron binding to phenolic, carboxylic, and Donnan gels (electrostatic interactions) in SRFA (with R(2)>0.99 at each stage). The agreement between observations from spectroscopic indices and established metal-binding models shows that the absorbance and fluorescence spectra provide important information about the involvement of metal complexation of specific functional groups typical for fulvic acids.


The impact of skin viability on drug metabolism and permeation -- BSA toxicity on primary keratinocytes.
For testing cutaneous absorption of drugs, ingredients of cosmetics and also for risk assessment of industrial compounds predictable in vitro test protocols are under investigation using excised skin or reconstructed human epidermis. Since the metabolizing enzymes expressed by viable skin can influence the absorption behaviour of substances by changing their structure and thereby their physicochemical characteristics, the metabolic capacity should be considered in the design of the test protocols of compounds susceptible to metabolism. Then data, generated using viable reconstructed epidermis may reflect the in vivo situation. Interestingly, bovine serum albumin (BSA) commonly used in receptor media in permeation studies to facilitate solubility of highly lipophilic substances strongly inhibited the metabolism of topically applied prednicarbate in reconstructed epidermis. Here, we show that 5% BSA is toxic to reconstructed epidermis and keratinocytes which was consistent with the earlier findings. While media toxicity (deficiency media) was at least partly the cause of both apoptotic and necrotic processes in keratinocytes, BSA only slightly increased the rate of necrotic cells. Moreover, caspase inhibitors did not reduce BSA toxicity. Yet, the results show that BSA toxicity on keratinocytes has to be carefully considered if this protein is used in permeation studies with reconstructed epidermis.


TMI? not in today's health care world.
Everybody wants health care providers to better engage patients and their families. But wanting it to happen and making it happen are two different things.


Protein antioxidants in thalassemia.
It is common knowledge that thalassemic patients are under significant oxidative stress. Chronic hemolysis, frequent blood transfusion, and increased intestinal absorption of iron are the main factors that result in iron overload with its subsequent pathophysiologic complications. Iron overload frequently associates with the generation of redox-reactive labile iron, which in turn promotes the production of other reactive oxygen species (ROS). If not neutralized, uncontrolled production of ROS often leads to damage of various intra- and extracellular components such as DNA, proteins, lipids, and small antioxidant molecules among others. A number of endogenous and exogenous defense mechanisms can neutralize and counteract the damaging effects of labile iron and the reactive substances associated with it. Endogenous antioxidant enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, and ferroxidase, may directly or sequentially terminate the activities of ROS. Nonenzymatic endogenous defense mechanisms include metal binding proteins (ceruloplasmin, haptoglobin, albumin, and others) and endogenously produced free radical scavengers (glutathione (GSH), ubiquinols, and uric acid). Exogenous agents that are known to function as antioxidants (vitamins C and E, selenium, and zinc) are mostly diet-derived. In this review, we explore recent findings related to various antioxidative mechanisms operative in thalassemic patients with special emphasis on protein antioxidants.


Faciolingual Hemiparesis with Mild Limb Weakness of Cortical Origin.
The clinical combination of unilateral facial and hypoglossal palsy with upper limb weakness is known as the capsular genu syndrome and responds most often to an ischemic infarct in the internal capsule. We here describe a patient with this peculiar combination, in whom the responsible lesion was located in the contralateral prefrontal cortex, involving the corresponding areas of the Penfield's homunculus. Contralateral cortical frontal lesions should be considered in patients with facial and hypoglossal palsy with upper limb weakness.


Trinuclear heterobimetallic Ni2Ln complexes [L2Ni2Ln][ClO4] (Ln=La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, and Er; LH3=(S)P[N(Me)NCH-C6H3-2-OH-3-OMe]3): from simple paramagnetic complexes to single-molecule magnet behavior.
The reaction of LH3 with Ni(ClO4)(2).6H 2O and lanthanide salts in a 2:2:1 ratio in the presence of triethylamine leads to the formation of the trinuclear complexes [L2Ni2Ln][ClO4] (Ln=La (2), Ce (3), Pr (4), Nd (5), Sm (6), Eu (7), Gd (8), Tb (9), Dy (10), Ho (11) and Er (12) and L: (S)P[N(Me)NCH-C6H3-2-O-3-OMe]3). The cationic portion of these complexes consists of three metal ions that are arranged in a linear manner. The two terminal nickel(II) ions are coordinated by imino and phenolate oxygen atoms (3N, 3O), whereas the central lanthanide ion is bound to the phenolate and methoxy oxygen atoms (12O). The Ni-Ni separations in these complexes range from 6.84 to 6.48 A. The Ni-Ni, Ni-Ln and Ln-O phenolate bond distances in 2-12 show a gradual reduction proceeding from 2 to 12 in accordance with lanthanide contraction. Whereas all of the compounds (2-12) are paramagnetic systems, 8 displays a remarkable ST=(11)/2 ground state induced by an intramolecular Ni. . .Gd ferromagnetic interaction, and 10 is a new mixed metal 3d/4f single-molecule magnet generated by the high-spin ground state of the complex and the magnetic anisotropy brought by the dysprosium(III) metal ion.


Spinal muscular atrophy in childhood: review of 50 cases.
The clinical findings in 50 children with intermediate or mild spinal muscular atrophy are reviewed. An early age of onset and the presence of tongue fasciculation carry a poor prognosis for disability. Scoliosis appears early in nearly all children with the more severe forms of spinal muscular atrophy and early energetic treatment is indicated. Contractures are also found in both the more severe and the milder forms and are the main cause of progressive disability, since continuous deterioration of muscle power was not evident in the present series. Respiratory failure is rare but potentially fatal, and may occur even in mild forms of the disease. Clinically evident weakness of the axial musculature may give warning of this complication.


Anion fluxes in three Indiana forests.
The major ions in soil solution in control and disturbed plots were measured over a year in three Indiana forests. The major ions in bulk precipitation were hydrogen and sulfate. Sulfate, calcium, and magnesium were the most important ions in the soil solution in control plots, while in disturbed plots nitrate, calcium, and magnesium were most important. Increase nitrate production and loss following disturbance caused a large increase in cation losses.


Heterobinuclear copper(II)‑platinum(II) complexes with oxindolimine ligands: Interactions with DNA, and inhibition of kinase and alkaline phosphatase proteins.
Two mononuclear copper(II) compounds, [Cu(isad)(H2O)Cl]Cl 1 and [Cu(isah)(H2O)Cl]Cl 2, and its corresponding heterobinuclear species containing also platinum(II), [CuCl(isad)Pt(NH3)Cl2] 3 and [CuCl(isah)Pt(NH3)Cl2] 4 (where isad and isah are oxindolimine ligands, (E)-3-(2-(3-aminopropylamino)ethylimino)indolin-2-one, and (E)-3-(3-amino-2-hydroxypropylimino)indolin-2-one, respectively), have been previously synthesized and characterized by different spectroscopic techniques in our laboratory. Cytotoxicity assays performed with B16F10 murine cancer cells, and MES-SA human uterine sarcoma cells, showed IC50 values lower or in the same order of cisplatin. Herein, in order to better elucidate their probable modes of action, possible interaction and damage to DNA, as well as their effect on the activity of crucial proteins were verified. Both mononuclear complexes and the binuclear compound 4 displayed a significant cleavage activity toward plasmid DNA, while compound 3 tends to protect DNA from oxidative damage, avoiding degradation. Complementary experiments indicated a significant inhibition activity toward cyclin-dependent kinase (CDK1/cyclinB) activity in the phosphorylation of histone H1, and only moderate inhibition concerning alkaline phosphatase. Results also revealed that the reactivity is reliant on the ligand structure and on the nature of the metal present, in a synergistic effect. Simulation studies complemented and supported our results, indicating different bindings of the binuclear compounds to DNA. Therefore, the verified cytotoxicity of these complexes comprises multiple modes of action, including modification of DNA conformation, scission of DNA strands by reactive oxygen species, and inhibition of selected proteins that are crucial to the cellular cycle.


Neonatal outcome of macrosomic infants: an analysis of a two-year period.
To assess the neonatal outcome of macrosomic neonates in uncomplicated, singleton, term deliveries. A retrospective analysis was performed on 5738 live-born term neonates born in the period 2008-2009. The neonatal outcomes were compared between two birth weight (BW) groups: the macrosomic neonates born with BW≥4000g and a control group: 2500-3999g. There were 410 (7.1%) neonates in the macrosomic group, 4757 (82.9%) in the control group, while 571 (10.0%) were less than 2500g at birth. A correlation analysis of two subgroups of the macrosomic neonates (4000-4499g vs. ≥4500g) was also carried out. The rate of caesarean section (CS) was significantly higher in the macrosomic group as compared with the control group (49.3% vs. 39.9%), as were the prevalences of hypoglycaemia (6.1% vs. 2.9%), adrenal haemorrhage (0.98% vs. 0.15%) and the male to female ratio (2.15 vs. 0.95). The rate of icterus was significantly higher in the control group (30.4% vs. 18.5%). The macrosomic subgroups were similar in many aspects, but we found significantly more neonates in the higher weight subgroup as regards a low Apgar score, clavicle fracture and the need for intensive care. The macrosomic infants were born in good general condition, although those with BW ≥4500g more frequently had an adverse outcome. The macrosomic and control groups' data revealed significant differences in the rate of CS, the male to female ratio, hypoglycaemia and adrenal haemorrhage.


Targeted radionuclide therapy for bone metastases.
Recent advances in targeted radiotherapy offer a new approach for the management of metastatic bone pain. This paper will review the scientific basis for radionuclide therapy and will examine the evidence for clinical efficacy. The therapeutic potential of targeted radiotherapy can only be appreciated by comparison with established treatments. Alternative treatment options will, therefore, be discussed, to bring the potential advantages and hazards of targeted radiotherapy into perspective and to define its place in routine management.


Tuning the lattice parameters and porosity of 2D imine covalent organic frameworks by chemically integrating 4-aminobenzaldehyde as a bifunctional linker.
As the available building blocks are limited, improving the structural complexity of covalent organic frameworks (COFs) is still challenging. In this work, a new three-component COF synthesis strategy is established by using 4-aminobenzaldehyde as the bifunctional linker. The lattice parameters, crystallinity, and porosity of these COFs can be efficiently tuned by varying the amount of this linker. This work provides a new way to expand the structural diversity and complexity of imine-linked COFs.


The effects of gastrin and gastrin analogues on pancreatic acinar cell membrane potential and resistance.
1 Intracellular recordings of membrane potentials and input resistance have been made from the exocrine acinar cells of mouse and rat pancreas placed in a tissue bath perfused with Krebs-Henseleit solution.2 The resting acinar cell membrane potential was about -38 mV. The acinar cells were stimulated by cholecystokinin-pancreozymin (CCK-PZ), gastrin and the gastrin-related polypeptides, caerulein and desulphated caerulein. The immediate effect of stimulation with these secretagogues was always a depolarization and a concomitant reduction in input resistance and time constant. Depolarization of the acinar cell membrane by these secretagogues was not abolished in the presence of atropine (1.4 muM).3 These peptide secretagogues were divided into the gastrin group and the CCK-PZ group according to the time course of the depolarizations and the shape of the dose-response curve. The depolarization evoked by the gastrin group returned quickly to the resting level but that evoked by the CCK-PZ group was long lasting. The time course and the dose-response curve for desulphated caerulein was identical with that of gastrin.4 It was confirmed electrophysiologically that the activity of gastrin is exerted by the C-terminal tetrapeptide; but the activity of caerulein depends on the C-terminal heptapeptide, especially the presence in the molecule of the sulphated tyrosyl residue at position 7 (numbering from the C-terminus). The equivalent sulphated tyrosyl residue in CCK-PZ is probably necessary for optimal activity of this polypeptide.5 The dose-response curves obtained by electrophysiological methods indicated that the relative potencies of the peptides on mouse pancreatic acinar cells were caerulein > CCK-PZ > gastrin. Synthetic human gastrin I was found to have a higher potency than either tetra- or pentagastrin.


Trick or Drink: Offline and Social Media Hierarchical Normative Influences on Halloween Celebration Drinking.
The current study examined the relationship between perceived societal and personal celebration drinking norms, social media use, and alcohol consumption during Halloween. The study used a survey of a nationally representative, convenience, and cross-sectional sample of underage youth (18-20 years old; N = 525). Participants self-reported their own drinking, perceived descriptive norms among peers and close friends, and alcohol-related social media posting and interaction during Halloween. Results revealed that underage youth's estimation of societal drinking norms related to their proximal close friends' drinking norms, which in turn, influenced self-reported number of drinks consumed during Halloween. Social media posting and interaction with alcohol-related content were associated with greater descriptive normative perceptions and self-reported drinking. Extending the hierarchical social norms approach, our findings showed that normative perceptions about proximal reference groups' drinking, along with alcohol-related social media activities, were associated with greater number of drinks consumed during Halloween.


Role of an external electric field on hybrid halide perovskite CH3NH3PbI3 band gaps.
The organic-inorganic perovskite CH3NH3PbI3 has attracted much attention due to their power conversion efficiency as a potential photovoltaic material, but the role of an external electric field has not been well understood. Based on first-principles calculations, the effects of an external electric field (E) applied along the [111] direction of the orthorhombic perovskite, CH3NH3PbI3, on its electronic structure and optical properties are investigated. Our results indicate that the electric field strength affects the band gap (Eg) of CH3NH3PbI3 (MAPbI3, MA = CH3NH3). The energy difference between the two peaks closest to the Fermi level in the density of states diagram decreases with increasing applied electric field strength along the [111] direction, indicating that the covalent character increases between A-sites cations and I-sites anions. Both the cell volume and the final energy show the same increasing trend. The absorption peaks move toward the visible-frequency range, with the optimal band gap of 1.1-1.45 eV and E = 0.04-0.06 eV/Å/e. In particular, the non-linear change of the second-order Stark effect causes a non-linear change in the band gap.


Neural processes during response inhibition in complex posttraumatic stress disorder.
A common feature of complex posttraumatic stress disorder (CPTSD) is impulsivity. Despite the importance of this characteristic in functional difficulties in CPTSD, little is known about its mechanisms. The aim of this study was to identify the distinctive neural profile of CPTSD during attempted inhibition. The present study examined functional alterations in neural networks involved in inhibitory control across functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) paradigms in CPTSD (n = 30), PTSD (n = 40), and healthy control (n = 40) participants who completed a Go/NoGo response inhibition task during separate fMRI and EEG sessions. Brain activations were calculated during the NoGo trials relative to the baseline to evaluate response inhibition functioning. There was reduced bilateral thalamic activation in participants with CPTSD relative to PTSD and controls during inhibition trials, but no activation differences between PTSD and controls for this brain region. There were no differences in functional connectivity between the thalamus and other regions involved in cognitive control between groups. No differences were observed between groups on EEG responses. These findings provide initial evidence of aberrant functioning in the neurocircuitry of inhibitory control, involving the thalamus, in CPTSD. This evidence suggests that CPTSD is distinguished from PTSD by impaired neural processes implicated in response inhibition.


Cushing's disease, pseudo-Cushing states and the dexamethasone test: a historical and critical review.
The dexamethasone (DXM) test has been widely used for diagnosing Cushing's disease (CD). The purpose of this paper is to review its diagnostic merit based on calculation of data extracted from earlier publications. Studies presenting individual values for patients with CD and normal subjects were identified through PubMed searches and references in pertinent studies. Calculation of the retrieved data demonstrated huge variation in the relative suppressibility, negative suppression being common. Furthermore, in almost each study retrieved, the pre and post DXM values were closely correlated. Finally, the generally accepted view that DXM causes less suppression in Cushing's disease than in euadrenal controls appears unfounded. A central issue in the definition of so-called "pseudo-Cushing's states" is failure to suppress cortisol secretion with DXM. From analysis of the literature it appears quite possible that this does not reflect a specific endocrine deficit, but a physiological "stress" reaction. The above issues question the diagnostic value of the test, in particular in clinically and biochemically borderline cases.


Ascending aortic aneurysm repair and surgical ablation for atrial fibrillation.
Although surgical ablation of atrial fibrillation is commonly performed during concomitant coronary or valve surgery, it is still only performed in a fraction these cases when indicated, and less often in patients undergoing aneurysm surgery. We describe our experience in patients undergoing ascending aneurysm repair and concomitant atrial fibrillation ablation. From January 2004 until November 2011, 40 patients underwent ascending aneurysm repair and atrial fibrillation ablation at our institution and were retrospectively analyzed. Average age was 67.6 years (43-85). Root replacement was performed in 23 (57.5 %) and arch replacement with circulatory arrest in 18 (45 %). At an average of 41.8 months, 81 % of patients were in sinus rhythm. Operative survival was 100 %, with 1 and 5 year survival of 97.5 and 93.1 %, respectively. Kaplan-Meier analysis revealed improved overall survival in patients with rhythm success (log-rank test p = 0.037). Aortic aneurysm repair with concomitant atrial fibrillation ablation is safe and efficacious despite the requirement for an already extensive procedure with rhythm success rates similar to those quoted in the setting of other procedures. Successful restoration of sinus rhythm improves long term survival and should be considered in patients presenting with aortic aneurysm and atrial fibrillation.


Evidence for a decline with age in behavioral responsivity to the serotonin agonist, m-chlorophenylpiperazine, in healthy human subjects.
The functional significance of alterations in brain serotonin (5HT) associated with normal aging in both animals and humans is largely unknown. Using the effects of the 5HT agonist, m-chlorophenylpiperazine (m-CPP), as a measure of central serotonergic responsivity, we compared the behavioral and neuroendocrine responses of older normal volunteers (mean age +/- SD = 62.4 +/- 4.12) to those of younger normal volunteers (mean age +/- SD = 31.6 +/- 5.52). When m-CPP was administered intravenously, older subjects showed decreased behavioral responses but similar neuroendocrine responses, compared to younger subjects. The decreased behavioral responsivity was unrelated to pharmaco-kinetic differences between the groups, since m-CPP plasma levels were similar in both groups. This report is the first in vivo study in humans to demonstrate decreased behavioral responsivity with age following serotonergic stimulation, and may indicate a functionally less responsive 5HT subsystem in older subjects.


Mechanisms of selenium inhibition of cell apoptosis induced by oxysterols in rat vascular smooth muscle cells.
Our previous study reported that oxysterol cholestane-3beta,5 alpha, 6 beta-triol (Triol) induced vascular smooth muscle cells (VSMCs) apoptosis, which was inhibited by selenium pretreatment. To further investigate the mechanisms of the inhibition, the glutathione peroxidase (GPx) activity, the total antioxidant capacity (T-AOC), the total superoxide dismutase (SOD) activity, and the level of lipid peroxidation (the content of malondialdehyde, MDA) of VSMCs were measured, and fluidity of cell membrane, reactive oxygen species (ROS) level, the reduction of mitochondrial membrane potential (Delta psi(m)), and the intracellular Ca(2+) in single cell were detected using several fluorescence indicators. Meanwhile, the mRNA levels of c-myc, bcl-2, GPx, and thioredoxin reductase (TR) were measured by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. The results showed that the decrease of GPx activity, T-AOC, SOD activity, the fluidity of cell membrane, the Delta psi(m), and the mRNA expression of c-myc, bcl-2, GPx, and TR of VSMCs and the increase of MDA, ROS generation, and intracellular Ca(2+), significantly induced by Triol (10 microM, 24h) were inhibited to a different extent, respectively, when cells were pretreated with sodium selenite (50 nM, 12 or 24h) before exposure to Triol. These effects were time dependent and enhanced with prolongation of the time of pretreatment. In conclusion, the results in the present work showed that the mechanism of selenium inhibition of cell apoptosis induced by oxysterols in rat VSMCs was related with the antioxidation of selenoproteins.


Prenatal stress and maternal behavior in intact virgin rats: response latencies are decreased in males and increased in females.
The repeated findings that levels of various male-typical behaviors (e.g., copulatory behavior and intermale aggression) are reduced in prenatally stressed (P-S) males, coupled with reports of effects on female physiology and behavior, prompted us to examine the maternal behaviors of P-S animals toward young. Sprague-Dawley female rats were timed-mated (+ sperm = Day 1). From Gestation Days 15 to 22 experimental females were subjected to heat and restraint stress. Control females remained undisturbed throughout pregnancy. The offspring, as adults, were assessed for maternal behavior. P-S males exhibited a significantly shorter latency (in days) to show full maternal behavior (FMB) than Control males, median = 5.0 vs 8.0, respectively. P-S females, on the other hand, exhibited a significantly longer latency than Control females to show FMB (7.0 vs 3.0, respectively). as well as longer latencies to retrieve one, two, or three pups, to begin to crouch over pups, and to build nests in response to young. Sex differences were apparent between Control males and Control females (females were more responsive to young). In contrast, P-S males and Control females exhibited similar latencies to show components of FMB (3-5 days), as did P-S females and Control males (7-9 days). These data demonstrate, therefore, that prenatal stress eliminates the sex difference normally observed in pup-induced maternal behavior. Moreover, the data suggest that prenatal stress renders the male's responsiveness to young more "female-like," while conversely rendering the response of the female more "male-like."


Prevalence and correlates for school truancy among pupils in grades 7-10: results from the 2004 Zambia Global School-based Health Survey.
There are limited data on the prevalence and associated factors of truancy in southern Africa. Yet truancy should attract the attention of public health professionals, educators and policy makers as it may be associated with adolescent problem behaviours. The objectives of the study were to estimate the prevalence and determine correlates of school truancy among pupils in Zambia. We used data collected in 2004 in the Zambia Global School-based Health Survey. Logistic regression analysis was conducted to identify factors associated with truancy. A total of 2257 pupils participated in the survey of whom 53.9% were male. Overall 58.8% of the participants (58.1% of males and 58.4% of females) reported being truant in the past 30 days. Factors associated with truancy were having been bullied (AOR = 1.34, 95% CI [1.32, 1.36]), current alcohol use (AOR = 2.19, 95% CI [2.16, 2.23]), perception that other students were kind and helpful (AOR = 1.12, 95% CI [1.10, 1.14]), being male and being from the lowest school grade. Pupils whose parents or guardians checked their homework (AOR = 0.91 95% CI, [0.89, 0.92]) and those who reported parental supervision (AOR = 0.94, 95% CI [0.92-0.95]) were less likely to report being truant. We found a high prevalence of truancy among pupils in grades 7-10 in Zambia. Interventions aimed to reduce truancy should be designed and implemented with due consideration of the associated factors.


"Quadrature detection for self-mixing interferometry" by Junfeng Wu and Fengfeng Shu: comment.
Some comments about the recently published Optics Letters paper "Quadrature detection for self-mixing interferometry," by Wu and Shu, Opt. Lett.43, 2154 (2018)OPLEDP0146-959210.1364/OL.43.002154, are provided.


A Commentary on the Misalignment of Teacher Education and the Need for Classroom Behavior Management Skills.
Teachers' skill in fostering students' engagement and limiting disruptive behavior is important for maintaining a safe, productive, and effective learning environment. Yet, teachers lacking specific training in classroom and behavior management continue to report high levels of stress and are more likely to leave the profession (Ingersoll, Merrill, et al., Seven trends: The transformation of the teaching force, 2018; Zabel & Zabel, Journal of Special Education Leadership, 15(2), 67-73, 2002). Despite wide agreement from experts about the importance of developing classroom and behavior management skills, many teacher training programs do not require specified coursework or experiences to develop this skill set for teacher licensure or degree completion. In this article, we describe what we observe to be a disconnect between current requirements of teacher preparation programs, and the nature of adequate teacher training to appropriately manage and support student behavior. We argue that this disconnect currently contributes to a host of problematic outcomes observable in schools, including teacher attrition, racial disproportionality in discipline actions, and an overreliance on punitive and ineffective behavior support practices. We end our discussion with additional recommendations for improving teacher training and ensuring systems alignment.


Failed up-regulation of the inhibitory IgG Fc receptor Fc gamma RIIB on germinal center B cells in autoimmune-prone mice is not associated with deletion polymorphisms in the promoter region of the Fc gamma RIIB gene.
FcgammaRIIB, a low-affinity FcR for IgG, inhibits BCR-mediated activation when these two receptors are co-cross-linked by Ags and IgG-containing immune complexes. Although a role for FcgammaRIIB in the germinal center (GC) reaction has been proposed, conflicting results have been published regarding the levels of FcgammaRIIB expressed on GC B cells in normal and autoimmune-prone mice and humans. In the present study, we investigate this issue in detail in mice by using multiple GC B cell markers, two different antigenic systems, primary and secondary GC responses, and by excluding the influence of splenic influx of immature B cells and passive acquisition of FcgammaRIIB from follicular dendritic cells. Our results are in concordance with previous data indicating that FcgammaRIIB expression is up-regulated on GC B cells in normal mice. In contrast, we observe comparable levels of FcgammaRIIB on GC and non-GC B cells in New Zealand White, New Zealand Black, and B6.Sle1 autoimmune-prone strains. Therefore, we suggest that these strains exhibit failed up-regulation of FcgammaRIIB on GC B cells, rather than down-regulation, as previously suggested. Also, in contrast to previous indications, this perturbed regulation is not uniquely associated with deletion polymorphisms in the promoter region of the FcgammaRIIB gene but does appear to be independent of genetic background. Finally, we present evidence indicating that FcgammaRIII, a low-affinity activating IgG FcR, is expressed on the GC B cells of normal but not autoimmune-prone mice.


Global PM2.5 and secondary organic aerosols (SOA) levels with sectorial contribution to anthropogenic and biogenic SOA formation.
This study estimates global PM2.5 and anthropogenic and biogenic Secondary Organic Aerosols (a-SOA and b-SOA) and sources contributing to their formation. The global landscape was divided into eleven domains (North America (NAM); South America (SAM); Europe (EUR); North Africa and Middle East (NAF); Equatorial Africa (EAF); South of Africa (SAF); Russia and Central Asia (RUS); Eastern Asia (EAS); South Asia (SAS); Southeast Asia (SEA) and Australia (AUS)) and 46 cities based on varying populations. Three inventories for global emissions were considered: Community Emissions Data System, Model of Emission of Gases and Aerosol, and Global Fire Emissions Database. WRF-Chem model coupled with atmospheric reactions and the secondary organic aerosol model was employed for estimating PM2.5, a-SOA, and b-SOA for 2018. No city attained WHO's annual PM2.5 guideline of 5 μg/m3. Delhi, Dhaka, and Kolkata (63-92 μg/m3) in south Asia were the most polluted, and seven cities (mostly in EUR and NAM) met the WHO target IV (10 μg/m3). The highest SOA levels (2-9 μg/m3) were in the cities of SAS and Africa, but with a low SOA contribution to PM2.5 (3-22%). However, the low levels of SOA (1-3 μg/m3) in EUR and NAM had a higher contribution of SOA to PM2.5 (20-33%). b-SOA were consistent with the region's vegetation and forest cover. The SOA contribution was dominated by residential emissions in all domains (except in the NAF and AUS) (maximum in SAS). The non-coal industry was the second highest contributor (except in EAF, NAF, and AUS) and EUR had the maximum contribution from agriculture and transport. Globally, residential and industry (non-coal and coal) sectors showed the maximum contribution to SOA, with a-SOA and b-SOA being nearly equal. Ridding of biomass and residential burning of solid fuel is the single most action benefiting the PM2.5 and SOA concerns.


[Perioral dermatitis].
The cause of perioral dermatitis remains unclear. It is not due to the application of fluorinated corticosteroids. For therapy Locoid cream and tetracycline are recommended. There are some cases which are not influenced by any therapy. In these cases psychotherapy is sometimes effective.


Terbutaline in myasthenia gravis: a pilot study.
The objective of this study was to assess the short-term efficacy and safety of terbutaline, a beta2-adrenergic agonist, in patients with myasthenia gravis (MG) in a randomized, double-blind, placebo-controlled, crossover study. The primary endpoint for efficacy was a reduction of at least 3 points in the quantitative MG score (QMGS). Secondary endpoints included changes in the functional disability scale (FDS), forced vital capacity (FVC), grip strength, anti-acetylcholine receptor (AChR) antibody levels and decremental response. During the terbutaline phase, five of eight (63%) patients had an improvement in the QMGS of 3.0 or greater, while 3/8 (38%) patients had improvement in the FDS of one grade. No improvement was seen during the placebo period. Statistical analysis using Wilcoxon signed-rank test confirmed that terbutaline treatment resulted in a significant improvement in QMGS. There was no change in FVC, grip strength or anti-AChR antibody levels, but there was an improvement in the decremental response during terbutaline phase. Terbutaline was well-tolerated in all study subjects. We conclude that terbutaline may be an effective adjunct therapy in a subset of patients with myasthenia, although confirmation with larger trials will be required.