Role of the mononuclear phagocyte system in the development of acquired immunodeficiency syndrome (AIDS).
This review describes current understanding of the role of cells of the mononuclear phagocyte system in the development of acquired immunodeficiency syndrome (AIDS). Monocyte-macrophage like cells have been shown to harbor human immunodeficiency virus type 1 (HIV-I) infection in both peripheral blood and bone marrow as well as in target organs such as brain, lungs, lymph nodes, and skin. Mononuclear phagocytes that have been infected by HIV-I do not undergo significant cytopathic changes, suggesting that they may be important viral reservoirs. These and related cells may also promote the slow, persistent nature of HIV-I infections by escaping host immunologic surveillance mechanisms. There is evidence that HIV-I infections in monocytes and premonocytes can initially be latent but progress to an active viral replication state upon differentiation and/or maturation. Functional abnormalities in the mononuclear phagocyte system following infection by HIV-I have also been described, and these may be partially responsible for the severe immunosuppression characteristic of AIDS and AIDS-related disorders. These defects may be mediated by quantitative and qualitative changes in the T-helper population. Although the role of mononuclear phagocytes as viral reservoirs and as mediators of immunosuppression is still largely speculative, increasing evidence suggests that these cells influence the course of HIV-I infections.


Primary malignant melanoma of the gastrointestinal tract: a case report and review of the literature.
Although most gastrointestinal melanomas are metastatic of origin, primary malignant melanomas of the gastrointestinal tract do exist. Over the last ten years, we encountered six patients with primary malignant melanoma of the mucosal lining of the gastrointestinal tract. The literature is reviewed, the pathophysiological aspects of these tumours are described and the surgical treatment is discussed.


Report of a Fatal Pediatric Case of Hemophagocytic Lymphohistiocytosis Associated with Pandemic Influenza A (H1N1) Infection in 2009.
An acute viral infection may lead to death, as seen in the recent novel 2009 influenza A (H1N1) virus pandemic that rapidly spread worldwide. Hemophagocytic lymphohistiocytosis (HLH) is a systemic disorder with high mortality rates and can be triggered by various etiological agents, including viral infections. H1N1-associated HLH is a very rare condition that may cause extremely severe complications leading to multiple organ failure (MOF) and death. We report an unusual case of a rapidly progressive and fatal H1N1 infection that was complicated with HLH and MOF in a previously healthy 8-year-old Asian female who initially presented with fever and abdominal pain. To enable early recognition and proper treatment, physicians should be aware of the possibility of this fatal complication, which may present with unusual initial symptoms.


Combined modality therapy in the treatment of gynecologic malignancies.
During the last several years, combined modality therapy has become increasingly important in the treatment of several malignancies. This trend holds true in the treatment of the gynecologic malignancies. In this review we examine the evolving role of combined modality therapy in the treatment of patients with cervical, vulvar, endometrial, and ovarian cancers. Definitive combined chemoradiation has become the new standard of care for patients with locally advanced cervical cancer. Combined chemoradiation provides for improvements in many clinical endpoints, including overall and disease-free survival. Chemoradiation has been used with some success in the treatment of patients with locally advanced vulvar carcinoma and has allowed some patients to avoid disfiguring surgery. Combined chemoradiation is being used in the treatment of patients with endometrial cancer who are found to be at high risk of recurrence after hysterectomy. In the setting of ovarian cancer, abdominopelvic radiation, either with or without chemotherapy, has shown some promise in the treatment of patients with minimal residual disease after resection. Combined modality therapy has played an increasingly important role in the treatment of gynecologic malignancies and its role continues to evolve and expand.


Species-dependent differences in ATP half-life of glucose deprived crystalline lens.
1. Significant differences were detected by 31P NMR spectroscopic techniques in the intrinsic rate of ATP hydrolysis by crystalline lenses from adult Macaca mulatta, Saimiri sciureus, Felis catus, Sus, Canis familiaris, Cavia rodentia and Oryctalagis cuniculus during exogenous glucose deprivation. 2. These differences were not attributable to differences in endogenous glycogen stores, and appear instead to emanate from comparative species differences in lenticular enzyme activities.


Microhabitat use in a mediterranean riverine fish assemblage : Fishes of the upper Matarraña.
We examined microhabitat use in Barbus graellsii, Barbus haasi, Chondrostoma toxostoma, Rutilus arcasii, and Salmo gairdneri over a 19 month period in the upper Rio Matarraña, Spain. B. graellsii and Ch. toxostoma exhibited non-random microhabitat use during all seasons and preferentially occupied deep microhabitats with heterogeneous substrates. During the majority of seasons in which they were present, B. haasi and R. arcasii occurred in microhabitats similar to those occupied by B. graellsii and Ch. toxostoma. S. gairdneri was over-represented in high velocity microhabitats with erosional substrates. We did not observe any evidence of interspecific interference competition or avoidance. Substrate composition did not appear to affect microhabitat use outside of its covariation with depth and velocity. Seaonal variation in microhabitat use by B. graellsii, B. haasi and Ch. toxostoma was strongly correlated with seasonal changes in microhabitat availability. S. gairdneri, however, occurred closer to the substrate when average velocities were high. Larger B. graellsii and B. haasi sometimes occupied deeper, higher velocity microhabitats than did smaller specimens. Larger B. graellsii also occasionally occurred farther from shelter than did smaller specimens; the reverse was true for B. haasi. Larger Ch. toxostoma sometimes were found farther from both the substrate and shelter than smaller individuals, whereas smaller specimens occasionally inhabited deeper areas with more depositional substrates than did larger Ch. toxostoma. During Late Summer 1985, smaller Ch. toxostoma also occupied microhabitats with higher velocities than did larger specimens. A comparison of microhabitat use for two species present in both upper and lower portions of the Matarraña indicated that most differences in microhabitat use could be attributed to inter-site differences in microhabitat availability. The data suggest, hovever, that both species shifted to more protected microhabitats in the higher velocity site. Assemblage members generally occupied statistically distinguishable microhabitats and could be classified as: 1) high-velocity upper water column (S. gairdneri), 2) low velocity lower water column (B. graellsii, Ch. toxostoma and R. arcasii), and 3) shelter-oriented benthic (B. haasi). The introduction of S. gairdneri during Winter 1984 did not produce microhabitat shifts in any of the native species. Whether or not the native species affected microhabitat use in S. gairdneri is unknown. Interspecific competition for space, however, did not appear to strongly influence microhabitat use among the native species.


Melittin-stimulated arachidonic acid metabolism by cultured malignant human epidermal keratinocytes.
Upon melittin stimulation, cultured SCC-13 keratinocytes release prostaglandins E2, F2 alpha, 6-keto-F1 alpha, thromboxane B2, leukotriene B4, and 6-sulfido-peptide-containing leukotrienes (SRS) into serum free medium. Release of prostaglandins E2, F2 alpha, and SRS, normalized to cell protein, is 3- to 10-fold higher from rapidly growing than confluent cultures. Cells growing with hydrocortisone in the medium produce approximately twice the level of the cyclooxygenase-mediated metabolites PGE2 and PGF2 alpha as those without hydrocortisone, but similar levels of the lipoxygenase-mediated metabolite SRS. The results demonstrate the potential utility of squamous carcinoma lines for investigating biochemical pathways of arachidonic acid metabolism in keratinocytes.


Gestational change of K+ channel opener effect is correlated with the expression of uterine KATP channel subunits.
We analyzed the gestational changes of pharmacological activity and molecular levels of KATP channels in rat myometrium. Using rat myometrium, the effects of K+ channel openers (KCOs) were examined in an isometric tension study of oxytocin-induced contraction. We also examined the effects of KCOs on the intracellular Ca2+ levels of cultured myometrial cells. The expression of myometrial KATP channels was assessed by RT-PCR and Northern blot analysis. The effect of KCOs were altered during pregnancy, with a significant increase of their potency at day 18 of pregnancy followed by a decline towards the non-pregnant level at the day of delivery. KCOs suppressed the Ca2+ influx across the cell membrane. The mRNAs encoding each component of myometrial KATP channels, Kir6.1 and SUR2B, exhibited gestational stage-dependent alterations similar to those of the effects of KCOs. These findings suggest that KCOs inhibit uterine myometrial contraction more effectively during pregnancy than in the non-pregnant state due to gestation-enhanced expression of KATP channels, implying that KCOs might be useful for preventing premature delivery.


Therapeutic drug monitoring of once daily tobramycin in cystic fibrosis--caution with trough concentrations.
: Once daily intravenous aminoglycoside dosing (ODD) is widely used to treat acute Pseudomonas aeruginosa exacerbations in patients with cystic fibrosis. Controversy exists as to what is the most appropriate method of therapeutic drug monitoring (TDM) of such therapy with recommendations including trough plasma concentrations of <1 mg/L or <2 mg/L, area under curve (AUC) and various nomograms. This study aimed to compare the exposures to ODD of tobramycin in adults and children with cystic fibrosis using the AUC and trough TDM approaches. : Using a mono-exponential software program to calculate AUC from 2 plasma concentrations, AUCs were determined in 22 adults with pre-dose tobramycin concentrations <1 mg/L. The exposure of 5 children with reduced tobramycin clearances was simulated at the usual recommended dose of 10 mg/kg/daily but retaining a trough <1 mg/L. : A tobramycin dose of 10 mg/kg of tobramycin in these patients with normal serum creatinine and a trough concentration <1 mg/L resulted in exposures in excess of those associated with conventional 8-hourly dosing. : The TDM approach of a trough <1 mg/L, as used with conventional 8-hourly tobramycin dosing, is not relevant to ODD.


Deubiquitylase PSMD14 inhibits autophagy to promote ovarian cancer progression via stabilization of LRPPRC.
Autophagy is a key cellular process, which exists in many tumors and plays dual roles in tumor promotion and suppression. However, the role and mechanism of aberrant autophagy in ovarian cancer remains unclear. Ubiquitin-proteasome pathway is the most important pathway for specific protein degradation. Deubiquitinases (DUBs) have crucial roles in all the stages of tumorigenesis and progression. Herein, we explore the DUBs which contribute to aberrant autophagy in ovarian cancer. TCGA data analysis shows that the autophagy level is suppressed, and the selective autophagy receptor SQSTM1/p62 is abnormally high expressed in ovarian cancer. We screen and identify that the deubiquitinase PSMD14 negatively regulates autophagy level. Functional studies show that increased PSMD14 expression remarkably enhances ovarian cancer cells malignancy, whereas knockdown of PSMD14 has the opposite effect. Furthermore, in vivo assays show that knockdown of PSMD14 inhibits the growth, lung and abdominal metastasis of ovarian cancer. Mechanistically, PSMD14 directly interacts with LRPPRC and inhibits its ubiquitination, thereby inhibiting autophagy through LRPPRC/Beclin1-Bcl-2/SQSTM1 signaling pathway. Next, we demonstrate that PSMD14 is upregulated in ovarian cancer and high expression of PSMD14 positively correlates with LRPPRC. Taken together, we clarify the role of autophagy in regulating the ovarian cancer phenotype and provide insights into regulatory mechanism of autophagy in ovarian cancer.


Factors associated with mental health of internal migrants (Kayayei) in Agbogbloshie-Ghana.
The United Nations (UN) Sustainable Development Goal (SDG) Eight (8) advocates for decent work and improved economic outcomes for all. However, internal migrant workers in Ghana, especially female head porters, commonly known as "Kayayei", work in exploitative and hazardous conditions exposing them to physical and mental health risks. Yet, mental health among this vulnerable group of migrants has not been given the needed attention it deserves in the country. We, therefore, examined the factors associated with mental health challenges among internal migrants (Kayayei) in Ghana. A cross-sectional study among a systematic random sample of 352 Kayayei was conducted in Agbogbloshie-Accra, Ghana. An interviewer-administered questionnaire was used to collect data on the factors impacting the mental health of Kayayei. The study used binary logistic regression in predicting factors impacting mental health distress at a 0.05 level of significance and 95% confidence interval. The prevalence of depression, anxiety, and stress were, 305 (86.6%), 332 (94.4), and 149 (42.4), respectively, with 147(41.1%) of respondents having all three mental health issues. The difficult nature of work significantly predicted depression, anxiety, and stress. Respondents who perceived their work as very difficult were 4.3 times, (aOR = 4.36, 95% CI = 2.17, 8.76, p = < 0.001), 3.66 times (aOR = 3.66, 95% CI = 1.37, 9.76, p = 0.009), and 1.73 times (aOR, = 1.73, 95% CI = 1.04, 2.85, p = < 0.009) more likely to be depressed, anxious, and stressed respectfully as compared to those who rate their work as just difficult. The majority of the Kayayei suffered from mental health distress (depression, anxiety, and Stress) due to their work circumstances. This study suggests that the Ghana Labour Commission must extend the Labour Act 2003(Act 651) to cover the informal sector and create awareness among the Kayayei community to know their rights and report any abuse to law enforcement agencies. It is also suggested that the government, NGOs, and other benevolent organisations train the Kayayei to attain alternative and sustained livelihoods that will not negatively impact their mental health as has been found in the current study. Finally, the government should fully implement the 2012 Mental Health Act to increase awareness and access to quality mental health care.


Clonal hematopoiesis, multi-omics and coronary artery disease.
Studies of the genetic architecture of cardiovascular disease once focused on heritable germline factors. Newer work has shed light on the role of somatic mutations in blood cells. These mechanistic and multi-omics studies, along with phenotypic analyses, offer the prospect of new precision cardiovascular medicine paradigms.


Influence of cationic lipid concentration on properties of lipid-polymer hybrid nanospheres for gene delivery.
Nanoparticles have been widely used for nonviral gene delivery. Recently, cationic hybrid nanoparticles consisting of two different materials were suggested as a promising delivery vehicle. In this study, nanospheres with a poly(D,L-lactic-co-glycolic acid) (PLGA) core and cationic lipid shell were prepared, and the effect of cationic lipid concentrations on the properties of lipid polymer hybrid nanocarriers investigated. Lipid-polymer hybrid nanospheres (LPHNSs) were fabricated by the emulsion-solvent evaporation method using different concentrations of cationic lipids and characterized for size, surface charge, stability, plasmid DNA-binding capacity, cytotoxicity, and transfection efficiency. All LPHNSs had narrow size distribution with positive surface charges (ζ-potential 52-60 mV), and showed excellent plasmid DNA-binding capacity. In vitro cytotoxicity measurements with HEK293T, HeLa, HaCaT, and HepG2 cells also showed that LPHNSs exhibited less cytotoxicity than conventional transfection agents, such as Lipofectamine and polyethyleneimine-PLGA. As cationic lipid concentrations increased, the particle size of LPHNSs decreased while their ζ-potential increased. In addition, the in vitro transfection efficiency of LPHNSs increased as lipid concentration increased.


Differential ear growth of two maize varieties to shading in the field environment: Effects on whole plant carbon allocation and sugar starvation response.
The interception of irradiation by smog pollution and cloud cover associated with extreme rainfall events has become an increasingly important limiting factor in crop production in China. Little is known about the adaptation of carbon (C) allocation to periodic low irradiance in field conditions. The trehalose signaling pathway plays a critical role in adapting C allocation to the environment in crops but its importance in adaptation to low light in field conditions is not known. To determine the effects of low irradiance on C economy and maize yield, two commonly grown hybrids (LY-16 and ZD-958) were subject to three levels of shading (15 %, 50 %, and 97 %) for one week from V13 stage in two successive seasons. Shading led to yield loss mainly due to decreased kernel number, which was greater in LY-16 than ZD-958. Effects of shading on leaf area and photosynthesis were similar in both varieties. Starch levels in leaves were maintained, whereas total soluble carbohydrates were reduced up to fivefold by shading in both varieties. Shading increased the proportion of photoassimilate retained in leaves relative to reproductive organs. Carbohydrates in ears and stem were decreased by shading similarly in both varieties. Amongst the parameters measured, the main difference between LY-16 and ZD-958 associated with yield penalty was the expression of class II trehalose phosphate synthase (TPS) and trehalose-6-phosphate phosphatase (TPP) genes which were increased due to shading in leaves and ears, particularly in ears of LY-16. It is concluded that altered C fixation and allocation by low irradiance limited ear growth at pre-anthesis. Activation of TPSII and TPP genes indicates that the trehalose pathway likely plays a role in ear development under low light and could be a target for yield improvement under such conditions as with other stresses.


Relaxing effects of adenosine in coronary artery in calcium-free medium.
Adenosine relaxes the coronary arteries of various species through A2 receptors. The mechanism(s) by which adenosine causes relaxation of the coronary smooth muscle through changes in intracellular Ca levels is not understood. Therefore, the aim of this study was to evaluate the vasodilatory action of adenosine in normal and in Ca-free medium and the effect of adenosine on 45Ca efflux in Ca-free medium. Prostaglandin F2 alpha (10(-5) M) was used to induce tone in bovine coronary artery rings both in the presence and absence of Ca. Adenosine, 5'-N-ethyl-carboxamide adenosine (NECA) and N6-L-phenyl-isopropyl adenosine (L-PIA) produced concentration-dependent relaxation of the coronary artery rings when precontracted with prostaglandin F2 alpha. Both in normal and Ca-free medium, the order of potency for adenosine analogs (NECA greater than L-PIA greater than adenosine) was similar and 8-phenyltheophylline antagonized the relaxation response to adenosine and its analogs. In Ca-free medium, the concentration-response curves for adenosine and its analogs were shifted to the right, in a parallel fashion, from the curves obtained in Ca-containing solution. Removal of extracellular Ca reduced the maximum responses and slowed the rate of relaxation of adenosine and its analogs and the KB values for 8-phenyltheophylline were significantly increased. In Ca-free medium, adenosine was without an effect on 45Ca efflux in the presence of prostaglandin F2 alpha. The data suggest that the coronary vasodilatory action of adenosine has both extracellular Ca-dependent and -independent components.


Self-efficacy and self-motivation as predictors of weight loss.
The present study was attempted to determine whether self-efficacy and self-motivation would predict outcome in an intensive weight loss program. The subjects included 52 males and 95 females who were at least fifty pounds overweight (mean age = 43 years). The data were analyzed through multiple regression on three separate dependent variables: actual weight loss, adjusted weight loss and percentage of sessions attended. Outcome was predicted based on the following variables: self-efficacy (as measured by confidence estimates and outcome expectancies) and self-motivation (as measured by the Self-Motivation Inventory). The predictors accounted for 32.2% (p less than .01) of the variance in actual weight loss, 8.5% (p less than .01) of the variance in adjusted weight loss and none of the variance in percentage of sessions attended. Self-motivation did not correlate significantly with either actual or adjusted weight loss, while self-efficacy measures did. However, the correlation of the two self-efficacy measures (r = -.07, p greater than .05) suggests that these variables do not constitute a unitary construct and should be conceptualized as independent predictors. These findings suggest that confidence estimates and outcome expectancies are useful predictors of weight loss.


Chest Pain and ST-Segment Elevation in an 18-Year-Old Man.
An 18-year-old man came to the hospital because of 1 day of chest pain typical of pericarditis. He had had an upper respiratory infection 10 days earlier. His electrocardiograms indicated evolving pericarditis. His echocardiogram showed mild, diffuse left ventricular hypokinesia, and his troponin I level peaked at 47.5 ng/ml. Thus, he had myopericarditis.


Human papillomavirus and human telomerase RNA component gene in cervical cancer progression.
This study aimed to examine hTERC gene in different grades of cervical intraepithelial neoplasia (CIN) and cervical cancer, and the association between hTERC and high risk-human papillomavirus (HR-HPV) infection. Patients who underwent cervical cancer screening at the Second Affiliated Hospital of Kunming Medical University between October 2010 and December 2011 were enrolled. All patients underwent liquid-based cytology test and hybrid capture 2 (HC2) for HPV detection. hTERC was examined using fluorescence in situ hybridization (FISH). Cervical colposcopy biopsy was performed if any of the three results was positive. HC2, FISH, and pathology were compared. A total of 1200 women underwent screening, 150 patients underwent cervical biopsy: 32 in the normal group, 38 in the CIN1 group, 66 in the CIN2/3 group, and 14 in the invasive cervical cancer group. More patients had HR-HPV infection in the CIN2/3 group and ICC group compared with the CIN1 group. hTERC increased with increasing histological dysplasia. There was significant difference in hTERC positive rate between each of the three groups. More patients with hTERC gene amplification were observed in the positive HR-HPV group than in the HR-HPV negative group. In conclusion, hTERC is a potential marker for precancerous cervical cancer lesions. hTERC might be correlated with HR-HPV infection in cervical diseases.


Modulation of MUC1 and blood group antigen expression in gastric adenocarcinoma cells by cytokines.
Immunohistological studies demonstrated that MUC1 expression in gastric cancer is associated with a poor prognosis. As a mediator of cell-cell interactions, MUC1 may also be involved in metastasis. However, these aspects are of relevance since cytokine levels are locally increased as a consequence of peritumorous inflammatory response and coexisting chronic gastritis. Therefore we analyzed the potential influence of several cytokines on the expression of tumor-associated MUC1 and Lewis blood group antigens in gastric carcinoma cells. Gastric cancer cell lines AGS and KATOIII were incubated with the cytokines interleukin-1beta, interferon-gamma, tumor necrosis factor-alpha (TNF-alpha), and hepatocyte growth factor over a period of 72 h. Expressions of mucin antigens and cytokine secretion were measured by immunocytochemistry and/or enzyme-linked immunosorbent assay (ELISA). Analysis by fluorescence-activated cell sorter (FACS) demonstrated that MUC1 and sialyl Lewis A reactivities of AGS cells were increased significantly following TNF-alpha stimulation but not by other cytokines. Expression of mucin-associated antigens by cell line KATOIII was not affected by any of the employed cytokines. These data provide evidence that TNF-alpha can raise the expression of important mucin peptide as well as mucin-associated carbohydrate antigens and thereby potentially influence the progression of gastric carcinomas.


Iron transfer from ferritin to transferrin. Effect of serum factors.
The transfer of iron from 59Fe-labelled human spleen ferritin to human apotransferrin occurs in the absence of either reducing or chelating agents. The reaction is first order with respect to ferritin and zero order to apotransferrin. The transfer is enhanced by low-Mr substances from human serum such as ascorbate, citrate, bicarbonate and lactate. A mixture of the four molecules at their normal physiological concentrations can increase the iron exchange to the same extent as that observed with an ultrafiltrate of serum. A pathway of intracellular iron mobilization is considered.


[Correlations between nephrotomography and arteriography in the diagnosis of renal mass lesions (author's transl)].
A series of 325 patients with renal mass lesions were examined by means nephrotomography during the years 1973-76; 85 of them (26%) underwent angiographic investigations. The basic findings observed with nephrotomography are described followed by the criteria which have suggested the necessity of the arteriographic examination. The analysis of the correlations between the two methods, shows the criteria which may limit the use of renal arteriography.


Modulation of T-cell-mediated regulation of antibody production by interaction with specific immune complexes.
The importance of the phlogogenic effects of immune complexes in disease pathogenesis has been emphasized, but they also have a role in immunoregulation. We examined the effects of DNA: anti-DNA immune complexes, formed at different antigen:antibody ratios, on the ability of T cells to modulate DNA antibody production in vitro. We found that antigen-excess complexes promote IgM anti-DNA synthesis, whereas antibody-excess complexes favor a switch to IgG anti-DNA production. We suggest that interaction of T cells with immune complexes is an important feedback mechanism in control of the immune response.


Electroencephalogram (EEG) dataset with porn addiction and healthy teenagers under rest and executive function task.
The electroencephalogram (EEG) signal data were obtained from Yayasan Kita dan Buah Hati (YKBH), Jakarta, Indonesia and collected using a Brain Maker EEG machine with 19 channels. The sampling rate of the machine was 250 Hz. Fourteen participants (five females and nine males) participated in the data collection. A psychologist verified that seven of them were addicted to porn, and seven were healthy teenagers. The EEG data were recorded using one protocol with nine tasks for 10 min. The three stages were the baseline (tasks with eyes closed and open), emotional state (happy, calm, sad and fearful tasks) and main (15-words memorisation task, executive task and 15-words recall task) stages. The data obtained was used to analyse the signal pattern of pornography addiction amongst teenagers, as well as the emotional signal pattern and working memory capacity.


Promoting substance use education among generalist physicians: an evaluation of the Chief Resident Immersion Training (CRIT) program.
Education about substance use (SU) disorders remains inadequate in medical training. To describe the Chief Resident Immersion Training (CRIT) program in addiction medicine and to evaluate its impact on chief resident (CR) physicians' substance use knowledge, skills, clinical practice, and teaching. A controlled educational study of CRIT programs (2003, 2004, and 2005) for incoming CRs in generalist disciplines. Intervention CRs were trained to diagnose, manage, and teach about SU. The control CRs sought but did not receive the intervention. Eighty-six CR applicants to the CRIT program. Baseline and 6-month questionnaires assessing substance use knowledge, skills, clinical practice, and teaching. Outcomes were compared within groups from baseline to follow-up and between groups at follow-up. The intervention (n = 64) and control (n = 22) CRs were similar demographically. At 6-month follow-up, the intervention CRs reported a significant increase in SU knowledge, confidence, and preparedness to diagnose, manage, and teach and an increase in SU clinical and teaching practices compared to their baseline and control CRs. This intensive training for chief residents (CRs) improved knowledge, confidence, and preparedness to diagnose, manage, and teach about substance use (SU), affecting both the CRs' SU clinical and teaching practices. The CRIT program was an effective model for dissemination of SU knowledge and skills to educators in a key position to share this training with a broader audience of medical trainees. This model holds potential to address other high priority medical, yet under-addressed, content areas as well.


Acute Toxicity of a Novel anti-fouling Material Additive DCOIT to Marine Chlorella sp.
DCOIT (4,5-dichloro-2-n-octyl-4-isothiazolin-3-one) is the main ingredient in SeaNine-211, a new antifouling agent that replaces organotin compounds to prevent the growth of fouling organisms on board. Biocides from antifoulants can cause problems for marine ecosystems by destroying non-target algal species. This study evaluated the potential adverse effects DCOIT using the Marine Chlorella sp. The concentration of DCOIT were set according to the semi-inhibitory concentrations for acute exposure experiments, and relevant oxidative stress indicators were measured to assess the acute toxic effects. The results showed that the inhibition concentrations (IC50) of DCOIT against Marine Chlorella sp was 2.522 mg/L. The genes related to photosynthesis and antioxidant capacity showed the effect of promoting low concentration and inhibiting high concentration. In addition, based on the ultrastructural observation and the expression analysis of photosynthesis related genes, it was found that DCOIT had a significant effect on plant photosynthesis.


The orientation of iron-sulfur clusters and a spin-coupled ubiquinone pair in the mitochondrial membrane.
Oriented multilayers made from beef heart and yeast mitochondria and submitochondrial particles were studied using electron paramagnetic resonance. EPR signals from membrane-bound iron-sulfur clusters and from a spin-coupled ubiquinone pair are highly orientation dependent, implying that these redox centers are fixed in the membrane at definite angles relative to the membrane plane. Typically the iron-iron axis (gz) of the binuclear iron-sulfur clusters is in the membrane plane. This finding is discussed in terms of the protein structure. The tetranuclear iron-sulfur clusters can have their gz axis either perpendicular or parallel to the membrane plane, but intermediate orientation was not observed.


[Neurofibromatosis].
Neurofibromatoses regroup at least two different autosomal dominant disorders, neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). NF1 gene and NF2 genes have been respectively localized on chromosomes 17 and 22. NF1 represents 95% of neurofibromatoses cases. Its incidence is 1 for 3,500 newborns, its prevalence 1 for 4,500. NF1 is characterized by its cutaneous manifestations, café au lait spots, lentigines and neurofibromas. NF2 incidence is 1 for 33,000-40,000 newborns. NF2 is characterized by bilateral vestibular schwannomas (former acoustic neurinomas) and other tumors of the central nervous system. The hallmark of schwannomatosis (neurilemmomatosis) is multiple cutaneous or subcutaneous schwannomas without vestibular schwannomas. Different neurofibromatoses are characterized by different prognosis, complications, and genetic counseling. Multidisciplinary centers with trained physicians are ideal structures for management of neurofibromatoses patients.


Left ventricular ejection fraction determined with the simulation of a very low-dose CZT-SPECT protocol and an additional count-calibration on planar radionuclide angiographic data.
To determine whether the left ventricular ejection fractions (EFs), measured on a high-sensitivity CZT single photon emission computed tomography (SPECT)-camera with a 70% reduction in recording times and a prevention of EF overestimation through an additional count-calibration, are concordant with reference EF from planar radionuclide angiography (2D-RNA). An additional 10-minute CZT-SPECT recording was performed in patients referred to 2D-RNA for cardiomyopathy (n = 23) or chemotherapy monitoring (n = 50) with an in vivo red blood cell labeling with 850 MBq [Formula: see text]. The EF, obtained from CZT-SPECT with 100% (SPECT100) or 30% (SPECT30) projection times and with a SPECT-count calibration on the 2D-RNA counts of corresponding cavity volumes, were compared to EF from 2D-RNA. Strong and equivalent relationships were documented between the EF from 2D-RNA and the calibrated EF from SPECT100 (y = 0.89x + 6.62; R2 = 0.87) and SPECT30 (y = 0.87x + 8.40; R2 = 0.85), and the mean EF from SPECT100 (54% ± 15%) and SPECT30 (53% ± 16%) were close to that from 2D-RNA (55% ± 15%). However, upward shifts in these mean values were documented in the absence of count calibration for both SPECT100 (60% ± 18%) and SPECT30 (60% ± 18%). Left ventricular EF may be determined on a high-sensitivity CZT-camera, a 70% reduction in injected activities, and an additional count-calibration for further enhancing the concordance with 2D-RNA values.


Two types of GABA-containing axon terminals in cerebellar glomeruli of cat: an immunogold-EM study.
Immunogold demonstration of GABA was used in ultrathin sections of cerebellar cortex of cat to identify GABA(+) profiles in cerebellar glomeruli. In addition to small, GABA-containing axonal varicosities found at the periphery of all glomeruli, a few complex glomeruli were found to contain a second type of GABA(+) terminal, with a mossy ending appearance. GABA(+) type "I" axon terminals, which were identified as the axonal arborization of local Golgi cells, contained ovoid, small synaptic vesicles. GABA(+) type "II" terminals, however, exhibited large, spheroid synaptic vesicles. Experimental evidence is provided that type "II" GABA(+) mossy like terminals are the endings of nucleocortical fibers.


Stochastic switching to competence.
Distinct modes of gene expression enable isogenic populations of bacteria to maintain a diversity of phenotypes and to rapidly adapt to environmental changes. Competence development for DNA transformation in Bacillus subtilis has become a paradigm for a multimodal system which implements a genetic switch through a nonlinear positive feedback of a transcriptional master regulator. Recent advances in quantitative analysis at the single cell level in conjunction with mathematical modeling allowed a molecular level understanding of the switching probability between the noncompetent state and the competent state. It has been discovered that the genetic switching probability may be tuned by controlling noise in the transcription of the master regulator of competence, by timing of its expression, and by rewiring of the control circuit.


Efficient complexation of N-acetyl amino acid carboxylates in water by an artificial receptor: unexpected cooperativity in the binding of glutamate but not aspartate.
A new tris-cation 1 binds N-acetyl amino acid carboxylates in water even at millimolar salt concentrations with Kass approximately 103 M-1 due to a clustering of electrostatic interactions. Binding is efficient enough to allow a naked-eyed detection using an indicator displacement assay. Furthermore, receptor 1 shows an unexpected 2:1 complex formation with strong positive cooperativity with glutamate but not aspartate.


Incidence and Predictors of Structural Valve Deterioration after Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis.
Transcatheter aortic valve replacement (TAVR), widely used as an alternative therapy in patients with severe aortic stenosis, is expected to be offered to low-risk patents with a longer life expectancy. The durability of transcatheter aortic valve is becoming of increasing importance. PubMed, Embase, and Cochrane CENTRAL from the inception to March 2020 were systematically screened for studies reporting on structural valve deterioration (SVD) in TAVR patients. Incidence of SVD was diagnosed according to the latest European consensus as the primary end point. Predictors of SVD evaluated at multivariable analysis and cumulative incidence function (CIF) of SVD were the secondary end point. Twelve studies encompassing 10031 patients evaluating the incidence of SVD were included, with a follow-up between 1 and 8 years. The pooled incidence of SVD was 4.93% (95% CI, 2.75%-7.70%, I 2 = 96%) at 1 year and 8.97% (95% CI, 6.89%-11.29%, I 2 = 86%) in the long term (≥5 years). Subgroup analysis was performed to identify the valve type that may result in partial heterogeneity. SVD was more frequent in patents with a valve diameter of <26 mm (HR: 3.57, 1.47-8.69), oral anticoagulants (OAC), exposure at discharge (OR: 0.48, 0.38-0.61), or by a disease of renal dysfunction (OR 1.42, 1.03-1.96). SVD represents infrequent events after TAVR in the long term (>5 years), occurring more commonly in renal dysfunction patients, with small valve diameter and without OAC exposure. There may be an underestimation of the incidence if we assume death as a competing risk.


Presentation and Clinical Outcomes of Choledochal Cysts in Children and Adults: A Multi-institutional Analysis.
Choledochal cysts (CCs) are rare, with risk of infection and cancer. To characterize the natural history, management, and long-term implications of CC disease. A total of 394 patients who underwent resection of a CC between January 1, 1972, and April 11, 2014, were identified from an international multi-institutional database. Patients were followed up through September 27, 2014. Clinicopathologic characteristics, operative details, and outcome data were analyzed from May 1, 2014, to October 14, 2014. Resection of CC. Management, morbidity, and overall survival. Among 394 patients, there were 135 children (34.3%) and 318 women (80.7%). Adults were more likely to present with abdominal pain (71.8% vs 40.7%; P < .001) and children were more likely to have jaundice (31.9% vs 11.6%; P < .001). Preoperative interventions were more commonly performed in adults (64.5% vs 31.1%; P < .001), including endoscopic retrograde pancreatography (55.6% vs 27.4%; P < .001), percutaneous transhepatic cholangiography (17.4% vs 5.9%; P < .001), and endobiliary stenting (18.1% vs 4.4%; P < .001)). Type I CCs were more often seen in children vs adults (79.7% vs 64.9%; P = .003); type IV CCs predominated in the adult population (23.9% vs 12.0%; P = .006). Extrahepatic bile duct resection with hepaticoenterostomy was the most frequently performed procedure in both age groups (80.3%). Perioperative morbidity was higher in adults (35.1% vs 16.3%; P < .001). On pathologic examination, 10 patients (2.5%) had cholangiocarcinoma. After a median follow-up of 28 months, 5-year overall survival was 95.5%. On follow-up, 13 patients (3.3%), presented with biliary cancer. Presentation of CC varied between children and adults, and resection was associated with a degree of morbidity. Although concomitant cancer was uncommon, it occurred in 3.0% of the patients. Long-term surveillance is indicated given the possibility of future development of biliary cancer after CC resection.


Hepatic sinusoids in liver injury, inflammation, and fibrosis: new pathophysiological insights.
Changes of hepatic sinusoids are crucial in the pathogenesis of liver cirrhosis and portal hypertension. Liver injury leads to distinct morphological abnormalities such as loss of sinusoidal fenestration, vasoconstriction, and angiogenesis as well as molecular changes. Communication between the two key cells in this hepatic microenvironment-hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC)-has been studied for many years and several canonical pathways have been elucidated, such as decreased eNOS activity or increased PDGF and TGF-β production leading to activation and migration of HSC. In recent studies, alternative pathways of intercellular communication in liver diseases have been described such as cell-derived extracellular vesicles called exosomes, which deliver cell compounds to their target cells. Moreover, such extracellular vesicles may link injury to inflammation in alcoholic hepatitis. While inflammation leading to liver fibrosis has been studied in detail, in some circumstances pathways other than the known canonical inflammatory pathways may contribute to hepatic fibrogenesis. For example, in congestive hepatopathy, sinusoidal dilatation and fibrosis have been shown to be mediated by non-inflammatory mechanisms and associated with sinusoidal thrombi. A recently developed murine model further enables experimental studies of this disease entity. Increasing knowledge about these alternative disease pathways in liver injury, inflammation, and fibrosis may reveal possible target molecules for future therapies. This article builds upon a seminar given at the recent 3rd JSGE International Topic Conference in Sendai, Japan, and reviews the areas outlined above.


Retinoid stability and degradation kinetics in commercial cosmetic products.
Retinoids as dermatological agents are effective against acne, psoriasis, skin aging, and other skin conditions. However, their susceptibility to degradation is a limiting factor for their widespread use. Within this study, we aimed to provide comprehensive and evidence-based information on retinoid stability and degradation kinetics in commercial cosmetics, focusing on different factors affecting their stability. A validated HPLC-UV methodology was utilized for determination of the most common retinoids in cosmetics (retinol, retinyl palmitate, β-carotene) and a newer promising retinoid (hydroxypinacolone retinoate). The stability of 16 retinoid derivatives in 12 commercial cosmetics was evaluated within 6 months of long-term and accelerated stability testing in addition to a one-week photostability study. Retinoid degradation in the tested formulations followed first-order kinetics, which was further applied to shelf-life prediction. Long-term and accelerated stability testing revealed retinoid instabilities in almost all products, resulting in a 0%-80% decline after 6 months at 25°C and a 40%-100% decline at 40°C, which were kinetically evaluated. Light degradation was more pronounced than temperature-induced degradation. Among the studied retinoids, the stability of the newer hydroxypinacolone retinoate was the most prominent. This study also identifies correlations between retinoid concentrations, price, formulation, and their stability in cosmetics. Retinoid instabilities were formulation-dependent and associated with lower contents than declared in some cosmetics. Retinoid chemical stability and physical stability in topical formulations need to be evaluated by real-time stability studies, instead of the more frequently used accelerated stability studies.


Conformational and NMR study of some furan derivatives by DFT methods.
4'-substituted neutral/protonated furfurylidenanilines and trans-styrylfurans are able to exist in two different conformations related to the rotation around the furan ring-bridge double bond. In this work, the equilibrium geometry and the corresponding rotational barrier of the benzene ring for each furan derivative conformation were calculated by DFT methods. The trend and shape of the rotational barrier are rationalized within natural bond orbitals as well as atoms-in-molecules approach. For the corresponding equilibrium geometries, (1)H and (13)C substituent induced shifts (SIS) were calculated and compared with experimental values. Calculated shielding constants are shown to be sensitive to the substituent effect through a linear fit with substituent's Hammett constants. An alternative approach was followed for assessing the effect of substituents over SIS through comparing the differences in isotropic shielding constants with NBO charges as well as with (1)H and (13)C experimental chemical shifts.


Training and standardization of simulated patients for multicentre studies in clinical pharmacy education.
To evaluate the training and standardization methods of multiple simulated patients (SPs) performing a single scenario in a multicenter study. A prospective quasi-experimental study, using a multicenter approach, evaluated the performance of five different individuals with the same biotype during a simulation session in a high-fidelity environment. The SPs training and standardization process consisted of four steps and six web or face-to-face mediated: Step 1: simulation scenario design and pilot test. Step 2: SPs selection, recruitment and beginning training (Session 1: performance instructions and memorization request.) Session 2: check the SPs' performances and adjustments). Step 3 and session 3: training role-play and performance's evaluation. Step 4: SPs' standardization and performances' evaluation (Sessions 4 and 5: first and second rounds of SPs' standardization assessment. Session 6: Global training and standardization evaluation. SPs performance consistency was estimated using Cronbach's alpha and ICC. In the evaluation of training results, the Maastricht Simulated Patient Assessment dimensions of SPs performances "It seems authentic", "Can be a real patient" and "Answered questions naturally", presented "moderate or complete agreement" of all evaluators. The dimensions "Seems to retain information unnecessarily", "Remains in his/her role all the time", "Challenges/tests the student", and "Simulates physical complaints in an unrealistic way" presented "moderate or complete disagreement" in all evaluations. The SPs "Appearance fits the role" showed "moderate or complete agreement" in most evaluations. In the second round of evaluations, the SPs had better performance than the first ones. This could indicate the training process's had good influence on SPs performances. The Cronbach's alpha in the second assessment was better than the first (varied from 0.699 to 0.978). The same improvement occurred in the second round of intraclass correlation coefficient that was between 0.424 and 0.978. The SPs were satisfied with the training method and standardization process. They could perceive improvement on their role-play authenticity. The SPs training and standardization process revealed good SPs reliability and simulation reproducibility, demonstrating to be a feasible method for SPs standardization in multicenter studies. The Maastricht Simulated Patient Assessment was regarded as missing the assessment of the information consistency between the simulation script and the SPs provision.


Deazaflavin reductive photocatalysis involves excited semiquinone radicals.
Flavin-mediated photocatalytic oxidations are established in synthetic chemistry. In contrast, their use in reductive chemistry is rare. Deazaflavins with a much lower reduction potential are even better suited for reductive chemistry rendering also deazaflavin semiquinones as strong reductants. However, no direct evidence exists for the involvement of these radical species in reductive processes. Here, we synthesise deazaflavins with different substituents at C5 and demonstrate their photocatalytic activity in the dehalogenation of p-halogenanisoles with best performance under basic conditions. Mechanistic investigations reveal a consecutive photo-induced electron transfer via the semiquinone form of the deazaflavin as part of a triplet-correlated radical pair after electron transfer from a sacrificial electron donor to the triplet state. A second electron transfer from the excited semiquinone to p-halogenanisoles triggers the final product formation. This study provides first evidence that the reductive power of excited deazaflavin semiquinones can be used in photocatalytic reductive chemistry.


High Perirenal Fat Volume Affect Negatively Renal Function in Living Renal Transplantation.
We aimed to investigate the effect of perirenal fat volume (PFV) on graft functions by calculating the PFV of donor kidney with routine computed tomography before renal transplantation. From May 2019 to December 2020, a total of 54 living donors and recipients who met the criteria for kidney donor were included in the study. Left donor nephrectomy was performed to all donors. Data of age, sex, body mass index (BMI), PFV of the donors, estimated glomerular filtration rate (eGFR), and serum creatinine measurement data of the recipients were recorded. Serum creatinine and eGFR of the recipients were recorded at the 12th month controls. The patients were sorted into 2 groups (G) according to their GFR values. G1, GFR <60 mL/min/1.73 m2; G2, GFR ≥ 60 mL/min/1.73 m2. There was no difference in terms of recipient sex, recipient age, donor sex, recipient BMI, and donor BMI between the 2 groups. The mean of PFV was higher in G1 and was statistically significant (P= 0.01). The ability of the donor BMI and PFV to predict G2 was evaluated by receiver operating characteristic curve analysis. It was determined that PFV predicted G2 to be statistically significant. In the multivariate logistic regression analysis, PFV (odds ratio = 0.988, 95% GA = 0.977-0.999, P = 0.03) was found as an independent predictor of G2. In conclusion, our study showed PFV as an independent risk factor for low eGFR, revealing that the previously documented relevance of increased BMI with a low eGFR can be partially explained by PFV.


Therapeutic targeting of PRAME with mTCRCAR T cells in acute myeloid leukemia.
Preferentially Expressed Antigen in Melanoma (PRAME), a cancer-testis antigen, provides an ideal target for immunotherapy in acute myeloid leukemia (AML). We have shown expression of PRAME in a significant subset of childhood and adult AML and lack of expression in normal hematopoiesis. Although an intracellular antigen, we developed a novel approach to target PRAME using a chimeric antigen receptor (CAR) construct encoding a targeting domain based on T-cell receptor (TCR) mimic antibodies that target the peptide-HLA complex. We used the antibody sequence from a previously designed TCR mimic (mTCR) antibody, Pr20, that recognizes the PRAME ALY peptide in complex with HLA-A∗02 and verified expression of PRAME in AML cell lines and primary AML blasts. Using the Pr20 antibody sequence, we developed CAR T cells (PRAME mTCRCAR T) to be tested against primary samples from patients with AML and AML cell lines that express the PRAME antigen in the context of HLA-A2 expression. In contrast to appropriate controls, PRAME mTCRCAR T cells demonstrate target-specific and HLA-mediated in vitro activity in OCI-AML2 and THP-1 cell lines, HLA-A2 cell lines expressing the PRAME antigen, and against primary AML patient samples. In vivo cell-derived xenograft models treated with PRAME mTCRCAR T cells demonstrated potent leukemia clearance and improved survival compared with unmodified T-cell controls. Furthermore, the cytolytic activity of PRAME mTCRCAR T cells was enhanced by treating the target cells with interferon gamma, which increases PRAME antigen expression. These results demonstrate the feasibility and efficacy of targeting PRAME with novel PRAME mTCRCAR T cells.


Synthesis, Regulatory Factors, and Signaling Pathways of Estrogen in the Ovary.
New insights have been thrown for understanding the significant role of estrogen on various systems of humans. Increasing evidences have determined the significant roles of estrogen in female reproductive system. So, the normal synthesis and secretion of estrogen play important roles in maintaining the function of tissues and organs. The ovaries are the main synthetic organs of estrogen. In this review, we summarized the current knowledge of the estrogen synthesis in the ovaries. A series of factors and signaling pathways that regulate the synthesis of estrogen are expounded in detail. Understanding the regulating factors and potential mechanism related to estrogen synthesis will be beneficial for understanding estrogen disorder related diseases and may provide novel therapeutic targets.


Effect of NADPH oxidase inhibitor-apocynin on the expression of Src homology-2 domain-containing phosphatase-1 (SHP-1) exposed renal ischemia/reperfusion injury in rats.
This study was designed to evaluate whether NADPH oxidase inhibitor (apocynin) preconditioning induces expression of Src homology-2 domain-containing phosphatase-1 (SHP-1) to protect against renal ischemia/reperfusion (I/R) injury (RI/RI) in rats. Rats were pretreated with 50 mg/kg apocynin, then subjected to 45 min ischemia and 24 h reperfusion. The results indicated that apocynin preconditioning improved the recovery of renal function and nitroso-redox balance, reduced oxidative stress injury and inflammation damage, and upregulated expression of SHP-1 as compared to RI/RI group. Therefore our study demonstrated that apocynin preconditioning provided a protection to the kidney against I/R injury in rats partially through inducing expression of SHP-1.


Why mothers die at a busy tertiary urban hospital in Kampala, Uganda: a comprehensive review of maternal deaths 2016-2018 and implications for quality improvement to reduce deaths.
Reviewing maternal deaths and drawing out lessons for clinical practice is part of an effective cohesive intervention strategy to reduce future deaths. To review maternal deaths at the National Referral hospital in Kampala over a 3-year period (2016-2018) to determine causes of death, extent of preventability, proportion of deaths notified and audited as per national guidelines. Trained-multidisciplinary panels (obstetricians and senior midwives) conducted retrospective reviews of maternal deaths that occurred. Major causes of deaths: obstetric haemorrhage (158/350; 45%), hypertensive disorders of pregnancy (87/350; 25%) and infection (95/350; 27%). Overall, 294/350 (84%) of maternal deaths were considered preventable. In 95% (332/350) of cases, delays within healthcare facilities were identified (64%; 226/350). We note that only 115/350 (33%) cases had been audited. This proportion did not change during the studied period. In 48% (167/350) of cases, notification to the Ministry of Health occurred, but only 11% of deaths (39/350) were notified within the recommended 24-hours. A high proportion (84%) of deaths were preventable. Significant delays to care occurred within health-care facilities. Results suggest that a well-supported, and timely maternal death review process with targeted and pragmatic interventions might be effective in reducing maternal deaths in this setting.


Antigen-specific helper T cells recognize determinants encoded in the H-2D region of the H-2 gene complex.
Observations have frequently been interpreted as showing that the helper T cells which collaborate with alloantigen-specific cytotoxic T-cell precursors can only recognize antigens encoded in the I region of the H-2 gene complex. An experimental system is described here that allows analysis of the recognition repertoire of these helper cells. CBA helper T-cell precursors can be primed in vitro to antigens encoded in the H-2b gene complex. These helpers can then be tested for the existence of a subset of helper cells which recognize antigens encoded in the D region of H-2b haplotype. CBA thymocytes were used as a source of cytotoxic T-cell precursors that respond poorly in the absence of exogeneous helper activity. The source of alloantigen was varied by using irradiated spleen cells from various (BALB/c X recombinant)F1 hybrid mice as stimulator cells. When the stimulator cell bears BALB/c determinants recognized by the cytotoxic T-cell precursor and also bears only the D region antigens of the H-2b haplotype, an anti-BALB/c cytotoxic response is generated only if the anti-H-2b helper population contains cells able to recognize H-2Db. A positive cytotoxic response was obtained, indicating that helper cells are not limited to recognition of I region antigens and can efficiently recognize antigens encoded in the D region of the H-2 gene complex. This was confirmed by the demonstration of helpers specific for H-2Dd. We were unable to detect any evidence for Ia-restricted recognition of the H-2D alloantigens, suggesting that, as for cytotoxic T lymphocytes (CTL), helper cell recognition of class I alloantigens is an unrestricted event.


Presynaptic Mechanisms Mediating Retrograde Semaphorin Signals for Climbing Fiber Synapse Elimination During Postnatal Cerebellar Development.
Elimination of early-formed redundant synapses during postnatal development is essential for functional neural circuit formation. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs). During postnatal development, a single CF is selectively strengthened in each PC and becomes a "winner" CF that is presumed to remain into adulthood, whereas the other "loser" CFs are eliminated. These developmental changes are dependent on neural activity and signal cascades in postsynaptic PCs. Several molecules essential for CF synapse elimination have been identified in postsynaptic PCs. Importantly, we have recently uncovered that Semaphorin3A (Sema3A) and Semaphorin7A (Sema7A) derived from postsynaptic PCs act retrogradely onto presynaptic CFs and regulate CF synapse elimination. We demonstrate that Sema3A strengthens and maintains CF synapses from postnatal day 8 (P8) to P18 and opposes the force of CF elimination. In contrast, Sema7A facilitates elimination of weaker CFs from PC somata after P15. In the continuing studies, we searched for molecules that mediate these retrograde semaphorin signals in presynaptic CFs. This short article describes how Sema3A strengthens and maintains, whereas Sema7A promotes elimination of CF synapses through respective receptors and downstream molecules in presynaptic CFs during postnatal cerebellar development.


Intensive Interaction Training for Paid Carers: 'Looking, Looking and Find Out When They Want to Relate to You'.
Intensive interaction (II) is a communication approach useful for working with people with severe intellectual disabilities. Health and social care providers offer II training courses to paid carers working in local services with the goal of improving social communication for their clients. Eight paid carers who had been trained in II were interviewed 2-3 years after training, to explore how their practice had changed, and whether any changes were sustainable. Interviews were analysed using interpretative phenomenological analysis. Analysis revealed a master theme of emotional and practical endurance, with empowerment, better understanding and perceived barriers to implementation comprising subthemes. Despite actual and perceived barriers to the enduring use of II, all participants spoke positively of the approach and were continuing to use II in practice.


Hypotension and hypovolemia during hemodialysis: is the usual suspect innocent?
Hypotension during intermittent hemodialysis is common, and has been attributed to acute volume shifts, shifts in osmolarity, electrolyte imbalance, temperature changes, altered vasoregulation, and sheer hypovolemia. Although hypovolemia may intuitively seem a likely cause for hypotension in intensive care patients, its role in the pathogenesis of intradialytic hypotension may be overestimated.


Behavioral characteristics of WAG/Rij rats susceptible and non-susceptible to audiogenic seizures.
Some rats of the WAG/Rij (Wistar Albino Glaxo from Rijswijk) and Wistar strain are susceptible for audiogenic (convulsive) seizures. In the present study, behavior of susceptible and non-susceptible rats from the WAG/Rij strain, genetically predisposed to absence epilepsy, and outbred Wistar strain, genetically not predisposed to absence epilepsy, was compared to assess the level of anxiety (in the open field, light-dark choice and elevated plus-maze tests) and the level of depression (in the sucrose consumption and forced swimming tests). Increased level of anxiety was found only in audiogenic susceptible rats both from WAG/Rij and Wistar strain, but increased level of depression was found only in WAG/Rij rats independently of their susceptibility to audiogenic seizures. The results suggest that enhanced level of depression in WAG/Rij strain rats is associated with absence epilepsy but enhanced level of anxiety with susceptibility to audiogenic seizures.


Discordant vestibulo-ocular reflex function according to the frequency and mode of stimulation.
This study aimed to determine the incidence, pattern, and etiology of dissociated vestibulo-ocular reflex (VOR) function according to the stimulus frequency in dizzy patients. We retrospectively evaluated the results of bithermal caloric tests and video-head impulse tests (vHITs) in 1022 patients with dizziness or vertigo between July 2016 and April 2021. Patients were classified into concordant group (normal or abnormal results on both tests) and discordant group (dissociated results between two tests). Of 1022 patients, discordant group had 159 (16%), comprising abnormal horizontal vHITs with normal caloric responses (n = 36, 23%) and abnormal caloric tests with normal horizontal vHITs (n = 123, 77%). The former group showed similar frequency of peripheral (44%) and central (42%) causes, and more common involvement of bilateral horizontal semicircular canals in central than peripheral causes (86.7 vs 37.5%, p = 0.005). The most common peripheral causes were Meniere's disease and chronic vestibular neuritis, while central causes were variable, but mainly affecting the cerebellum. In the latter group, peripheral causes were common (67%), with the main etiologies being Meniere's disease and vestibular neuritis, whereas central causes were found in only 5%. The degree of canal paresis did not differ significantly between patients with central and peripheral causes. Discordant VOR function according to the stimulus frequency was not uncommon in dizzy patients. Specific patterns of VOR dissociation according to the disease etiologies may offer insight into underlying pathophysiology.


GenoType MTBDRplus Assay for Rapid Detection of Multidrug Resistance in Mycobacterium tuberculosis: A Meta-Analysis.
There is an urgent demand for rapid and accurate drug-susceptibility testing for the detection of multidrug-resistant tuberculosis. The GenoType MTBDRplus assay is a promising molecular kit designed for rapid identification of resistance to first-line anti-tuberculosis drugs, isoniazid and rifampicin. The aim of this meta-analysis was to evaluate the diagnostic accuracy of GenoType MTBDRplus in detecting drug resistance to isoniazid and rifampicin in comparison with the conventional drug susceptibility tests. We searched PubMed, EMBASE, and Cochrane Library databases to identify studies according to predetermined criteria. A total of 40 studies were included in the meta-analysis. QUADAS-2 was used to assess the quality of included studies with RevMan 5.2. STATA 13.0 software was used to analyze the tests for sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curves. Heterogeneity in accuracy measures was tested with Spearman correlation coefficient and Chi-square. Patient selection bias was observed in most studies. The pooled sensitivity (95% confidence intervals were 0.91 (0.88-0.94) for isoniazid, 0.96 (0.95-0.97) for rifampicin, and 0.91(0.86-0.94) for multidrug-resistance. The pooled specificity (95% CI) was 0.99 (0.98-0.99) for isoniazid, 0.98 (0.97-0.99) for rifampicin and 0.99 (0.99-1.00) for multidrug-resistance, respectively. The area under the summary receiver operating characteristic curves ranged from 0.99 to 1.00. This meta-analysis determined that GenoType MTBDRplus had good accuracy for rapid detection of drug resistance to isoniazid and/or rifampicin of M. tuberculosis. MTBDRplus method might be a good alternative to conventional drug susceptibility tests in clinical practice.


The reaction between nitracrine and glutathione: implications for hypoxic cell radiosensitization and cytotoxicity.
Nitracrine (NC) is an electron affinic DNA intercalating agent and a potent hypoxia-selective cytotoxin and radiosensitizer in cell culture. Although NC is too cytotoxic and too rapidly metabolized to provide hypoxic cell radiosensitization in tumors, it is of mechanistic interest as an example of a DNA affinic radiosensitizer. We have observed a rapid chemical reaction between NC and reduced glutathione (GSH), which suggests that the observed potent in vitro cytotoxicity and radiosensitization might be dependent on thiol depletion by the large extracellular reservoir of drug. However, no GSH depletion was observed under conditions providing radiosensitization or rapid cell killing, and prior depletion of GSH by buthionine sulphoximine had no effect on cytotoxicity or formation of macromolecular adducts. Further, the intracellular reaction of NC with GSH is slower than predicted on the basis of the measured second order rate constant and the total intracellular concentrations of both species. The results are consistent with a role for DNA binding in protecting NC from reaction with GSH, and in improving the efficiency with which reduced electrophilic metabolites react with DNA in preference to GSH.


Type-1 steroid 5 alpha-reductase is functionally active in the hair follicle as evidenced by new selective inhibitors of either type-1 or type-2 human steroid 5 alpha-reductase.
Steroid 5 alpha-reductase catalyzes the reduction of testosterone (T) into the very potent androgen dihydrotestosterone (DHT). The different tissue expression patterns of the two isoforms of 5 alpha-reductase, namely type-1 and type-2 5 alpha-reductase (5 alpha-R1 and 5 alpha-R2, respectively), have prompted studies directed towards the synthesis of selective 5 alpha-R1 or 5 alpha-R2 inhibitors. In this present work, we have performed a structure/activity study on the inhibitory potential of indole carboxylic acids against hair follicle 5 alpha-reductase activity. We have demonstrated that this class of molecules were potent inhibitors of either 5 alpha-R1 or 5 alpha-R2 or both depending on (i) substituents in positions 4, 5 or 6 and (ii) the presence of a free carboxylic group. We have also found that only 5 alpha-R1 or 5 alpha-R1/R2 inhibitors were able to inhibit 5 alpha-reductase activity in plucked hairs from female volunteers or in freshly isolated female hair follicles, selective 5 alpha-R2 inhibitors being inactive.


Prophylactic epinephrine attenuates severe bleeding in lung transplantation patients undergoing transbronchial lung biopsy: Results of the PROPHET randomized trial.
Severe hemorrhage is an uncommon yet potentially life-threatening complication of transbronchial lung biopsy. Lung transplantation recipients undergo multiple bronchoscopies with biopsy and are considered to be at an increased risk for bleeding from transbronchial biopsy, independent of traditional risk factors. We aimed to evaluate the efficacy and safety of endobronchial administration of prophylactic topical epinephrine in attenuating transbronchial biopsy-related hemorrhage in lung transplant recipients. The Prophylactic Epinephrine for the Prevention of Transbronchial Lung Biopsy-related Bleeding in Lung Transplant Recipients study was a 2-center, randomized, double blind, placebo-controlled clinical trial. Participants undergoing transbronchial lung biopsy were randomized to receive 1:10,000-diluted topical epinephrine vs saline placebo administered prophylactically into the target segmental airway. Bleeding was graded based on a clinical severity scale. The primary efficacy outcome was incidence of severe or very severe hemorrhage. The primary safety outcome was a composite of 3-hours all-cause mortality and an acute cardiovascular event. A total of 66 lung transplantation recipients underwent 100 bronchoscopies during the study period. The primary outcome of severe or very severe hemorrhage occurred in 4 cases (8%) in the prophylactic epinephrine group and in 13 cases (24%) in the control group (p = 0.04). The composite primary safety outcome did not occur in any of the study groups. In lung transplantation recipients undergoing transbronchial lung biopsy, prophylactic administration of 1:10,000-diluted topical epinephrine into the target segmental airway before biopsy attenuates the incidence of significant endobronchial hemorrhage without conveying a significant cardiovascular risk. (ClinicalTrials.gov identifier: NCT03126968).


Sexually transmitted organisms in sexually abused children.
To establish the prevalence of sexually transmitted organisms and other genital organisms in potentially sexually abused children. Prospective study of children attending an inner London department of community paediatrics for evaluation of possible sexual abuse. Children under 16 referred for evaluation of possible sexual abuse. Prevalence of sexually transmitted organisms in relation to age, symptoms, and type of abuse. Swabs were taken from 159 of 242 girls evaluated. The overall prevalence of sexually transmitted organisms was 3.7%: three girls were infected with gonorrhoea, four with Trichomonas vaginalis, and two with Chlamydia trachomatis. One girl had all three infections plus mycoplasmas. Mycoplasmas were identified in 22% of girls swabbed. Of 30 boys swabbed, none yielded a sexually transmitted organism. There is a low prevalence of definitely sexually transmitted organisms in children who might have been abused. Other organisms possibly associated with sexual activity can be identified in this population. Screening for infection should be mandatory in presumed sexually abused girls with vaginal discharge and ideally should be undertaken in all children attending for evaluation of sexual abuse.


Comparative analysis of aroma compounds in French fries and palm oil at three crucial stages by GC/MS-olfactometry, odor activity values, and aroma recombination.
Flavor is a key element affecting the popularity of French fries (FFs). When oil is heated, the changes in oil quality can affect the flavor of the food directly. The flavor of FFs showed three crucial stages: the break-in (3.0% to 6.8% of total polar compounds (TPC)), optimum (7.0% to 19% of TPC), and degrading (above 19.5% of TPC) stages. To distinguish the key aroma compounds in the three stages, the FFs, prepared in palm oil (PO) at TPC of 3.0% (FF3), 7.5% (FF8), 19.5% (FF20), and their relevant oils (PO3, PO8, PO20), were selected for molecular sensory science analysis. The results indicated that the concentration of (E, E)-2,4-decadienal linked with the deep-fried odor was low in FF3, which led to a lower sensory score in the FF3 sample. The FF8 sample had a high (E, E)-2,4-decadienal content and received a high sensory score. The FF20 sample possessed high hexanoic acid, heptanoic acid (sweaty odor), benzaldehyde (stale odor), octanoic acid (sweaty odor), (E)-2-undecenal (fatty odor), and trans-4,5-epoxy-(E)-2-decenal (metallic odor) content, thus leading to FFs having an undesirable flavor and PO20 showed high hexanoic acid and heptanoic acid content, contributing to a lower sensory score in PO20. The FFs' flavor became undesirable when TPC was above 19.5% due to significant influences of some off-flavor compounds. It is therefore essential to prevent the generation of rancid substances to prolong the optimum stage during frying. © 2021 Society of Chemical Industry.


[Practical Year - Surgery in the Reformed Curriculum MaReCuM (Mannheim)].
Background: Since 2006 the practical year in the Mannheim Reformed Curriculum Medicine (MaReCuM) is divided into four quarters: the two required subjects (surgery and internal medicine), one elective and one of four offered fields in ambulatory medicine. Therefore students can more intensively focus on their preferences in the practical year. In the present article we describe the provided surgical training sites, the organisation of the practical year, the surgical training itself and the quality management. We provide answers to the following questions: does dividing the practical year into quarters have a (negative) influence on the grades of final exams; how interested, motivated and satisfied are students in the different (surgical) quarters of the practical year and in which quarter(s) can new generation staff be recruited? Methods: We used results of the final exams of three cohorts of the traditional Mannheim track and three cohorts of MaReCuM, as well as the results of the Mannheim Questionnaire of Satisfaction with Training Conditions in the Practical Year of Medical Education from the regular evaluation of three practical year cohorts within two years. Conclusions: Dividing the practical year into quarters is possible and can be organised together with the new "mandatory subject" ambulatory medicine. The introduction of quarters has no negative effects on the results of final exams. The assignment in the surgical field from students' perspectives with regard to motivation, interest, knowledge and satisfaction with training is comparable to surgical electives. Therefore recruitment of new staff is possible either in the surgical elective or in the surgical area of ambulatory medicine.


Impact of cibenzoline treatment on left ventricular remodelling and prognosis in hypertrophic obstructive cardiomyopathy.
This study aimed to elucidate the long-term effect of cibenzoline therapy on cardiovascular complications and prognosis in patients with hypertrophic obstructive cardiomyopathy (HOCM). Eighty-eight patients with HOCM were treated with cibenzoline (Group A), and 41 patients did not receive cibenzoline (Group B). The changes in left ventricular (LV) remodelling, incidences of cardiovascular complications and deaths, were examined. The mean follow-up period was 15.8 ± 5.6 years in Group A and 17.8 ± 7.2 years in Group B. In Group A, the LV pressure gradient (LVPG) decreased immediately after treatment, and the reduction was maintained throughout the study. In Group B, the LVPG decreased gradually according to the deterioration of LV function. LV reverse remodelling was confirmed in Group A, and LV remodelling advanced in Group B. In Group A, the incidence of each cardiovascular complication was <10%. Only one patient experienced LV heart failure (LVHF). LVHF incidence and atrial fibrillation were higher in Group B than those in Group A (P < 0.0001). The incidence of death was 20.5% in Group A and 90.2% in Group B (P < 0.0001). The most frequent cause of death was sudden cardiac death (SCD) (38.9%) in Group A and LVHF (67.6%) in Group B. The incidence of SCD showed no significant difference between the two groups. The cumulative cardiac survival rate was higher in Group A than that in Group B (P < 0.0001). Cibenzoline treatment significantly reduced all cardiovascular complications and death due to LVHF and may be a promising treatment in patients with HOCM.


Use of neuromelanin-sensitive MRI to distinguish schizophrenic and depressive patients and healthy individuals based on signal alterations in the substantia nigra and locus ceruleus.
We investigated alterations in the substantia nigra pars compacta (SNc) and locus ceruleus (LC) in schizophrenic and depressive patients by using a neuromelanin-sensitive magnetic resonance imaging (MRI) technique that enables direct visualization of these nuclei and examined whether this technique could distinguish between these disorders and healthy subjects. Using a neuromelanin-sensitive T1-weighted MRI technique, we examined 20 schizophrenia patients, 18 depressive patients, and 34 healthy control subjects. The signal intensities of the areas corresponding to the SNc and LC were measured, and the contrast ratios (CR) to the adjacent white matter were calculated. The CR of the SNc was significantly higher in schizophrenic patients (22.6 +/- 5.6) than in depressive patients (19.2 +/- 4.7) and healthy control subjects (19.6 +/- 3.8), whereas the CR of the LC in depressive patients (7.7 +/- 2.4) was significantly lower than that in healthy control subjects (11.0 +/- 3.9) and schizophrenic patients (10.0 +/- 3.1). Further, the difference in the CR between the SNc and LC was significantly greater in schizophrenic patients (12.6 +/- 6.7) than in control subjects (8.6 +/- 4.1). Neuromelanin-sensitive MRI enables visualization of alterations in the SNc and LC that are observed in schizophrenia and depression.


[Role of angiotensin II in elaborating the escape reaction during electric stimulation of the ventromedial hypothalamus in rabbits].
The action of angiotensin-II, saralazin, captopril and antiserum to angiotensin-II, injected into the brain ventricles, on avoidance reaction to electrical stimulation of ventromedial hypothalamus was studied in experiments on rabbits. It has been found that angiotensin-II had a pronounced inhibitory effect, while saralazin, captopril and antiserum to angiotensin-II had a facilitating effect on the reaction.


Synthesis and Evaluation of a Rationally Designed Click-Based Library for G-Quadruplex Selective DNA Photocleavage.
DNA containing repeating G-rich sequences can adopt higher-order structures known as G-quadruplexes (G4). These structures are believed to form within telomeres and the promoter regions of some genes, particularly in a number of proto-oncogenes, where they may play a role in regulating transcription. Alternatively, G4 DNA may act as a barrier to replication. To investigate these potential biological roles, probes that combine highly selective G4 DNA targeting with photocleavage activity can allow temporal detection of G4 DNA, providing opportunities to obtain novel insights about the biological roles of G4 DNA. We have designed, synthesized, and screened a small library of potential selective G-quadruplex DNA photocleavage agents incorporating the G-quadruplex targeting moiety of 360A with known photocleavage groups linked via "click" chemistry.


Does urinary incontinence occurrence depend on the menstrual cycle phase?
The aim was to study an eventual co-variation of menstrual cycle progression and urinary incontinence (UI) occurrence in 20-54-year-old-women, who have regular menstrual cycles, which are not influenced by exogenous sex hormones. An age-stratified random sample of of 3900 women, aged 20-59 years, answered a questionnaire on UI. The present analysis included 821 women, who reported regular menstrual cycles un-intervened by sex hormone intake. Five percent of the women reported episodes of UI the day before they answered the questionnaire. Urinary incontinence was unassociated with menstrual cycle characteristics, such as time position from day one in the menstrual cycle, presence and amount of bleeding and the number of sanitary towels or tampons used. There was however, a borderline significant association (P = 0.08) with day 11-15 before the expected next menstrual bleeding. The present data allow for limited co-variation, if any, to exist in UI occurrence with the natural menstrual cycle phases, including the menstruation itself. A hypothesis of a moderate UI increase associated with ovulation however, merits attention.


Purification and partial characterization of the myelin-associated glycoprotein from adult rat brain.
The myelin-associated glycoprotein was purified from rat central nervous system myelin by selective extraction with lithium diiodosalicylate-phenol followed by gel filtration on a column of Sepharose CL-6B. Amino acid analysis of the purified glycoprotein revealed an excess of acidic over basic amino acids and a relatively high content of nonpolar residues. On the basis of weight, the molecule is about one-third carbohydrate consisting of 5% fucose, 23% mannose, 20% galactose, 34% N-acetylglucosamine, and 18% N-acetylneuraminic acid.


Comparison between mitomycin C and chitosan for prevention of anterior glottic steno after CO2 laser cordectomy in dogs.
To compare the effectiveness of an immediate application of topical mitomycin C (MMC) with chitosan for prevention of anterior glottic stenosis (AGS) after microsurgical resecting of both vocal fold with CO2 laser, including the anterior commissure, in a canine model. Prospective randomized experimental study. Twenty-four canine larynges were injured by a microresecting procedure of both vocal folds with a CO2 laser. The dogs were randomly divided into three groups for treatment, respectively with MMC, chitosan, or isotonic sodium chloride solution (control) for 5 minutes immediately after surgery. One week after the initial surgery, three dogs in each group were randomly selected, the ultrastructures of the fibroblasts were examined with a transmission electronic microscope, and expression of basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1) were evaluated by enzyme-linked immunosorbent assay (ELISA). Three weeks after surgery, the remaining dogs' glottic web were lysed and repeatedly treated with MMC, chitosan, or isotonic sodium chloride solution. The glottic wound healing and AGS formation were examined every week, and all larynges were harvested and examined histologically 6 weeks after the initial surgery. Results included 1) transmission electronic microscope examination of the ultrastructures of the fibroblasts indicated that both MMC and chitosan inhibited the proliferation of fibroblast; 2) the expression of bFGF and TGF-beta1 increased both in the MMC group and the chitosan group, and the expression of bFGF in the chi-tosan group was higher than in the MMC group (P = .010), while the expression of TGF-beta1 was lower (P = .000);3) the extent of AGS formation was decreased both in the MMC group and the chitosan group, while it was less in the chitosan group than in the MMC group (P = .047); 4) the grade of collagen content between the MMC group and the chitosan group was not significantly different (P = .5). Chitosan is more effective in preventing AGS after CO2 laser cordectomy than MMC.


Are conventional reconstruction plates equivalent to precontoured locking plates for distal humerus fracture fixation? A biomechanics cadaver study.
The optimal plate type and configuration for distal humerus fracture fixation has yet to be defined. Available biomechanical studies show conflicting results. No existing studies compare conventional reconstruction plates to newer precontoured distal humerus locking plates in both parallel and perpendicular configurations. Three groups of humerus specimens were compared via biomechanical testing in a cadaver model simulating metaphyseal comminution. Group 1 consisted of conventional reconstruction plates in a perpendicular configuration. Group 2 used precontoured locking plates in a perpendicular configuration. Group 3 used precontoured locking plates in a parallel configuration. Each group was tested for stiffness in anterior bending, posterior bending, axial compression, and torsion. The specimens then underwent cyclic loading followed by single load to failure in posterior bending. There was no significant difference between the three groups for anterior bending, posterior bending, axial compression, or torsional stiffness. There was no significant difference in load to failure for any of the three groups. Screw loosening was significantly higher in Group 1 when compared to Groups 2 and 3 after cyclic loading. In the early postoperative period, less expensive perpendicular conventional reconstruction plate constructs provide similar stiffness and load to failure properties to newer precontoured locking plate systems regardless of plate configuration.


Calcium-activated outward current in voltage-clamped hippocampal neurones of the guinea-pig.
Slow clamp currents were recorded from CA1 and CA3 pyramidal neurones in slices of guinea-pig hippocampus maintained in vitro, using a single micro-electrode sample-and-hold technique. Depolarizing voltage commands evoked a time- and voltage-dependent outward current which was suppressed by removing external Ca or by adding Cd (0.5 mM) or Mn (5 mM). This Ca-dependent current (Ic) was not reduced by muscarinic agonists (unlike IM) but was greatly reduced by 5-20 mM-tetraethylammonium (TEA). Repolarizing IC tail currents reversed at -73 +/- 5 mV in 3 mM-K solution. The reversal potential became about 30 mV more positive on raising [K]o to 15 mM. No clear change in current amplitude or tail-current reversal potential occurred on adding Cs (2 mM), reducing [Cl]o from 128 to 10 mM, or replacing external Na with Tris. The underlying conductance GC was activated at membrane potentials positive to -45 mV. At -32 mV GC showed an approximately exponential increase with time, with a time constant of approximately 0.6 sec at 26 degrees C. Repolarizing tail currents declined exponentially with time, the time constant becoming shorter with increasing negative post-pulse potentials. When the clamp was switched off at the end of a depolarizing command of sufficient amplitude and duration to activate IC, a membrane hyperpolarization to -73 mV ensued, of similar amplitude and decay time to that following spontaneous action potentials. It is concluded that the clamp current observed in these experiments is probably the Ca-activated K current thought to contribute to the post-activation after-hyperpolarization in hippocampal neurones.


Vehicle operating speeds in southwestern Colombia: An important database for the future implementation of optimization models for geometric design of roads in mountain topography.
The essential objective of a road is framed in allowing the circulation of vehicles from a point of origin to a destination, being essential to fulfil completely this function, consider aspects such as: functionality, safety, economy, comfort, environmental integration and harmony or aesthetics. For this effect, a geometric design based on consistency must be achieved, which arranges the elements of the road and their geometric characteristics, helping to minimize adverse effects on the driver's expectations, perceiving homogeneity on the route, without abrupt variation in the level of attention necessary and thus be able to adapt to the changing geometric conditions of the road. In order to assess the consistency in the geometric design, different criteria and methodologies strongly related to the level of accident rates have been developed, which in turn are based on the analysis of the evolutions of the operating speeds. By virtue of the above, speed is therefore of vital importance to carry out any type of evaluation or analysis of traffic, since it is an important indicator of the quality of the service offered to users, because of it is function of the physical characteristics of the road and its environment. Among the main characteristics of vehicular traffic that can be studied from speed data, we have: the intensity of circulation, vehicle speeds and travel time, origin and destination of trips, vehicular accidents, among others. The purpose of this document is to present a database of speed obtained on a road located in the Pasto (Nariño department) in southwestern Colombia. The analysed road sector has a total length of 27.5 km and is developed in a predominantly mountainous topography. The data collected corresponds to the geometric characteristics of the road, as well as the design, traffic and operating speeds of each element throughout the sector. The data series corresponds to 312 elements of the geometric design, which are located continuously along sector. The design and road speed for each element, was determined from the geometric characteristics of the road; meanwhile, the operating speed was determined using spot speed data, which was obtained from field measurements with the Bushnell Radar Gun. For the determination of the Operating Speed in each element of the layout and for each class of vehicle considered (cars, buses and two-axle trucks), in each direction of movement, a minimum sample size of 64 Spot Speed data was used. The speed dataset is of great importance, because it provides traffic and transport engineering with relevant information for investigations such as: analysis of traffic accidents, establishment of design elements, traffic operation plans, regulation and control, zones with speed problems, study of traffic flows and finally, the assignment of design speeds for similar and future projects.


Temporal assessment of bone marrow lesions on magnetic resonance imaging in a canine model of knee osteoarthritis: impact of sequence selection.
To assess the evolution of bone marrow lesions (BMLs) in a canine model of knee osteoarthritis (OA) using three different magnetic resonance imaging (MRI) sequences. Three MRI sequences [coronal, T1-weighted three-dimensional fast gradient recalled echo (T1-GRE), sagittal fat-suppressed 3D spoiled gradient echo at a steady state (SPGR), and sagittal T2-weighted fast spin echo with fat saturation (T2-FS)] were performed at baseline, and at week 4, 8 and 26 in five dogs following transection of the anterior cruciate ligament. The same reader scored (0-3) subchondral BMLs twice, in blinded conditions, according to their extent in nine joint subregions, for all imaging sessions, and independently on the three MRI sequences. Correlation coefficients and Bland-Altman plots evaluated intra-reader repeatability. Readings scores were averaged and the nine subregions were summed to generate global BML scores. BMLs were most prevalent in the central and medial portions of the tibial plateau. Intra-reader repeatability was good to excellent for each sequence (r(s)=0.87-0.97; P<0.001). Maximal intra-reader variability (24%) was reached on T2-FS and was associated to higher scores (P<0.05). Global BML scores increased similarly on all three sequences until week 8 (P<0.05). At week 26, score on T2-FS was decreased, being lower when compared to T1-GRE and SPGR (P<0.05). In this canine OA model, the extent of BMLs varies in time on different MRI sequences. Until the complex nature of these lesions is fully resolved, it is suggested that to accurately assess the size and extent of BMLs, a combination of different sequences should be used.


The effect of face mask wearing on language processing and emotion recognition in young children.
Face mask wearing was an important preventative strategy for the transmission of the COVID-19 virus. However, the effects that occluding the mouth and nose area with surgical masks could have on young children's language processing and emotion recognition skills have received little investigation. To evaluate the possible effects, the current study recruited a sample of 74 children from the North West of England (aged 4-8 years). They completed two computer-based tasks with adults wearing or not wearing surgical face masks to assess (a) language processing skills and (b) emotion recognition ability. To control for individual differences, age, sex, receptive vocabulary, early reading skills, and parent-reported social-emotional competence were included in analyses. The findings from the study highlighted that although younger children were less accurate than older children, face masks did not significantly impair basic language processing ability. However, they had a significant effect on the children's emotion recognition accuracy-with masked angry faces more easily recognized and masked happy and sad faces less easily recognized. Children's age and social-emotional skills also played a role. The findings suggest that the effects of face masks should continue to be evaluated.


Two new cytotoxic monotetrahydrofuran Annonaceous acetogenins, annomuricins A and B, from the leaves of Annona muricata.
The leaves of Annona muricata have yielded eight monotetrahydrofuran Annonaceous acetogenins. Two of them, annomuricins A [1] and B [2], whose chemical structures were deduced by ms, nmr, ir, and uv spectral and chemical methods, are novel and unusual. Compounds 1 and 2 each possess five hydroxyl groups; two hydroxyl groups are vicinal, with the vicinal group of 1 threo and that of 2 erythro. The absolute configurations of 1 and 2 were determined by Mosher ester methodology. Six monotetrahydrofuran acetogenins, previously described in the seeds, were found in the leaves; these are gigantetrocin A, annonacin-10-one, muricatetrocins A and B, annonacin, and goniothalamicin.


Melatonin blunted the angiogenic activity in 3D colon cancer tumoroids by the reduction of endocan.
Complexity and heterogeneity of the tumor niche are closely associated with the failure of therapeutic protocols. Unfortunately, most data have been obtained from conventional 2D culture systems which are not completely comparable to in vivo microenvironments. Reconstructed 3D cultures composed of multiple cells are valid cell-based tumor models to recapitulate in vivo-like interaction between the cancer cells and stromal cells and the oncostatic properties of therapeutics. Here, we aimed to assess the tumoricidal properties of melatonin on close-to-real colon cancer tumoroids in in vitro conditions. Using the hanging drop method, colon cancer tumoroids composed of three cell lines, including adenocarcinoma HT-29 cells, fibroblasts (HFFF2), and endothelial cells (HUVECs) at a ratio of 2: 1: 1, respectively were developed using 2.5% methylcellulose. Tumoroids were exposed to different concentrations of melatonin, from 0.005 to 0.8 mM and 4 to 10 mM, for 48 h. The survival rate was measured by MTT and LDH leakage assays. Protein levels of endocan and VEGF were assessed using western blotting. Using histological examination (H & E) staining, the integrity of cells within the tumoroid parenchyma was monitored. Despite the reduction of viability rate in lower doses, the structure of tumoroids remained unchanged. In contrast, treatment of tumoroids with higher doses of melatonin, 4 and 10 mM, led to disaggregation of cells and reduction of tumoroid diameter compared to the non-treated control tumoroids (p < 0.05). By increasing melatonin concentration from 4 to 10 mM, the number of necrotic cells increased. Data showed the significant suppression of endocan in melatonin-treated tumoroids related to the non-treated controls (p < 0.05). According to our data, melatonin in higher doses did not alter protein levels of VEGF (p > 0.05). Melatonin can exert its tumoricidal properties on colon cancer tumoroids via the reduction of tumor cell viability and inhibition of the specific pro-angiogenesis factor.


High rate of severe fetal outcomes associated with maternal parvovirus b19 infection in pregnancy.
To augment the understanding of parvovirus B19 infection in pregnancy with respect to maternal characteristics and their corresponding fetal outcomes. Retrospective case-series of all women referred to Magee-Women_s Hospital with serologically-documented parvovirus B19 infection during pregnancy from 1998-2001. All 25 cases that are available for analysis occurred from January through June. The frequency of cases varied substantially from year to year, with 14 cases in 1998, 0 cases in 1999 and 2000, and 11 cases in 2001. In contrast to previous reports, the minority of women [4/25(16%)] experienced symptoms attributable to parvovirus B-19 infection although 3 of 25 (12%) fetuses developed hydrops fetalis and 4/25 (16%) suffered an intrauterine of fetal death. These findings suggest that parvovirus B19 infection in pregnancy follows seasonal and annual trend variation, may produce a lower frequency of maternal symptoms and a higher fetal loss rate than previously reported. Synopsis. Maternal parvovirus B19 infection follows seasonal and annual variation is often asymptomatic and may have higher fetal loss rates than previously reported. Continued surveillance is warranted.


Decreased Expression of Thyroglobulin and Sodium Iodide Symporter Genes in Hashimoto's Thyroiditis.
Aim. The aim of the study was to compare the expression of sodium iodide symporter (NIS), thyroglobulin (Tg), tumor necrosis factor- α (TNF α ), and interleukin-1 β genes in patients with Hashimoto's thyroiditis (HT) and healthy individuals. Subjects and Methods. Thyroid cells were obtained from 39 patients with HT and 15 controls by an ultrasound guided fine needle aspiration biopsy. Results. The patients with HT had lower Tg and NIS mRNA (P = 0.002 and P = 0.001, resp.), as well as higher TNF α mRNA expression (P = 0.049) than the controls. In the HT group Tg mRNA expression correlated positively with NIS mRNA expression (R = 0.739, P = 0.0001) and thyroid volume (R = 0.465, P = 0.0005), as well as negatively with TNF α mRNA expression (R = -0.490, P = 0.001) and anti-peroxidase antibodies (TPOAb) level (R = -0.482, P = 0.0002), whereas NIS mRNA expression correlated positively with thyroid volume (R = 0.319, P = 0.02), as well as negatively with TNF α mRNA expression (R = -0.529, P = 0.0006) and TPOAb level (R = -0.422, P = 0.001). Conclusions. Our results suggest that decreased Tg and NIS expression in thyroid cells may result in reduced active iodide transport and reduced thyroid volume in patients with HT.


Medico-legal implications of the fetal inflammatory response syndrome.
Babies who sustain long term neurologic injury and disability are frequent subjects in medical malpractice litigation. In the United States, the tort system enables adjudication of claims through a proscribed system. This paper will review salient elements of the tort system-duty, breach, causation, and damages- and how they apply to encephalopathic infants whose injuries are believed to be the result of fetal inflammatory response syndrome (FIRS) and/or hypoxic-ischemic damage. FIRS may confound the diagnosis of neonatal encephalopathy but may be a credible explanation for it as well. The ways in which FIRS may impact malpractice lawsuits are presented.