Lack of association between TTV viral load and aminotransferase levels in patients with hepatitis C or non-B-C.
TT virus (TTV) is a newly identified un-enveloped single-stranded DNA virus. Although TTV was initially thought to be a new hepatitis virus, it is still unclear whether it causes hepatitis. To clarify the natural history and pathogenesis of TTV infection, serial serum samples from patients with chronic hepatitis were analysed. TTV DNA was quantified by real-time detection polymerase chain reaction assay (RTD-PCR), which was adapted for TTV. Five patients with chronic hepatitis, 4 with hepatitis C and 1 with non-B-C, were studied. The study period ranged from 9 to 50 months. In 3 patients there were frequent increases in TTV DNA titres, but no concomitant elevation of the aminotransferase (ALT) levels. In 2 patients who were treated with interferon, the changes in TTV titres were not synchronized with those of the ALT levels. Thus, in cases of chronic hepatitis, no correlation was observed between the serum TTV DNA titres and the ALT levels.


Differential role of NSs genes in the neurovirulence of two genogroups of Akabane virus causing postnatal encephalomyelitis.
Akabane virus (AKAV) is a member of the genus Orthobunyavirus, family Peribunyaviridae. In addition to AKAV strains that cause fetal Akabane disease, which is characterized by abortion in ruminants, some AKAV strains cause postnatal infection characterized by nonsuppurative encephalomyelitis in ruminants. Here, we focused on the NSs protein, a virulence factor for most viruses belonging to the genus Orthobunyavirus, and we hypothesized that this protein would act as a neurovirulence factor in AKAV strains causing postnatal encephalomyelitis. We generated AKAV strains that were unable to produce the NSs protein, derived from two different genogroups, genogroups I and II, and then examined the role of their NSs proteins by inoculating mice intracerebrally with these modified viruses. Our results revealed that the neurovirulence of genogroup II strains is dependent on the NSs protein, whereas that of genogroup I strains is independent of this protein. Notably, infection of primary cultured bovine cells with these viruses suggested that the NSs proteins of both genogroups suppress innate immune-related gene expression with equal efficiency. These results indicate differences in the determinants of virulence of orthobunyaviruses.


Structural relationships between measures based on heart beat intervals: potential for improved risk assessment.
Decreased left ventricular ejection fraction is the most commonly used risk factor for identification of patients at high-risk for lethal ventricular arrhythmic events. Twenty-four-hour electrocardiographic (ECG) approaches to risk stratification include: counts of ventricular premature contractions (VPCs), measures of heart rate variability (HRV), and heart rate turbulence (HRT) which has two components, turbulence onset and turbulence slope (TS). Refinement of these ECG risk stratifiers could enhance their clinical utility. We explored the structural relationships between heart rate (HR) and HRV and HRT measures. Our goal was to separate out the component of these measures due to the underlying average heart rate (HR), thus potentially reducing the variability of the measures and increasing their power to stratify risk. We proposed re-scaling tachograms of heart-beat intervals so that the re-scaled tachogram has a HR of 75 (or equivalently an average interval of 800 ms) and calculating HRV and HRT from the rescaled time series. We also explored the relationship between the number of VPCs and HRT. We showed that TS is structurally related to the number of VPCs (and hence to the length of the ECG recording). We proposed an adjusted TS that is independent of the number of VPCs. We also addressed the ability of shorter ECG recording to estimate HRV and HRT measures. We evaluated standard and rescaled HRV and HRT measures using qualifying ambulatory ECG recordings from 744 patients in the Cardiac Arrhythmia Suppression Trial. We found that measures based on the rescaled tachogram had reduced variance (20% to 40%). Correlations between measures were also substantially reduced. We also found substantial circadian effects on some, but not all HRV indices, not explained by the circadian pattern in HR and possibly pointing to additional measures for risk prediction. In conclusion, we found that adjusting for HR and the number of VPCs in heart-beat related ambulatory ECG measures has the potential to significantly improve the power of these measures to risk stratify cardiac patients.


Measuring human papillomavirus (HPV) vaccination coverage and the role of the National HPV Vaccination Program Register, Australia.
Accurate estimates of HPV vaccination coverage are critical for determining the proportion of the target female population that is not protected by the vaccine, as well as for monitoring the performance of vaccine delivery programs. The implementation of an HPV vaccination register, either as part of an existing immunisation register or stand-alone, can add substantial benefits to an HPV vaccination program. In Australia, the National HPV Vaccination Program Register supports the HPV vaccination program by providing information to consumers and providers about incomplete courses as well as estimates of vaccination coverage by age and area. Future monitoring of vaccine effectiveness will be facilitated by cross-linking to Pap test registries.


Quantification of sulfatides and lysosulfatides in tissues and body fluids by liquid chromatography-tandem mass spectrometry.
Sulfatides are found in brain as components of myelin, oligodendrocytes, and neurons but are also present in various visceral tissues. Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disorder caused by a deficiency of arylsulfatase A, leading to severe white matter disease due to the accumulation of sulfatides and lysosulfatides. To study the physiological role of sulfatides, accessible and sensitive quantitative methods are required. We developed a sensitive LC/MS/MS method to quantify total sulfatide and lysosulfatide content as well as individual molecular species in urine and plasma from MLD patients and plasma and tissues from an MLD mouse model. Our results demonstrate that the method can quantify a wide range of sulfatide concentrations and can be used to quantify total sulfatide content and levels of individual molecular species of sulfatides in tissues, cells, and body fluids. Even though plasma sulfatides and lysosulfatides would seem attractive candidate biomarkers that could possibly correlate with the severity of MLD and be of use to monitor the effects of therapeutic intervention, our results indicate that it is unlikely that the determination of these storage products in plasma will be useful in this respect.


[Influence of nutritional patterns on the severity of acne in young adults].
Currently, one of discussed questions of acne etiopathogenesis is alimentary factors, in particular, national dietary habits at different regions and the role of diet. The purpose of this research: from the standpoint of evidence-based medicine to reveal the influence of dietary intake (energy value of the diet, macro- and micronutrients content) on the actual severity of acne in young people. We observed 180 respondents aged 15 to 25 years. The main group included 90 patients with moderate to severe acne, who were treated at the Center for Dermatology and prevention of sexually transmitted diseases in Astana, including 38 girls and 52 boys, mean age 20.5 +/- 4.3 years. The control group consisted of 90 apparently healthy subjects (36 girls and 54 boys, mean age 19.8 +/- 4.2 years) without even a single manifestation of non-inflammatory or inflammatory acne elements. Studying the actual food consumption was carried out by a 24-hour (daily) food recall using specially designed questionnaires and albums. regular meals with excess energy value significantly contributes to the progression of disease severity in young people with acne [the power of influence in young men was 0.43 (43%), girls--0.42 (42%)], the excess of the normal daily requirements for carbohydrates also significantly affect the severity of acne [the power of influence in young men--0.23 (23%), in girls--0.35 (35%)], lack of vitamin A (retinol) and its provitamin (carotene) significantly affect the severity of acne (the power of influence in young men--0.44 (44%) and 0.42 (42%), respectively, in girls--0.46 (46%) and 0.31 (31%), respectively); in young men with severe acne vitamin D deficiency with a force of 0.3 (30%) significantly potentiates the inflammatory process; lack of zinc in the diet significantly affects the severity of the pathological process in severe forms of acne, the power of influence of this micronutrient in young men--0.44 (44%), women--0.34 (34%).


Dose-response relationship between opioid use and adverse effects after ambulatory surgery.
This health outcomes analysis based on data from a randomized, double-blind, placebo-controlled trial determined dose-response relationship between opioid use and related symptoms. All patients received intravenous fentanyl on demand for pain predischarge, and oral acetaminophen 500 mg/hydrocodone 5 mg every 4-6 hours as needed postdischarge for up to 7 days postsurgery. Patients completed an opioid-related Symptom Distress Scale (SDS) questionnaire every 24 hours postdischarge for 7 days, which assessed 12 opioid-related symptoms by 3 ordinal measures: frequency, severity, and bothersomeness. Clinically meaningful events (CMEs) were defined based on the responses to this questionnaire. Opioid use was converted to morphine equivalent dose (MED). The dose-response relationship between composite SDS scores and MED on Day 1, on Days 0 and 1, and on Days 1-4, was assessed. SDS scores for all 12 symptoms within the 3 dimensions were significantly associated with MED on Day 1 (F-value=1.56; P=0.04), as well as cumulative MED used on Days 0 and 1 (F-value=1.85; P<0.01). Patients with a specific CME used a higher MED than those without a CME on Day 1 (P<0.001). Between Days 1 and 4, patients with a higher number of patient-CME-days used a significantly higher MED. Regression analyses suggested that once the MED reached a threshold, approximately every 4 mg increase in MED was related to 1 additional patient-CME-day (P<0.01). A dose-response relationship empirically exists between MED and directly assessed opioid-related CMEs after ambulatory laparoscopic cholecystectomy. Once daily MED reaches a threshold, every 3-4 mg increase will be associated with 1 additional clinically meaningful opioid-related symptom, or 1 additional patient-day with an opioid-related CME.


The effect of various menopausal hormone therapies on markers of inflammation, coagulation, fibrinolysis, lipids, and lipoproteins in healthy postmenopausal women.
Androgenic progestins such as norethisterone acetate (NETA) may influence the effect of estradiol (E(2)) therapy. We compared the influence of oral E(2), with and without NETA, and transdermal E(2) on markers of coagulation, fibrinolysis, and inflammation and on lipids and lipoproteins in healthy postmenopausal women. A total of 112 healthy postmenopausal women were randomized to receive treatment with either oral E(2), with or without NETA, transdermal E(2), or placebo. At baseline and after 28 weeks, levels of serum lipids and lipoproteins and markers of coagulation, fibrinolysis, and inflammation were determined. Of the fibrinolytic parameters, oral E(2) (P < 0.05) and E(2) with NETA (P < 0.01) shortened euglobulin clot lysis time. Oral E(2) decreased plasminogen activator inhibitor-1 activity (P < 0.05). Oral E(2) with NETA reduced plasminogen activator inhibitor-1 antigen levels (P < 0.01) and increased D-dimer antigen levels (P < 0.001). All three modes of menopausal hormone therapy reduced tissue type plasminogen activator antigen. Of the coagulation parameters, both routes of E(2) therapy decreased fibrinogen levels (P = 0.002 for oral and P = 0.007 for transdermal E(2)), whereas E(2) with NETA showed no effect. The decrease of fibrinogen was larger after oral E(2) (P = 0.02). Oral E(2) with NETA reduced antithrombin III (P < 0.001) and protein C (P < 0.001) activity. Oral E(2) (P = 0.04) and E(2) with NETA (P < 0.01) increased C-reactive protein (CRP). Transdermal E(2) showed no influence on CRP. The addition of NETA influenced the change in CRP, as the increase in CRP was more pronounced after E(2) without NETA (P = 0.005). The levels of serum amyloid A, interleukin-6, and tumor necrosis factor-alpha did not change significantly after any of the modes of hormone therapy. Of the lipids and lipoproteins, oral E2 decreased low-density lipoprotein cholesterol (P < 0.01), lipoprotein (a) (P < 0.05), and increased high-density lipoprotein cholesterol (P < 0.05). Transdermal E(2) decreased triglycerides (P < 0.02) and increased high-density lipoprotein cholesterol (P < 0.03). Oral E(2) with NETA decreased total cholesterol (P < 0.01) and high-density lipoprotein cholesterol (P < 0.005). Oral E(2), with or without NETA, produced no net activation of coagulation but improved fibrinolysis. Both modes of oral menopausal hormone therapy have a greater impact on markers of inflammation, coagulation, fibrinolysis, lipids, and lipoproteins than transdermal E(2). NETA attenuates some E(2) effects. Further studies are needed to elucidate the impact of these effects on clinical endpoints.


[CT scanning in the diagnosis and treatment of intraorbital dermoid cyst].
39 cases of intraorbital dermoid cyst were examined by CT scanning with characteristic features of heterogeneity in the cystic content with areas of negative CT value, nonenhancement by contrast media, and excavation of the orbital walls. The precise localization of the tumor is conducive to the selection of a proper surgical approach.


Failure of bland soap handwash to prevent hand transfer of patient bacteria to urethral catheters.
The study was designed to compare the efficacies of bland soap handwash and isopropyl alcohol hand rinse in preventing transfer of aerobic gram-negative bacilli to urinary catheters via transient hand colonization acquired from direct patient contact. Glove juice recovery of gram-negative bacteria was considered transient colonization; catheter recovery was considered transfer colonization. The contact source for gram-negative bacteria was a single "high burden" groin skin carrier (greater than or equal to 10(4)/ml cup scrub fluid). Using a two-period cross-over design, 6 healthcare workers had 2 15-second contacts for each hand followed by either soap handwash or alcohol hand rinse (12 experiments with each treatment). Between 4 to 5 minutes after contact, each hand manipulated a catheter; the catheter was then cultured and the hand was glove juice tested. Soap handwash failed to prevent gram-negative bacteria transfer to the catheter in 11 of 12 (92%) experiments; alcohol hand rinse in 2 of 12 (17%) (p less than .001). Soap handwash failed to prevent transient colonization in 12 of 12 (100%) experiments; alcohol in 5 of 12 (42%) (risk ratio 2.4, 95% confidence interval 1.2-4.7). Single gram-negative bacteria species carried at source levels greater than or equal to 5.5 x 10(3)/ml (heavy contamination) established transient colonization in 23 of 30 (77%) exposures following soap handwash; single gram-negative bacteria species carried at levels less than or equal to 3.5 x 10(3)/ml established colonization in 1 of 22 (5%) similar exposures (p less than .001). Bland soap handwash was generally ineffective in preventing hand transfer of gram-negative bacteria to catheters following brief contact with a heavy-contamination patient source; alcohol hand rinse was generally effective.


Induction of nitric oxide synthase in mouse dendritic cells by IFN-gamma, endotoxin, and interaction with allogeneic T cells: nitric oxide production is associated with dendritic cell apoptosis.
Nitric oxide (NO) is an important effector molecule that is involved in immune regulation and host defense. In this study, highly purified NLDC 145+ (DEC-205+) MHC class II(bright) B7-2+ dendritic cells (DC) propagated from normal mouse bone marrow in response to granulocyte-macrophage CSF + IL-4 were induced to produce NO by IFN-gamma and LPS. NO production was inhibited by the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (NMMA). Nitrite also accumulated in mixed leukocyte culture supernatants as the result of coculture of DC with purified naive allogeneic T cells. Furthermore, NO production was induced by CD40 ligation. Suboptimal T cell proliferation observed at high relative concentrations of DC correlated with increased NO production and was mitigated by NMMA. Induction of mRNA for an inducible NOS (iNOS) in DC was confirmed by Northern blotting, whereas intracellular iNOS was visualized by two-color flow cytometry and by both immunofluorescent and immunogold labeling in a subpopulation of IFN-gamma + LPS-stimulated cells. Both endogenous NO production and exposure of unstimulated DC to the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) resulted in DC apoptosis. Thus, although DC function initially as the most potent APCs for T cell activation, DC induced to synthesize NOS by IFN-gamma may inhibit (allogeneic) T cell proliferation: NO may suppress lymphocyte proliferation and also induce apoptosis of the most potent source of alloantigenic stimulation.


[Importance of morphostructural changes observed in cortical micro-vessels in patients who died after a severe head injury].
The development of secondary lesions in traumatic head injuries seems to be a determinative factor for the survival of these patients. Endothelium damage of cortical microvessels could be fundamental in the main secondary lesions as cerebral ischemia and intracranial hypertension. To investigate which are the main morphological changes that can be observed in cortical microvessels from these patients. We have studied 15 fresh human brains from subjects died after a severe head injury. The study has been carried out by scanning electron microscopy of vascular corrosion casts and confocal microscopy of histological sections after immunocytochemistry, as well as detection of apoptosis by TUNEL technique. The most significant structural alterations were observed mainly on arterioles and capillaries of the middle and deep vascular zones of the cerebral cortex. Corrosion casts showed vessels with longitudinal folds, sunken surface with craters and flattened vessels with reduced lumen. Histological sections immunostained with MAS-336 also showed vessels with longitudinal folds and thinning of their vascular lumen, the presence of cytoplasmic round bodies and a thickening of endothelial cell membrane. TUNEL method revealed a positive staining of some endothelial cells. The structural alterations observed seem to reveal a situation of cellular damage of endothelium in the human cortical microvessels from these patients. It can be thought that this kind of lesions, as well as the secondary functional injury of the blood brain barrier, could play an important role in the development of secondary damage.


Liposomes as siRNA delivery vectors.
Nucleic Acid Based Drugs (NABDs) constitute a class of promising and powerful therapeutic new agents with limited side effects, potentially useable against a wide range of diseases, including cancer. Among them, the short interfering RNAs (siRNAs), represent very effective molecules. Despite their in vitro efficacy, the major drawback that limits siRNAs usage consists in a difficult delivery due to their very low stability in physiological fluids, and to their limited membrane-permeability through physiological barriers. On the other hand, the liposomes (lipid bilayers closed in vesicles of various sizes) represent interesting drug delivery systems (DDSs) which can be tailored in order to get the best performance in terms of load, vesicle size and transfection yield. In this work, the current state of study in these two fields, and the connections between them, are briefly summarized.


Vitamin B12 deficiency in children: a treatable cause of neurodevelopmental delay.
Vitamin B12 deficiency in children can rarely cause neurologic manifestations. In this series, 14 pediatric cases (median age 11 months) have been described in whom association of vitamin B12 deficiency with developmental delay or regression was observed. Severe to profound delay was present in 8 (57%) patients. All the patients were exclusively or predominantly breast-fed and 10 of 12 mothers had low serum vitamin B12 levels. Three to 6 months after treatment, a mean gain of development quotient of 38.8 points was seen in 7 follow-ups. In settings with a high prevalence of vitamin B12 deficiency, this association should be actively searched for.


A3 receptor agonist, Cl-IBMECA, potentiate glucose-induced insulin secretion from MIN6 insulinoma cells possibly through transient Ca2+ entry.
Diabetes incidence showed ascending trends in recent years indicating urgent need for new therapeutic agents. Extracellular adenosine signaling showed promising results. However, role of its A3 receptor in pancreatic β-cells proliferation and insulin secretion is not well established. Thus, we aimed to determine its main signaling mediators in MIN6 insulinoma cell line. A3 adenosine receptor (A3AR) expression was confirmed using RT-PCR. Receptor functionality was evaluated by measurements of cAMP, using ELISA kit, and intracellular Ca2+ levels, using Fura 2/AM probe in response to the specific A3AR agonist (Cl- IBMECA). Insulin ELISA kit was used to measure insulin release. Herein, we mentioned that MIN6 cells express active form of A3AR, which decreased cAMP levels with the half maximal effective concentration (EC50) value of 5.61. [Ca2+]i Levels transiently (approximately 120 sec) increased in response to the agonist. Cl-IBMECA increase insulin secretion at 0.01-1 μM, but showed an inhibitory effects at higher concentrations (1-10 μM). Altogether, we found that in MIN6 cells, A3AR, possibly through Ca2+ mediated signaling pathways, potentiated glucose-induced insulin secretion.


Preconditioning against renal ischaemia reperfusion injury: the failure to translate to the clinic.
Acute kidney injury (AKI) as a result of ischaemia-reperfusion represents a major healthcare burden worldwide. Mortality rates from AKI in hospitalized patients are extremely high and have changed little despite decades of research and medical advances. In 1986, Murry et al. demonstrated for the first time the phenomenon of ischaemic preconditioning to protect against ischaemia-reperfusion injury (IRI). This seminal finding paved the way for a broad body of research, which attempted to understand and ultimately harness this phenomenon for human application. The ability of preconditioning to limit renal IRI has now been demonstrated in multiple different animal models. However, more than 30 years later, a safe and consistent method of protecting human organs, including the kidneys, against IRI is still not available. This review highlights agents which, despite strong preclinical data, have recently failed to reduce AKI in human trials. The multiple reasons which may have contributed to the failure to translate some of the promising findings to clinical therapies are discussed. Agents which hold promise in the clinic because of their recent efficacy in preclinical large animal models are also reviewed.


Near intron positions are reliable phylogenetic markers: an application to holometabolous insects.
Today, the reconstruction of the organismal evolutionary tree is based mainly on molecular sequence data. However, sequence data are sometimes insufficient to reliably resolve in particular deep branches. Thus, it is highly desirable to find novel, more reliable types of phylogenetic markers that can be derived from the wealth of genomic data. Here, we consider the gain of introns close to older preexisting ones. Because correct splicing is impeded by very small exons, nearby pairs of introns very rarely coexist, that is, the gain of the new intron is nearly always associated with the loss of the old intron. Both events may even be directly connected as in cases of intron migration. Therefore, it should be possible to identify one of the introns as ancient (plesiomorphic) and the other as novel (derived or apomorphic). To test the suitability of such near intron pairs (NIPs) as a marker class for phylogenetic analysis, we undertook an analysis of the evolutionary positions of bees and wasps (Hymenoptera) and beetles (Coleoptera) in relation to moths (Lepidoptera) and dipterans (Diptera) using recently completed genome project data. By scanning 758 putatively orthologous gene structures of Apis mellifera (Hymenoptera) and Tribolium castaneum (Coleoptera), we identified 189 pairs of introns, one from each species, which are located less than 50 nt from each other. A comparison with genes from 5 other holometabolan and 9 metazoan outgroup genomes resulted in 22 shared derived intron positions found in beetle as well as in butterflies and/or dipterans. This strongly supports a basal position of hymenopterans in the holometabolous insect tree. In addition, we found 31 and 12 intron positions apomorphic for A. mellifera and T. castaneum, respectively, which seem to represent changes inside these branches. Another 12 intron pairs indicate parallel intron gains or extraordinarily small exons. In conclusion, we show here that the analysis of phylogenetically nested, nearby intron pairs is suitable to identify evolutionarily younger intron positions and to determine their relative age, which should be of equal importance for the understanding of intron evolution and the reconstruction of the eukaryotic tree.


[Clinical analysis of 5 cases of endobronchial hamartoma].
Objective: To analyze the clinical manifestations of patients with endobronchial hamartoma(EH),and therefore to improve understanding of the disease. Methods: Data were retrospectively reviewed to describe the clinical characteristics, diagnosis procedures and prognosis of EH, including 5 patients in Beijing Anzhen Hospital, Capital Medical University from Jun 2007 to Feb 2018 and another 159 patients from Chinese and English literatures published after Jan 2000. Results: The five patients, 4 males and 1 female, aged from 46 to 69 years[mean (56±7) years], were diagnosed with EH in our hospital. There was no fever in the 5 cases, cough and expectoration in 4 cases, hemoptysis in 3 cases and asymptomatic in 1 case. Chest CT revealed that the lesions of all 5 cases were located in the right bronchial tube; 3 as high-density endobronchial mass, 1 as low-density mass, 1 as mixed density mass, and 1 as a "popcorn" lesion. Three cases were accompanied by obstructive pneumonia in the distal part of the EH and 2 cases by atelectasis. CT enhanced scan was performed in 5 cases, 2 showing no enhancement and 3 showing mild enhancement. Four cases showed polyposis under bronchoscopy, and 5 cases received bronchoscopic biopsy with 3 pathologically diagnosed as EH. Four of them received lobectomy, while 1 received removal by biopsy forceps, and all were pathologically confirmed as EH. There was no evidence of recurrence in these 5 patents with follow-up. Conclusions: EH was a rare benign bronchial tumor with nonspecific clinical and imaging manifestations. Endobronchial polyposis could be revealed by bronchoscopy, and pathological study is required to confirm the diagnosis.


Early detection of tumor cells by innate immune cells leads to T(reg) recruitment through CCL22 production by tumor cells.
In breast carcinomas, patient survival seems to be negatively affected by the recruitment of regulatory T cells (T(reg)) within lymphoid aggregates by CCL22. However, the mechanisms underpinning this process, which may be of broader significance in solid tumors, have yet to be described. In this study, we determined how CCL22 production is controlled in tumor cells. In human breast carcinoma cell lines, CCL22 was secreted at low basal levels that were strongly increased in response to inflammatory signals [TNF-α, IFN-γ, and interleukin (IL)-1β], contrasting with CCL17. Primary breast tumors and CD45(+) infiltrating immune cells appeared to cooperate in driving CCL22 secretion, as shown clearly in cocultures of breast tumor cell lines and peripheral blood mononuclear cells (PBMC) or their supernatants. We determined that monocyte-derived IL-1β and TNF-α are key players as monocyte depletion or neutralization of these cytokines attenuated secretion of CCL22. However, when purified monocytes were used, exogenous human IFN-γ was also required to generate this response suggesting a role for IFN-γ-producing cells within PBMCs. In this setting, we found that human IFN-γ could be replaced by the addition of (i) IL-2 or K562-activated natural killer (NK) cells or (ii) resting NK cells in the presence of anti-MHC class I antibody. Taken together, our results show a dialogue between NK and tumor cells leading to IFN-γ secretion, which in turn associates with monocyte-derived IL-1β and TNF-α to drive production of CCL22 by tumor cells and subsequent recruitment of T(reg). As one validation of this conclusion in primary breast tumors, we showed that NK cells and macrophages tend to colocalize within tumors. In summary, our findings suggest that at early times during tumorigenesis, the detection of tumor cells by innate effectors (monocytes and NK cells) imposes a selection for CCL22 secretion that recruits T(reg) to evade this early antitumor immune response.


The Walking Trail-Making Test is an early detection tool for mild cognitive impairment.
Executive function impairment (in particular, mental flexibility) in the elderly, and in patients with mild cognitive impairment (MCI), is strongly correlated with difficulties in performing complex walking tasks. The aim of this study was to determine if the adaptation of a neuropsychological test (the Trail-Making Test), to evaluate executive functions during walking, can be an early detection tool for cognitive impairment. Fifty subjects (15 young, 20 older, presumably healthy, and 15 MCI) were first evaluated for cognitive functions (Mini-Mental State Examination, Frontal Assessment Battery, and Trail-Making Test) and motor functions (10-meter walking test). All subjects then performed a spatial navigation, or a complex walking test (the Walking Trail-Making Test: [WTMT]), and their spatiotemporal walking variables were analyzed using cluster analysis. Following evaluation of WTMT locomotor performance, cluster analysis revealed three groups that were distinctly different in age and cognitive abiliTIES: a group of young subjects, a group of healthy older subjects, MCI subjects with amnestic impairment, and a group of MCI subjects with executive function impairment. The WTMT enabled early detection, (ie, borderline MCI) of dysexecutive impairment, with 78% sensitivity and 90% specificity. The WTMT is of interest in that it can help provide early detection of dysexecutive cognitive impairment.


Survey of bereaved parents.
A retrospective study in Vancouver was designed to evaluate parents' perceptions of support received after the death of a child up to 5 years old. The families were contacted with the help of health care professionals and the news media. A standardized questionnaire was used in a personal interview or occasionally by mail. The contact with health care professionals after the child's death was frequently considered by the 61 families not to have been helpful: 80% of the families judged the information or counselling they had received to be inadequate, and over 50% had received none; many listed comments and behaviour that they considered harmful. The families desired both full medical information and grief support; what forms such support could take are suggested.


Reaching low-income women at risk of AIDS: a case history of a drop-in center for women in the South Bronx, New York City.
The Women's Drop-In Center, sponsored by a church with an active social ministry, offered education and support to African-American and Latina women at risk of HIV infection in a low-income community in New York City. Peer educators were trained to provide information, counseling and referrals on substance abuse, sexuality, HIV infection and related issues. The drop-in center offered a safe space for participants to discuss common concerns, learn about community resources and support each others' efforts to protect their health. Based on an evaluation that included quantitative and qualitative measures of changes in participating individuals and organizations, it is suggested that grass-roots community organizations can play an important role in AIDS prevention but they may need additional resources to sustain the intensive interventions that are likely to lead to lasting changes in neighborhoods with other significant social problems.


Katabatic winds diminish precipitation contribution to the Antarctic ice mass balance.
Snowfall in Antarctica is a key term of the ice sheet mass budget that influences the sea level at global scale. Over the continental margins, persistent katabatic winds blow all year long and supply the lower troposphere with unsaturated air. We show that this dry air leads to significant low-level sublimation of snowfall. We found using unprecedented data collected over 1 year on the coast of Adélie Land and simulations from different atmospheric models that low-level sublimation accounts for a 17% reduction of total snowfall over the continent and up to 35% on the margins of East Antarctica, significantly affecting satellite-based estimations close to the ground. Our findings suggest that, as climate warming progresses, this process will be enhanced and will limit expected precipitation increases at the ground level.


Recent developments in the management of patients at risk for sudden cardiac death.
Sudden cardiac death (SCD) due to ventricular tachyarrhythmias is an important cause of mortality in the United States, 4% of which occurs in patients with structurally normal hearts. At least some arrhythmias are caused by ≥ 1 mutation in 1 of the genes that control electrical conduction through the heart by altering calcium homeostasis or depolarization or repolarization gradients in the ventricle. Although SCD may be the first presentation, patients may often present with symptoms of palpitations or hemodynamic compromise, such as dizziness, seizure, or syncope, particularly following exertion. They may also be made aware of possibly having the condition due to symptoms in other family members. The primary care physician is ideally placed to investigate these symptoms, including detailed clinical and family histories and examining the baseline electrocardiogram. In all inherited cardiac death syndromes, first-degree relatives should be referred to a cardiologist, and should undergo testing appropriate for the condition. While management of patients at risk of SCD largely centers on risk stratification and, if necessary, insertion of an implantable cardioverter-defibrillator, there are a number of other treatments being developed. β-Blockers are often very effective in preventing arrhythmic episodes associated with catecholaminergic polymorphic ventricular tachycardia and some subtypes of long QT syndrome. In certain situations, calcium channel blockers may also be used. Quinidine and isoproterenol can be useful in treating Brugada syndrome. Left cervicothoracic stellectomy may occasionally be used in the treatment of long QT syndrome. As the genetic basis of these diseases becomes known, genetic testing is forming an increasingly important part of diagnosis, and gene-specific therapy is an area under investigation.


Direct Decarboxylation of Trifluoroacetates Enabled by Iron Photocatalysis.
Trifluoroacetates are the most abundant and accessible sources of trifluoromethyl groups, which are key components in pharmaceuticals and agrochemicals. The generation of trifluoromethyl reactive radicals from trifluoroacetates requires their decarboxylation, which is hampered by their high oxidation potential. This constitutes a major challenge for redox-based methods, because of the need to pair the redox potentials with trifluoroacetate. Here we report a strategy based on iron photocatalysis to promote the direct photodecarboxylation of trifluoroacetates that displays reactivity features that escape from redox limitations. Our synthetic design has enabled the use of trifluoroacetates for the trifluoromethylation of more easily oxidizable organic substrates, offering new opportunities for late-stage derivatization campaigns using chemical feedstocks, Earth-abundant catalysts, and visible-light.


Mindfulness and asthma symptoms: A study among college students.
Given the known link between asthma and stress as well as the link between mindfulness and stress, we explore the possible association between trait mindfulness and asthma-related diagnosis and symptoms with a cross-sectional study. In 2014, we surveyed a sample of college students in their freshman year, from a public university in Shanghai, China. We used three multilevel logistic regressions to estimate the association between trait mindfulness (measured by Mindful Awareness Attention Scale, MAAS) and self-report of ever having an asthma diagnosis, ever having had persistent dry cough, and ever having had wheezing symptoms. Age, gender, household registration status, and the frequency of smog in the respondent's hometown were used as control variables in the study. The home province of the student was used as the cluster variable in the multilevel models. Among the 1392 students in the analysis sample (mean age = 18.3), 47 (3.4%) self-reported an asthma diagnosis, 251 (18.1%) reported having had persistent dry cough, and 100 (7.2%) reported having had wheezing symptoms. A one-unit increase in MAAS is negatively associated with having a self-reported asthma diagnosis (Odds Ratio (OR): 0.662, 95% Confidence Interval (CI): 0.452, 0.969, p = 0.034), having had persistent dry cough (OR: 0.658, 95% CI: 0.545, 0.795, p < 0.001), and wheezing (OR = 0.747, 95% CI: 0.569, 0.981, p = 0.036). This is the first study to suggest a link between trait mindfulness and asthma. Our finding provides evidence that people with higher level of mindfulness are less likely to have had an asthma diagnosis and less likely to have the symptoms of persistent dry cough and wheezing.


[Report on the application of chibro-timoptol after one year's use in ophthalmological practice (author's transl)].
A summary is given of the common methods of treating glaucoma medically, beginning with the introduction of pilocarpine over 100 years ago and ending, for the time being, with the application of the beta-blocker Timolol Maleat (Chibro-Timoptol). The authors have been using Chibro-Timoptol for over a year and have treated more than 300 patients by this method so far. Timolol proved to have significant advantages over all other pressure-lowering drugs used in the past. It was just as effective or more effective than the substances used previously. For a newly diagnosed glaucoma, the authors therefore recommend using Timolol in all initial attempts at pressure regulation.


[Heart rate: a risk factor or an epiphenomenon?].
The role of heart rate (HR) as an independent predictor of cardiovascular morbidity and mortality remains controversial. Direct evidence supporting a causal association between HR and prognosis is still lacking even if such relation appears plausible and may be inferred from epidemiological studies and clinical trials with HR lowering agents. The introduction of If current blocking agents, namely ivabradine, has offered the novel and unique opportunity to directly and exclusively interfere with HR and, thus, to validate the presence of a causal relationship between HR and prognosis. The BEAUTIFUL trial has recently confirmed that HR is a powerful negative prognostic predictor in patients with coronary artery disease and left ventricular systolic dysfunction. Particularly, subjects with a resting HR >70 b/min showed an increased risk of major adverse cardiovascular events. In these patients, HR reduction with ivabradine was associated with a reduction in major cardiac ischemic events, though not mortality. Further data will become available with the SHIFT trial in which patients with heart failure and HR > or =70 b/min are included and reduction in cardiovascular mortality and heart failure hospitalizations is the primary endpoint.


Correction of beam errors in high power laser diode bars and stacks.
The beam errors of an 11 bar laser diode stack fitted with fast-axis collimator lenses have been corrected by a single refractive plate, produced by laser cutting and polishing. The so-called smile effect is virtually eliminated and collimator aberration greatly reduced, improving the fast-axis beam quality of each bar by a factor of up to 5. The single corrector plate for the whole stack ensures that the radiation from all the laser emitters is parallel to a common axis. Beam-pointing errors of the bars have been reduced to below 0.7 mrad.


Long-term land application of biosolids-a case study.
Impact of long-term land application of biosolids on groundwater and soil quality of an application site, which had been operated for 8-15 years, was evaluated in this study. During and after the biosolids application, biosolids-amended soil, groundwater, and background soil samples were collected mainly for pathogen, nitrogen, phosphorus, and heavy metal analyses. Soil test data showed that there was no heavy metal accumulation in the biosolids-amended soil even after 10 years of biosolids application. Similar results were also observed from the groundwater samples in which the heavy metal concentrations in all groundwater samples were well below the maximum contamination levels of the drinking water standards. In addition, bacteriological levels of the soil and groundwater samples were close to the background level and below the permissible limits, respectively, thereby showing no pathogen contamination. However, nitrate-nitrogen contamination of the groundwater was occasionally observed probably due to an excess loading of the biosolids in the past. This problem can be alleviated by applying biosolids at agronomic rates so that no excess nitrogen is available for leaching down to the groundwater.


Respiratory Selenite Reductase from Bacillus selenitireducens Strain MLS10.
The putative respiratory selenite [Se(IV)] reductase (Srr) from Bacillus selenitireducens MLS10 has been identified through a polyphasic approach involving genomics, proteomics, and enzymology. Nondenaturing gel assays were used to identify Srr in cell fractions, and the active band was shown to contain a single protein of 80 kDa. The protein was identified through liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a homolog of the catalytic subunit of polysulfide reductase (PsrA). It was found to be encoded as part of an operon that contains six genes that we designated srrE, srrA, srrB, srrC, srrD, and srrF SrrA is the catalytic subunit (80 kDa), with a twin-arginine translocation (TAT) leader sequence indicative of a periplasmic protein and one putative 4Fe-4S binding site. SrrB is a small subunit (17 kDa) with four putative 4Fe-4S binding sites, SrrC (43 kDa) is an anchoring subunit, and SrrD (24 kDa) is a chaperon protein. Both SrrE (38 kDa) and SrrF (45 kDa) were annotated as rhodanese domain-containing proteins. Phylogenetic analysis revealed that SrrA belonged to the PsrA/PhsA clade but that it did not define a distinct subgroup, based on the putative homologs that were subsequently identified from other known selenite-respiring bacteria (e.g., Desulfurispirillum indicum and Pyrobaculum aerophilum). The enzyme appeared to be specific for Se(IV), showing no activity with selenate, arsenate, or thiosulfate, with a Km of 145 ± 53 μM, a Vmax of 23 ± 2.5 μM min-1, and a kcat of 23 ± 2.68 s-1 These results further our understanding of the mechanisms of selenium biotransformation and its biogeochemical cycle.IMPORTANCE Selenium is an essential element for life, with Se(IV) reduction a key step in its biogeochemical cycle. This report identifies for the first time a dissimilatory Se(IV) reductase, Srr, from a known selenite-respiring bacterium, the haloalkalophilic Bacillus selenitireducens strain MLS10. The work extends the versatility of the complex iron-sulfur molybdoenzyme (CISM) superfamily in electron transfer involving chalcogen substrates with different redox potentials. Further, it underscores the importance of biochemical and enzymological approaches in establishing the functionality of these enzymes.


Antimicrobial Resistance in Acinetobacter spp. and Pseudomonas spp.
The nonfermenting bacteria belonging to Acinetobacter spp. and Pseudomonas spp. are capable of colonizing both humans and animals and can also be opportunistic pathogens. More specifically, the species Acinetobacter baumannii and Pseudomonas aeruginosa have been recurrently reported as multidrug-resistant and even pandrug-resistant in clinical isolates. Both species were categorized among the ESKAPE pathogens, ESKAPE standing for Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter species. These six pathogens are the major cause of nosocomial infections in the United States and are a threat all over the world because of their capacity to become increasingly resistant to all available antibiotics. A. baumannii and P. aeruginosa are both intrinsically resistant to many antibiotics due to complementary mechanisms, the main ones being the low permeability of their outer membrane, the production of the AmpC beta-lactamase, and the production of several efflux systems belonging to the resistance-nodulation-cell division family. In addition, they are both capable of acquiring multiple resistance determinants, such as beta-lactamases or carbapenemases. Even if such enzymes have rarely been identified in bacteria of animal origin, they may sooner or later spread to this reservoir. The goal of this article is to give an overview of the resistance phenotypes described in these pathogens and to provide a comprehensive analysis of all data that have been reported on Acinetobacter spp. and Pseudomonas spp. from animal hosts.


Retinal Photoreceptor Protection in an AMD-Related Mouse Model by Selective Sigma-1 or Sigma-2 Receptor Modulation.
The structurally and genetically distinct sigma-1 receptor (S1R) and sigma-2 receptor (S2R) comprise a unique class of drug binding sites. Their alleles are associated with human diseases involving neuronal systems, such as age-related macular degeneration (AMD) characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. Previous studies have suggested neuroprotective benefits for the brain and retina from pharmacological modulation of S1R and/or S2R. However, the effect of such modulation on AMD pathology remains underexplored. Here, we evaluated S1R- or S2R-selective modulation in an AMD-related model of Abca4-/-Rdh8-/- mice with a disrupted visual cycle that predisposes RPE and photoreceptors to illumination-induced damage. For S1R modulation, we used (+)-pentazocine, which is a high-affinity S1R-selective drug. For S2R modulation, we chose CM398, a high-affinity and highly S2R-selective ligand with drug-like properties. Abca4-/-Rdh8-/- mice received a single i.p. injection of (+)-pentazocine or CM398 or vehicle 30 min before illumination. Pretreatment with (+)-pentazocine improved electroretinogram a- and b-waves compared to that with vehicle. Consistently, in another AMD-related mouse model induced by tail-vein injected NaIO3, S1R genetic ablation aggravated photoreceptor loss. In Abca4-/-Rdh8-/- mice, pretreatment with CM398 appeared to partially avert illumination-induced photoreceptor loss and autofluorescent granule formation that signals RPE damage, as revealed by optical coherence tomography. Thus, this study using AMD-related models provides evidence of photoreceptor protection afforded by selective modulation of S1R or S2R.


Artifacts, anatomical and physiological variants, and unrelated diseases that might cause false-positive whole-body 131-I scans in patients with thyroid cancer.
The whole body 131-I scan remains an important component in the postoperative treatment of patients with well-differentiated thyroid cancer. Because normal thyroid tissue remnants and residual or metastatic foci of well-differentiated thyroid cancer have the unique ability to concentrate, organify, and store 131-I, the whole body scan provides a depiction of those tissues that can be ablated with therapeutic doses of 131-I. Over time, it has become obvious that the whole body scan may also reveal foci of 131-i uptake owing to a wide variety of other causes. We provide a detailed pathophysiological classification of the artifacts, anatomic and physiological variants, and nonthyroidal diseases that may give rise to false-positive whole body scans in postoperative patients with thyroid cancer. These include ectopic foci of normal thyroid tissue; nonthyroidal physiological sites (eg, choroid plexus, salivary glands, gastric mucosa, urinary tract); contamination by physiological sections; ectopic gastric mucosa; other gastrointestinal abnormalities; urinary tract abnormalities; mammary abnormalities; serous cavities and cysts; inflammation and infection; nonthyroidal neoplasms; and currently unexplained causes. This article also provides a detailed review of the widely scattered English language literature in which these phenomena were originally described.


The use of natural products in colorectal cancer drug discovery.
Natural products (NPs) are evolutionarily designed and contain more complex and challenging structures than synthetic compounds. Since the 1980s, the pharmaceutical industry has gradually shifted to a strategy of developing targeted agents by screening libraries of synthetic compounds. However, NPs have recently received renewed focus as a rich repository for drug discovery. Irinotecan was developed as a derivative of camptothecin and was applied in standard regimens for metastatic colorectal cancer (CRC) worldwide. Additionally, polysaccharide K is approved for CRC in Japan and Taiwan in combination with cytotoxic agents. However, after the approval of irinotecan in 1996, no anti-cancer agents derived from NPs have been approved for CRC. This review discusses NPs that are currently under investigation for the treatment of CRC. In addition, other NPs derived as purified ingredients and crude extracts are listed and also discussed. The use of NPs for the discovery of anti-cancer agents has not been fully investigated. New technologies that are currently applied for synthetic compounds may be utilized for anti-cancer drug discovery including NPs for CRC.


Synthesis, characterization and catalytic epoxidation properties of lanthanide-stabilized peroxoisopolytungstates.
A series of new lanthanide-containing peroxoisopolyoxotungstates, K6Na4[H32{Ln4(WO4)(H2O)16[W7O22(O2)2]4}3]·105H2O [Ln = CeIII (1), NdIII (2), SmIII (3), TbIII (4), ErIII (5)], have been successfully synthesized and structurally characterized. All polyanions [Ln(WO4)(H2O)16{W7O22(O2)2}4]14- are isostructural and consist of a central [Ln(WO4)(H2O)16]10+ cluster surrounded by four peripheral [W7O22(O2)2]6- units. They could act as efficient recyclable catalysts for the epoxidation of various alkenes including different cycloalkenes, styrene derivatives, internal and long-chain alkenes. Under optimal conditions, catalyst 2 displays the best catalytic activity for the oxidation of cyclooctene with high cyclooctene conversion (98.3%) and excellent selectivity (up to 99%) and could be reused for three cycles with a negligible decrease in reactivity.


Human INT6 interacts with MCM7 and regulates its stability during S phase of the cell cycle.
The mouse int6 gene is a frequent integration site of the mouse mammary tumor virus and INT6 silencing by RNA interference in HeLa cells causes an increased number of cells in the G2/M phases of the cell cycle, along with mitotic defects. In this report, we investigated the functional significance of the interaction between INT6 and MCM7, which was observed in a two-hybrid screen performed with INT6 as bait. It was found that proteasome inhibition strengthens interaction between both proteins and that INT6 stabilizes MCM7. Removal of MCM7 from chromatin as replication proceeds was accelerated in INT6-silenced cells and reduced amounts of protein were transiently observed, followed by a correction resulting from stimulation of mcm7 gene expression. Synchronized cells depleted for either INT6 or MCM7 display a reduction in thymidine incorporation and a reinforced association of RPA and claspin with chromatin. These data show that INT6 stabilizes chromatin-bound MCM7 and that alteration of this effect is associated with replication deficiency.


Ginger (Zingiber officinale) Root Extract During Pregnancy: A Clinical Feasibility Study.
There is almost no experience with concentrated ginger extracts during pregnancy. The purpose of this trial was to include 50 pregnant women in a clinical feasibility study with EXT.GR10, a 10 × concentrated ethanolic extract of ginger root. The primary objective was to detect complications in the mother during pregnancy and malformations or complications in the newborn at delivery. The secondary purpose was to evaluate the satisfaction of the patients. In total, 51 pregnant women were included in this observational study. They could freely use ginger tablets with a maximum of 2 tablets of 50 mg EXT.GR10 a day in case of gastrointestinal discomfort. Tablets were taken by 44 patients. Stillbirth, prematurity, hypertension, and gestational diabetes occurred. There were no serious complications at birth. In the newborn, 4 cases of dysplasia of the hip were seen and 2 minor malformations. There was no relation between events affecting mother and child and the number of EXT.GR10 tablets taken. About ⅔ of patients appreciated the effects of ginger. This is the first clinical study with the EXT.GR10 extract. Based on this feasibility study, a follow-up clinical trial is planned with a fixed minimum of exposure to EXT.GR10 during the first trimester of pregnancy.


Cep57 and Cep57L1 maintain centriole engagement in interphase to ensure centriole duplication cycle.
Centrioles duplicate in interphase only once per cell cycle. Newly formed centrioles remain associated with their mother centrioles. The two centrioles disengage at the end of mitosis, which licenses centriole duplication in the next cell cycle. Therefore, timely centriole disengagement is critical for the proper centriole duplication cycle. However, the mechanisms underlying centriole engagement during interphase are poorly understood. Here, we show that Cep57 and Cep57L1 cooperatively maintain centriole engagement during interphase. Codepletion of Cep57 and Cep57L1 induces precocious centriole disengagement in interphase without compromising cell cycle progression. The disengaged daughter centrioles convert into centrosomes during interphase in a Plk1-dependent manner. Furthermore, the centrioles reduplicate and the centriole number increases, which results in chromosome segregation errors. Overall, these findings demonstrate that the maintenance of centriole engagement by Cep57 and Cep57L1 during interphase is crucial for the tight control of centriole copy number and thus for proper chromosome segregation.


Predicting Vaccination Intention against COVID-19 Using Theory of Planned Behavior: A Systematic Review and Meta-Analysis.
This study systematically analyzed the literature using the theory of planned behavior (TPB) as a theoretical framework to examine the influence of its constructs on vaccination intention against COVID-19. Quantitative studies were searched in PubMed, CINAHL, Web of Science, and Google Scholar following the PRISMA guidelines. The average rate of COVID-19 vaccination intention was 73.19%, ranging from 31% to 88.86%. Attitude had the strongest association with vaccination intention (r+ = 0.487, 95% CI: 0.368-0.590), followed by subjective norms (r+ = 0.409, 95% CI: 0.300-0.507), and perceived behavioral control (r+ = 0.286, 95% CI: 0.198-0.369). Subgroup analyses showed that the pooled effect sizes of TPB constructs on vaccination intention varied across geographic regions and study populations. Attitude had large effect sizes in Asia, Europe, and Oceania, especially among the adult general population, parents, and patients. Subjective norms had large effect sizes in Asia and Oceania, especially among parents and patients. Perceived behavioral control was the most dominant predictor of vaccination acceptance in Africa among patients. These findings suggest that TPB provides a useful framework for predicting intention to receive a COVID-19 vaccine. Hence, public awareness and educational programs aimed at promoting COVID-19 vaccination intention should consider using TPB as a framework to achieve the goal.


Hepatic metastasis in gestational trophoblastic neoplasia: patient characteristics, prognostic factors, and outcomes.
To identify patient characteristics, determine prognostic factors, and evaluate outcomes for women with hepatic metastases in gestational trophoblastic neoplasia (GTN). Seventeen GTN patients with hepatic metastases were treated at our institution between 1962 and 2010. Demographic data, disease characteristics, and survival were all analyzed retrospectively. Fisher's exact test was used to determine significance. The median age was 29 years (range, 16-48), and the antecedent pregnancy was nonmolar in 12 patients (75%) and a hydatidiform mole in 4 patients (25%). Fifteen patients (88%) had metastatic disease outside the liver, including lung (13), brain (5), and other intraabdominal organs (8). Median FIGO score was 14 (range, 12-19). Chemotherapy consisted of single-agent methotrexate or actinomycin D in 2 patients; methotrexate, actinomycin D, cyclophosphamide (MAC) in 4 patients; and etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMACO) in 11 patients. Complete response rate to chemotherapy was 82% for EMA-CO versus 17% for other types of chemotherapy (p = 0.035). Overall survival was 41% (7/17). Survival of patients with GTN and hepatic metastases increased from 17% (1/6) to 55% (6/11) after 1986 when EMA-CO chemotherapy was introduced. Survival was significantly decreased for patients with concomitant intraabdominal or brain metastases (11% vs. 75%, p = 0.015).


Tuberculin test.
Although tuberculin test is widely used for detection of tuberculous infection among children, there is no clear understanding about its performance and interpretation. This article has been written with the purpose of elucidating the performance and interpretation of standard tuberculin test, based on the experiences gained at the National Tuberculosis Institute, Bangalore and other centres. The standard tuberculin test involves intradermal injection of '1TU PPD RT23 with Tween 80' on the mid-volar aspect of forearm and measurement of the maximum transverse diameter of induration after 3 days. Larger the size of induration, higher is the probability of it being due to tuberculous infection. The majority of reactions with induration size of 15 mm and above are attributable to infection with tubercle bacilli, irrespective of BCG-vaccination status. While indurations of less than 5 mm indicate absence of any kind of tuberculin sensitivity, the majority of indurations in 5-9 mm range are usually of non-tuberculous nature. An induration of 10-14 mm requires more careful interpretation. It is more likely to be attributable to infection with tubercle bacilli in case of history of contact with smear positive case or among children with clinical findings of tuberculosis. However, the size of induration in an infected child may be diminished in the presence of immuno-suppressive conditions. One should also consider the purpose of the test while interpreting the test results.


Choice of a Suitable Dosimeter for Photon Percentage Depth Dose Measurements in Flattening Filter-Free Beams.
The International Atomic Energy Agency Technical Reports Series-398 code of practice for dosimetry recommends measuring photon percentage depth dose (PDD) curves with parallel-plate chambers. This code of practice was published before flattening filter-free (FFF) beams were widely used in clinical linear accelerators. The choice of detector for PDD measurements needs to be reassessed for FFF beams given the physical differences between FFF beams and flattened ones. The present study compares PDD curves for FFF beams of nominal energies 6 MV, 6 FFF, 10 MV, and 10 FFF from a Varian TrueBeam linear accelerator (Varian Medical Systems, Palo Alto, USA) acquired with Scanditronix photon diodes, two scanning type chambers (both PTW 31010 Semiflex), two small volume chambers (Wellhofer CC04 and PTW 31016 PinPoint 3D), PTW 34001 Roos, Scanditronix Roos, and NACP 02 parallel-plate chambers. Results show that parallel-plate ion chambers can be used for photon PDD measurements, although for better accuracy, recombination effects should be taken into account.


17β-Estradiol regulates cyclin A1 and cyclin B1 gene expression in adult rat seminiferous tubules.
Spermatogenesis, which is the fundamental mechanism allowing male gamete production, is controlled by several factors, and among them, estrogens are likely concerned. In order to enlighten the potential role of estrogen in rat spermatogenesis, seminiferous tubules (ST) from two groups of seminiferous epithelium stages (II-VIII and IX-I) were treated with either 17β-estradiol (E(2)) agonists or antagonists for estrogen receptors (ESRs). In this study, we show that cyclin A1 and cyclin B1 gene expression is controlled by E(2) at a concentration of 10(-9) M only in stages IX-I. This effect is mimicked by a treatment with the G-protein coupled estrogen receptor (GPER) agonist G1 and is abolished by treatment with the ESR antagonist ICI 182 780. Moreover, using letrozole, a drug that blocks estrogen synthesis, we demonstrate that these genes are under the control of E(2) within rat ST. Thus, germ cell differentiation may be regulated by E(2) which acts through ESRs and GPER, expressed in adult rat ST.


Nationwide Study on the Risk of Abdominal Aortic Aneurysms in Patients With Psoriasis.
Abdominal aortic aneurysm (AAA) is a complex multifactorial disease associated with a high morbidity and mortality. Increased inflammation including T-helper 17 cell-mediated effects has been implicated in AAA pathogenesis. Psoriasis is considered to be a T-helper 17-driven chronic inflammatory disease and in view of potentially overlapping inflammatory mechanisms, we investigated the risk of AAA in patients with psoriasis in a nationwide cohort. The study comprised all Danish residents aged ≥18 years followed up from January 1, 1997, until diagnosis of AAA, December 31, 2011, migration or death. Information on comorbidity, concomitant medication, and socioeconomic status was identified by individual-level linkage of administrative registers. Incidence rates for AAA were calculated and incidence rate ratios adjusted for age, sex, comorbidity, medications, socioeconomic status, and smoking were estimated in Poisson regression models. A total of 5 495 203 subjects were eligible for analysis. During the study period, we identified 59 423 patients with mild psoriasis and 11 566 patients with severe psoriasis. The overall incidence rates of AAA were 3.72, 7.30, and 9.87 per 10 000 person-years for the reference population (23 696 cases), mild psoriasis (240 cases), and severe psoriasis (50 cases), respectively. The corresponding adjusted incidence rate ratios for AAA were increased in patients with psoriasis with incidence rate ratios of 1.20 (95% confidence interval, 1.03-1.39) and 1.67 (confidence interval, 1.21-2.32) for subjects with mild and severe disease, respectively. In a nationwide cohort, psoriasis was associated with a disease severity-dependent increased risk of AAA. The mechanisms and consequences of this novel finding require further investigation.


Vaginal antibody of patients with trichomoniasis is to a prominent surface immunogen of Trichomonas vaginalis.
Twenty vaginal washes (VWs) and ten vaginal mucus (VM) samples from patients with trichomoniasis were examined for the presence of antibody to surface protein immunogens of Trichomonas vaginalis. Fourteen of 20 VWs (70%) and 8 of 10 VM (80%) had immunoglobulin G (IgG) antibody (Ab) that reacted in an immunoprecipitation (IP) assay with one iodinated Trichomonas vaginalis surface protein immunogen with a relative molecular mass of 230,000 daltons (230-kDa) (P230). No similar IP of any iodinated protein was observed when detergent extract was first depleted of P230 with monoclonal antibody (MAb), indicating a highly specific VW IgG response of patients to P230. VWs were also obtained from 10 patients from one to four weeks after treatment. These VWs had the same, or in one case a greater, level of IgG to P230. Under no circumstances was Ab to P230 or any other trichomonad protein detected in VWs or VM from normal, uninfected women. Flow cytofluorometry with VW Ab yielded heterogeneous fluorescent and non-fluorescent populations of trichomonads, reaffirming the restricted Ab response to one or a few epitopes on P230 in the vagina of patients. Under identical conditions, the MAb gave totally fluorescent parasite populations of some isolates, and the MAb again demonstrated variable epitope accessibility to Ab binding (Infect Immun 1987;55:1037). Finally, the MAb or VW Ab was never cytolytic for immunoreactive (fluorescent) parasites, even in the presence of complement. This study identifies the most important trichomonad surface immunogen on the basis of the vaginal Ab response, and data underscore the significance of immune evasion strategies of this sexually transmitted disease agent.


Cytoplasmic effects of cortisol in liver.
1. The time-course of the induction by cortisol of tryptophan pyrrolase in mouse liver was established. 2. The kinetics of labelling of mouse liver polyribosomes and the distribution of radioactivity in the various sizes of polyribosomes were investigated. It is concluded that the major part of the messenger RNA is monocistronic. 3. Cortisol administered to adrenalectomized mice stimulates in parallel the ability of ribosomes and polyribosomes, both free and bound, to incorporate amino acids into protein. 4. This stimulation does not appear to affect in a selective manner particular regions of the gradients of polyribosomes. 5. Administration of cortisol enhances the ability of the denser fraction of the rough microsomes to incorporate labelled amino acids. Adrenalectomy has minor effects on the pool sizes and specific radioactivities of liver amino acids which are counteracted by the hormone. However, these appear insufficient to influence the changes observed. 6. Adrenalectomy causes an increase in the percentage of ribosomes existing as polyribosomes and a fall in the proportion bound to the membrane of the endoplasmic reticulum. After treatment of these animals with cortisol there is a marked increase in the proportion of bound ribosomes. 7. The influence of cortisol on the membranous components of liver cytoplasm is discussed.


Highly Efficient Light Helicity Detection of Enantiomers by Chiral Metal-Organic Framework Thin Films.
The potential of chiral metal-organic frameworks (MOFs) for circularly polarized (CP) optics has been largely unexplored. Herein, we have successfully deposited monolithic and highly oriented chiral MOF thin films prepared by a layer-by-layer method (referred to as surface-coordinated MOF thin films, SURMOF) to fabricate CP photodetection devices and distinguish enantiomers. The helicity-sensitive absorption induced by a pair of enantiopure oriented SURMOF was found to be excellent, with an anisotropy factor reaching 0.41. Moreover, the chiral SURMOFs exhibited a pronounced difference in the uptake of the l- and d-tryptophan enantiomers. To demonstrate the potential of these novel MOF thin films for chirality analysis, we fabricated a portable sensor device that allows for chiral recognition by monitoring the photocurrent signals. Our findings not only introduce a new concept of using chiral building blocks for realizing direct CP photodetectors but also provide a blueprint for novel devices in chiral optics.


[Human exposure to trihalomethanes in drinking water].
Halogenated hydrocarbon compounds, some of them recognized as carcinogenic to different animal species can be found in drinking water. Chloroform, bromodichloromethane, dibromochloromethane and bromoform are the most important trihalomethanes found in potable water. They are produced in natural waters during chlorinated desinfection by the halogenation of precursors, specially humic and fulvic compounds. The review, in the MEDLINE covers the period from 1974 to 1998, presents the general aspects of the formation of trihalomethanes, sources of human exposure and their toxicological meaning for exposed organisms: toxicokinetic disposition and spectrum of toxic effects (carcinogenic, mutagenic and teratogenic).


Dosimetric principles for extrapolating results of rat inhalation studies to humans, using an inhaled Ni compound as an example.
Dose-effect relationships of inhaled substances are complicated by the interrelationship between inhaled dose, deposited dose, and retained dose. Deposited and retained doses are most important for evaluating dose-effect relations; however, inhaled dose and exposure concentration that are not representative of the actual dose to target sites are widely used for this purpose. For extrapolating results of animal inhalation studies to humans, several factors have to be considered for calculating a human equivalent dose to the respiratory tract and for estimating a human equivalent exposure concentration. Among these factors are separate deposition in nasopharyngeal, tracheobronchial, and alveolar regions, both total regional deposition and deposited dose per unit surface area. Predictive particle deposition models for the respiratory tract can be used for calculating these. The retained dose is another factor that takes into account respiratory tract retention and determines the long-term dose to the respiratory tract. A rat inhalation study using Ni3S2 exposure (concentration, 970 micrograms m-3; duration, 78 wk; exposure, 6 h d-1, 5 d wk-1) resulted in bronchogenic and alveologenic tumors. Extrapolation modeling of rat data was performed based on dose factors discussed above, and assuming different conditions of pulmonary retention for Ni3S2 with half-times of 36 d for rats and 103 d for humans. Model calculations showed that deposited surface area dose was greater for the tracheobronchial than for the pulmonary region in both rat and man. The retained dose per gram of lung was greater in rat than in man under resting conditions. An equivalent exposure concentration would be lower in humans than in the rat if it is based on the retained dose expressed per square centimeter of alveolar surface area. However, inhaled equivalent concentration in man can be considerably higher when the tracheobronchial surface area dose is considered. The most sensitive region of the respiratory tract--for example, with regard to tumor induction--should be selected for estimating human equivalent exposure.


Spatial view cells in the primate hippocampus.
Hippocampal function was analysed by making recordings in rhesus monkeys actively walking in the laboratory. In a sample of 352 cells recorded in the hippocampus and parahippocampal cortex, a population of 'spatial view' cells was found to respond when the monkey looked at a part of the environment. The responses of these hippocampal neurons (i) occur to a view of space 'out there', not to the place where the monkey is, (ii) depend on where the monkey is looking, as shown by measuring eye position, (iii) do not encode head direction, and (iv) provide a spatial representation that is allocentric, i.e. in world coordinates. This representation of space 'out there' would be an appropriate part of a primate memory system involved in memories of where in an environment an object was seen, and more generally in the memory of particular events or episodes for which a spatial component normally provides part of the context.


Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in AIDS patients with acute kidney injury.
The objective of the present study was to determine the prevalence of electrolyte disturbances in AIDS patients developing acute kidney injury in the hospital setting, as well as to determine whether such disturbances constitute a risk factor for nephrotoxic and ischemic injury. A prospective, observational cohort study was carried out. Hospitalized AIDS patients were evaluated for age; gender; coinfection with hepatitis; diabetes mellitus; hypertension; time since HIV seroconversion; CD4 count; HIV viral load; proteinuria; serum levels of creatinine, urea, sodium, potassium and magnesium; antiretroviral use; nephrotoxic drug use; sepsis; intensive care unit (ICU) admission, and the need for dialysis. Each of these characteristics was correlated with the development of acute kidney injury, with recovery of renal function and with survival. Fifty-four patients developed acute kidney injury: 72% were males, 59% had been HIV-infected for >5 years, 72% had CD4 counts <200 cells/mm(3), 87% developed electrolyte disturbances, 33% recovered renal function, and 56% survived. ICU admission, dialysis, sepsis and hypomagnesemia were all significantly associated with nonrecovery of renal function and with mortality. Nonrecovery of renal function was significantly associated with hypomagnesemia, as was mortality in the multivariate analysis. The risks for nonrecovery of renal function and for death were 6.94 and 6.92 times greater, respectively, for patients with hypomagnesemia. In hospitalized AIDS patients, hypomagnesemia is a risk factor for nonrecovery of renal function and for in-hospital mortality. To determine whether hypomagnesemia is a determinant or simply a marker of critical illness, further studies involving magnesium supplementation in AIDS patients are warranted.


Racial disparities in infant mortality: a quality of care perspective.
Black infants in the United States are more than twice as likely to die as White infants in the first year of life. Reducing the existing racial disparity in infant mortality rates is a major health policy focus. Despite decades of research aimed at reducing preterm births, our efforts have been largely unsuccessful. Much greater success has been achieved in reducing the morbidity and mortality of premature infants, largely through improvements in obstetrical and neonatal care. However, it is an open question whether such improvements have reduced racial disparities in infant mortality. In this article, we recommend a new framework for addressing infant mortality disparities. We suggest that a quality of care problem may partially underlie racial disparities in infant mortality rates.


Anomalous heat capacities of supercooled water and heavy water.
Emulsification makes it possible to supercool water to the homogeneous nucleation temperature. Accordingly, the heat capacities of water and deuterium oxide have been determined from the respective equilibrium melting points to -38 degrees and to -34 degrees C, respectively. Two methods, drift calorimetry and differential scanning calorimetry, have been used. Both methods reveal a striking rise in the constant-pressure heat capacity below -20 degrees C. This indication of an apparently cooperative behavior should serve to test current theories of water, most notably perhaps, the pair potential model of Ben-Naim and Stillinger. Some implications of possible meteorological significance are mentioned.


Vaginal evisceration related to genital prolapse in premenopausal woman.
Vaginal evisceration is a rare problem, usually related to a previous hysterectomy. We report a case of spontaneous rupture of the cul-de-sac in a premenopausal woman under treatment with glucocorticoids to treat Systemic Lupus Erythematosus (SLE), with uterine prolapse that occurred during evacuation. Main findings-Case Report: A 40-year-old woman with SLE, using glucocorticoids, with uterine prolapse grade 4 (POP-Q), awaiting surgery presented at the emergency room with vaginal bleeding after Valsalva during defection. Uterine prolapse associated with vaginal evisceration was identified. Under vaginal examination, we confirmed the bowel viability and performed a vaginal hysterectomy and sacrospinous fixation. Case hypothesis: This case draws attention to the extreme risk of untreated uterine prolapse, as well as the importance of multidisciplinary care of patients with vaginal prolapse and chronic diseases.


Impact of High-Deductible Health Plans on Medication Use Among Individuals With Bipolar Disorder.
High-deductible health plans (HDHPs) require substantial out-of-pocket spending for most services, although medications may be subject to traditional copayment arrangements. This study examined effects of HDHPs on medication out-of-pocket spending and use and quality of care among individuals with bipolar disorder. This quasi-experimental study used claims data (2003-2014) for a national sample of 3,532 members with bipolar disorder, ages 12-64, continuously enrolled for 1 year in a low-deductible plan (≤$500) and then for 1 year in an HDHP (≥$1,000) after an employer-mandated switch. HDHP members were matched to 18,923 contemporaneous individuals in low-deductible plans (control group). Outcome measures were out-of-pocket spending and use of bipolar disorder medications, psychotropics for other disorders, and all other medications and appropriate laboratory monitoring for psychotropics. Relative to the control group, annual out-of-pocket spending per person for bipolar disorder medications increased 20.8% among HDHP members (95% confidence interval [CI]=14.9%-26.7%), and the absolute increase was $36 (95% CI=$25.9-$45.2). Specifically, out-of-pocket spending increased for antipsychotics (27.1%; 95% CI=17.4%-36.7%) and anticonvulsants (19.2%; 95% CI=11.9%-26.6%) but remained stable for lithium (-3.7%; 95% CI=-12.2% to 4.8%). No statistically significant changes were detected in use of bipolar disorder medications, other psychotropics, or all other medications or in appropriate laboratory monitoring for bipolar disorder medications. HDHP members with bipolar disorder experienced a moderate increase in out-of-pocket spending for medications but preserved bipolar disorder medication use. Findings may reflect individuals' perceptions of the importance of these medications for their functioning and well-being.


An ethnographic study of psychiatric nursing.
There is a well documented continuing anomaly between what is expected of a psychiatric nurse and observations of practice. This paper presents an ethnographic study carried out in three acute psychiatric in-patient units over one year. Methods used were participant observation and semistructured interviews of 15 trained nurses. Three themes were isolated during and following data analysis: the difficulty of working closely with mentally disturbed individuals; maintaining distance and congruent care. There was a notable dichotomy, that of wanting to work with the patients but constantly feeling that what they intuitively wanted to do was not right.


Magnetic-field-induced nematic-columnar phase transition in aqueous suspensions of goethite (alpha-FeOOH) nanorods.
Colloidal aqueous suspensions of goethite lath-shaped nanorods form nematic and isotropic phases. We show that they also display a 2D rectangular (c2mm) columnar phase at volume fractions phi larger than 15%. Interestingly, the nematic-columnar first-order transition can also be triggered by applying to the nematic phase a magnetic field of intensity decreasing with phi (1 T at 8.5%; 0.5 T at 12%). Single domains of the columnar phase were thus produced and their structure investigated by synchrotron x-ray scattering. This magnetic-field-induced transition is fully reversible and reproducible.


Four-laser airborne infrared spectrometer for atmospheric trace gas measurements.
We describe the four-laser airborne infrared (FLAIR) instrument, a tunable diode laser absorption spectrometer designed for simultaneous high-sensitivity in situ measurements of four atmospheric trace gases in the troposphere. The FLAIR spectrometer was employed during the large-scale airborne research campaign on tropospheric ozone (TROPOZ II) in 1991 and was used to measure CO, H(2) O(2), HCHO, and NO(2) in the free troposphere where detection limits below 100 parts in 10(12) by volume were achieved.


Mutations in SDCCAG8/NPHP10 Cause Bardet-Biedl Syndrome and Are Associated with Penetrant Renal Disease and Absent Polydactyly.
The ciliopathies are an expanding group of disorders caused by mutations in genes implicated in the biogenesis and function of primary cilia. Bardet-Biedl syndrome (BBS) is a model ciliopathy characterized by progressive retinal degeneration, obesity, polydactyly, cognitive impairment, kidney anomalies and hypogonadism. Mutations in SDCCAG8(NPHP10) were described recently in patients with nephronophthisis and retinal degeneration (Senior-Loken syndrome; SLS). Given the phenotypic and genetic overlap between known ciliopathy genes, we hypothesized that mutations in SDCCAG8 might also contribute alleles to more severe, multisystemic ciliopathies. We performed genetic and phenotypic analyses of 2 independent BBS cohorts. Subsequent to mutation screening, we made a detailed phenotypic analysis of 5 families mutated for SDCCAG8 (3 homozygous and 2 compound heterozygous mutations) and conducted statistical analyses across both cohorts to examine possible phenotype-genotype correlations with mutations at this locus. All patients with mutations in SDCCAG8 fulfilled the diagnostic criteria for BBS (retinal degeneration, obesity, cognitive defects, renal failure, hypogonadism). Interestingly, none of the patients with primary SDCCAG8 mutations had polydactyly, a frequent but not obligatory BBS feature. In contrast, the same patients displayed early-onset renal failure, obesity, as well as recurrent pulmonary and ENT infections. Comparison of the phenotypes of these families with our entire BBS cohort indicated that renal impairment and absent polydactyly correlated significantly with causal SDCCAG8 mutations. Thus, SDCCAG8 mutations are sufficient to cause BBS in 1-2% of our combined cohorts, and define this gene as the sixteenth BBS locus (BBS16). The absence of polydactyly and the concomitant, apparently fully penetrant association with early kidney failure represents the first significant genotype-phenotype correlation in BBS that potentially represents an indicator for phenotype-driven priority screening and informs specific patient management.


A survey on bloat in southern Australian beef production systems.
Frothy bloat, associated predominantly with grazing legume-based pastures, is considered the second most costly disease in beef cattle in southern Australia, costing $84.4 M annually. It frequently results in the sudden death of cattle. In response to concerns from cattle producers, an online survey was conducted in southern Australia in late 2020 to determine the impact of bloat, identify risk factors and determine the efficacy of current preventive measures. For 217 responses, over two-thirds (70%) of producers reported bloat occurring in the previous 12 months, with estimated morbidity and mortality rates of 3.7% and 5.0% respectively. Bloat was associated with clover or clover-dominant paddocks (79%) and was not associated with grass or grass-dominant pastures or low clover pastures (92%) nor grazing crops (27%). For bloat that occurred in the past 12 months, cattle were very commonly grazing on clover or clover-dominant paddocks (90%) and occasionally lucerne-dominated paddocks (7%). Two-thirds of producers reported having preventive measures in place when losses occurred. Bayesian Network analysis confirmed that grazing clover-based pastures for more than 7 days, yearling cattle and the months of July-September were the main risk factors for bloat occurrence, with pasture type (clover) being the most important. Conversely, no clear relationship between weather conditions and bloat occurrence was evident. This survey highlights the known risk of clover-based pastures for causing bloat in cattle, and that losses occur in many cases despite preventive measures being used. This suggests that current methods for preventing bloat in cattle are suboptimal.


Optogenetic Central Amygdala Stimulation Intensifies and Narrows Motivation for Cocaine.
Addiction is often characterized by intense motivation for a drug, which may be narrowly focused at the expense of other rewards. Here, we examined the role of amygdala-related circuitry in the amplification and narrowing of motivation focus for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2) stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala (BLA) of female rats with one particular nose-poke porthole option for earning cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned identical cocaine but without ChR2 stimulation. Consequently, CeA rats quickly came to pursue their CeA ChR2-paired cocaine option intensely and exclusively, elevating cocaine intake while ignoring their alternative cocaine alone option. By comparison, BLA ChR2 pairing failed to enhance cocaine motivation. CeA rats also emitted consummatory bites toward their laser-paired porthole, suggesting that higher incentive salience made that cue more attractive. A separate progressive ratio test of incentive motivation confirmed that CeA ChR2 amplified rats' motivation, raising their breakpoint effort price for cocaine by 10-fold. However, CeA ChR2 laser on its own lacked any reinforcement value: laser by itself was never self-stimulated, not even by the same rats in which it amplified motivation for cocaine. Conversely, CeA inhibition by muscimol/baclofen microinjections prevented acquisition of cocaine self-administration and laser preference, whereas CeA inhibition by optogenetic halorhodopsin suppressed cocaine intake, indicating that CeA circuitry is needed for ordinary cocaine motivation. We conclude that CeA ChR2 excitation paired with a cocaine option specifically focuses and amplifies motivation to produce intense pursuit and consumption focused on that single target.SIGNIFICANCE STATEMENT In addiction, intense incentive motivation often becomes narrowly focused on a particular drug of abuse. Here we show that pairing central nucleus of amygdala (CeA) optogenetic stimulation with one option for earning intravenous cocaine makes that option almost the exclusive focus of intense pursuit and consumption. CeA stimulation also elevated the effort cost rats were willing to pay for cocaine and made associated cues become intensely attractive. However, we also show that CeA laser had no reinforcing properties at all when given alone for the same rats. Therefore, CeA laser pairing makes its associated cocaine option and cues become powerfully attractive in a nearly addictive fashion.


Anaesthetic management of a patient with dilated cardiomyopathy for fracture femur surgery-a case report.
Dilated cardiomyopathy (DCM) is defined as impairment of the ventricular function of the myocardium. The management of a patient with dilated cardiomyopathy, who undergoes a non-cardiac surgery, is always a challenge for an anaesthesiologist, as this situation is associated with a high mortality rate. We are reporting the successful anaesthetic management of a patient with severe dilated cardiomyopathy for fractured femur surgical repair under graded epidural anaesthesia.


Identification of a cardiac specific protein transduction domain by in vivo biopanning using a M13 phage peptide display library in mice.
A peptide able to transduce cardiac tissue specifically, delivering cargoes to the heart, would be of significant therapeutic potential for delivery of small molecules, proteins and nucleic acids. In order to identify peptide(s) able to transduce heart tissue, biopanning was performed in cell culture and in vivo with a M13 phage peptide display library. A cardiomyoblast cell line, H9C2, was incubated with a M13 phage 12 amino acid peptide display library. Internalized phage was recovered, amplified and then subjected to a total of three rounds of in vivo biopanning where infectious phage was isolated from cardiac tissue following intravenous injection. After the third round, 60% of sequenced plaques carried the peptide sequence APWHLSSQYSRT, termed cardiac targeting peptide (CTP). We demonstrate that CTP was able to transduce cardiomyocytes functionally in culture in a concentration and cell-type dependent manner. Mice injected with CTP showed significant transduction of heart tissue with minimal uptake by lung and kidney capillaries, and no uptake in liver, skeletal muscle, spleen or brain. The level of heart transduction by CTP also was greater than with a cationic transduction domain. Biopanning using a peptide phage display library identified a peptide able to transduce heart tissue in vivo efficiently and specifically. CTP could be used to deliver therapeutic peptides, proteins and nucleic acid specifically to the heart.


Tardive dyskinesia.
Tardive dyskinesia (TD) is iatrogenic (drug-induced); hence the best strategy is prevention. Try to limit exposure to any dopamine receptor blocking agents (DRBAs) if possible. These agents may be unavoidable in some psychiatric conditions such as schizophrenia, but alternative therapies can be used in many situations, such as in the treatment of depression, anxiety, gastrointestinal conditions, and other neurologic conditions, including migraines and sleep disorders. When DRBAs are necessary, physicians should prescribe the smallest possible dose and try to taper and stop the drug at the earliest signs of TD. Abrupt cessation should be avoided, as this can worsen symptoms of TD. Always discuss and document the possibility of TD as an adverse effect when starting patients on DRBAs. If TD is mild and tolerable, the withdrawal of the offending agent is possible, and exposure to DRBAs was short, physicians should consider avoiding treatment and waiting for spontaneous recovery. When treatment is necessary, tetrabenazine (TBZ) is considered a potential first-line agent and is known to be one of the most effective drugs in treating TD, but it is expensive and adverse effects such as depression, akathisia and parkinsonism frequently occur. Therefore, second-line agents with better tolerability profiles are often tried first in practice. These include amantadine, benzodiazepines, beta-blockers, and levetiracetam. When using TBZ, adverse effects should be aggressively monitored. (Depression often can be managed with antidepressants, for instance). In patients with psychosis, withdrawal of the antipsychotic may not be possible. Switching to clozapine or quetiapine is one option to minimize TD. When these agents are contraindicated and the patient must continue using other atypical antipsychotic drugs, try to add dopamine-depleting agents such as TBZ or reserpine, but watch for the development of parkinsonism. When the symptoms are focal, such as tongue protrusion or blepharospasm, botulinum toxin injections can be very effective if spontaneous recovery does not occur. As a last resort, when disabling, life-threatening symptoms of TD persist despite all of the above-mentioned methods, some advocate resuming treatment with the DRBA to suppress symptoms of TD. This has the potential to worsen TD in the long run.


Protection against Helicobacter pylori and other bacterial infections by garlic.
Louis Pasteur was the first to describe the antibacterial effect of onion and garlic juices. Historically, garlic has been used worldwide to fight bacterial infections. Allium vegetables, particularly garlic (Allium sativum L.) exhibit a broad antibiotic spectrum against both gram-positive and gram-negative bacteria. Noteworthy results published include the following: 1) raw juice of garlic was found to be effective against many common pathogenic bacteria-intestinal bacteria, which are responsible for diarrhea in humans and animals; 2) garlic is effective even against those strains that have become resistant to antibiotics; 3) the combination of garlic with antibiotics leads to partial or total synergism; 4) complete lack of resistance has been observed repeatedly; 5) even toxin production by microorganisms is prevented by garlic. Helicobacter pylori (H. pylori) is a bacterium implicated in the etiology of stomach cancer and ulcers. The incidence of stomach cancer is lower in populations with a high intake of allium vegetables. We have demonstrated in vitro that H. pylori is susceptible to garlic extract at a fairly moderate concentration. Even some antibiotic-resistant H. pylori strains are susceptible to garlic. Clinical trials are necessary to explore the possibility of using garlic as a low-cost remedy for eradicating H. pylori.


Studies on the mechanism of fluid secretion by isolated salivary glands of Calliphora.
1. Potassium is the major cation in the secretion of the salivary glands of Calliphora and is necessary for full secretory rates. 2. Other ions (rubidium and sodium) can support secretion in the absence of potassium. 39. During stimulation with 5-HT a Nernst plot of the basal membrane potential has a slope of 53 mV for a tenfold change in external potassium concentration and the slope at rest deviates from this over the range I-20 mM external potassium. 4. Hyperpolarization of the basal membrane by 5-HT is abolished if the chloride in the bathing medium is replaced by isethionate. 5. The diuretic agent amiloride inhibits fluid secretion by a mechanism which may include a reduction in calcium entry in addition to its recognized effect on sodium permeability. 6. A model is proposed in which fluid secretion is driven by the active transport of potassium across the apical membrane with chloride following passively.


Selenite ameliorates the ATP hydrolysis of mitochondrial F1FO-ATPase by changing the redox state of thiol groups and impairs the ADP phosphorylation.
Selenite as an inorganic form of selenium can affect the redox state of mitochondria by modifying the thiol groups of cysteines. The F1FO-ATPase has been identified as a mitochondrial target of this compound. Indeed, the bifunctional mechanism of ATP turnover of F1FO-ATPase was differently modified by selenite. The activity of ATP hydrolysis was stimulated, whereas the ADP phosphorylation was inhibited. We ascertain that a possible new protein adduct identified as seleno-dithiol (-S-Se-S-) mercaptoethanol-sensitive caused the activation of F-ATPase activity and the oxidation of free -SH groups in mitochondria. Conversely, the inhibition of ATP synthesis by selenite might be irreversible. The kinetic analysis of the activation mechanism was an uncompetitive mixed type with respect to the ATP substrate. Selenite bound more selectively to the F1FO-ATPase loaded with the substrate by preferentially forming a tertiary (enzyme-ATP-selenite) complex. Otherwise, the selenite was a competitive mixed-type activator with respect to the Mg2+ cofactor. Thus, selenite more specifically bound to the free enzyme forming the complex enzyme-selenite. However, even if the selenite impaired the catalysis of F1FO-ATPase, the mitochondrial permeability transition pore phenomenon was unaffected. Therefore, the reversible energy transduction mechanism of F1FO-ATPase can be oppositely regulated by selenite.