Viable deletion mutants in the simian virus 40 early region.
For the purpose of isolating hr-t-like mutants of simian virus 40, we have constructed variants that have lost the unique site for the restriction enzyme Taq I at 0.565. Five mutants have been isolated and characterized by restriction enzyme analysis. All of them produce a normal size T antigen. Four produce a t antigen reduced in size as well as in amount; the fifth one does not seem to make any t antigen at all. The ability of these mutants to transform mouse cells in vitro, as tested by anchorage dependence, is clearly altered; however, the defect is only partial. In the same test, the mutants can complement a tsA mutant for transformation and therefore define a second complementation group in the simian virus 40 early region.


Cerebral pattern of pro- and anti-inflammatory cytokines in dementias.
The knowledge regarding putative inflammatory component(s) participating in Alzheimer's disease (AD) and vascular dementia (VAD) is scarce. Recently, we have demonstrated the presence of certain inflammatory cytokines in the cerebrospinal fluid (CSF) of demented patients. Although the initial event(s) triggering the neurodegenerative processes in AD versus VAD may be different and lead to different neuropathological changes, it may initiate a similar cascade of cytokine production in response to neuronal injury. The cytokines released in the central nervous system (CNS) may, in turn, act in a similar manner in both diseases, amplifying some pathological changes such as amyloidogenesis and white matter lesions or on the contrary acting as neuroprotective molecules. This review will focus on the intracerebral production of the pro- and anti-inflammatory cytokines interleukin IL-1beta, IL-1 receptor antagonist (IL-1ra), IL-6 and TNF-alpha in dementia, and their relation to gene polymorphism, to cerebral neuronal damage, apoptosis, and to clinical variables of dementia. Our results, which show for the first time strikingly increased CSF levels of TNF-alpha but not of TNF-beta, IL-1beta or IL-6 in AD and VAD, may form a conceptual framework for further studies of neuroprotective mechanisms in dementias.


Comparison of different sampling methods for the determination of low-level radionuclides in air.
The aim of this work is to check the consistency of results given by different air dust samplers (flow-rates between 2 and 700m(3)/h) and measurement protocols at a single location. The study is focussed on (210)Pb since is the only nuclide that can be easily assessed through all the studied sampler types. Results from high- and mid-volume samplers agreed well to within the associated uncertainties. Gross beta activity from low-volume samplers can be used as a good indicator of the evolution of (210)Pb concentration in air.


Glycohemoglobin (Hb A1) levels in oral contraceptive users.
In a group of 33 healthy women, among whom 15 utilized the combined oral contraceptive pill, and 18 utilized the progesterone oral pill (ethynodiol diacetate, 0.5 mg, Femulen, we have examined the percentage of glycohemoglobin (Hb A1). In the progesterone oral pill users the percentage of Hb A1 remained unchanged, that is 5.4% before, and 5.2% 3-6 mth after using it, whereas in women taking the combined oral contraceptive pill the values increased from 5.9% before to a mean of 8.7% after 3-6 mth after administration. This increase seems to be related to the estrogen of the which, as in pregnancy, may induce glucose intolerance. From this study it may be seen that, despite its disadvantages such as reduced effectiveness and menstrual disruption, the progesterone-only pill is preferable. At the same time, the screening by the Hb A1 evaluation, a sure, inexpensive and easily performed procedure, makes it possible to detect a nonsuspected diabetes or a borderline diabetes and thus to change the contraception method used for another method.


Fixation Principles for Pathologic Fractures in Metasatic Disease.
The management of pathologic fractures differs from nonpathologic fractures with respect to preoperative evaluation, surgical strategies, adjuvant therapies, and complication rates. These issues must be understood to provide appropriate musculoskeletal care for patients with metastatic disease.


The relationship between radiation response of human squamous carcinoma cells and specific metabolic changes induced by chronic hypoxia.
Chronic hypoxia can cause a range of metabolic changes within cells, such as increasing the synthesis rate of a group of proteins, oxygen regulated proteins (ORPs) and reducing glutathione (GSH) content. We are currently interested in the radiation responses of cells during recovery after chronic hypoxia in relation to these metabolic changes. Experiments have therefore been carried out on the influence of hypoxic pretreatment to gamma rays of two human squamous carcinoma cell lines, A431 (vulva) and CaSki (cervix), in exponential and plateau growth phases. In both cell lines, the synthesis rate of ORPs reached to a maximum level after 12 hr of hypoxia and during the same time, the cellular GSH content reduced by about 50%, but both returned to the control levels by 12 hr of reoxygenation. After 12 hr of hypoxic incubation at 37 degrees C, cells were allowed to reoxygenate in air for 10 min (on ice) or 12 hr at 37 degrees C before irradiation. Clonogenic assays were performed immediately after irradiation. Compared to the aerobic control, the radiosensitivity of both cell lines reoxygenated for 10 min after hypoxia increased significantly and later returned to the aerobic control level by 12 hr of reoxygenation. Since aerobic A431 cells treated with 10 mM buthionine sulfoximine for 12 hr did not increase the radiosensitivity, the enhanced aerobic radiosensitivity observed after chronic hypoxia was unlikely to be directly related to decreased GSH content. Further investigations of ORPs and other associated metabolic changes caused by chronic hypoxia have been in progress to determine their possible role in this enhanced radiation sensitivity.


A cytotoxic anti-HLA-AB monoclonal antibody which in dilution becomes specific to HLA-A3 crossreacting group.
XI 20.4 monoclonal antibody belongs to the IgM class. It precipitates two polypeptide chains characteristic of HLA Class I antigens. At the highest dilutions it is cytotoxic against lymphocytes carrying antigens of the HLA-A3 crossreacting group. Lysostrip experiments show that, at the lowest dilutions, the antibody reacts either with HLA-A, or B antigens.


Treatment options for the free end saddle.
Many treatment options are available for the management of the free end saddle. This paper reviews past and current treatment methods for management of this situation. To understand the problem posed by the free end saddle and the techniques available to clinicians for its management in general dental practice.


Use of three-dimensional (3D) optical flow method in mapping 3D anatomic structure and tumor contours across four-dimensional computed tomography data.
A 3-dimensional (3D) optical flow program that includes a multi-resolution feature has been developed and applied to 3D anatomical structure and gross tumor volume (GTV) contour mapping for 4-dimensional (4D) CT data. The study includes contour mapping for 3 real patient CT data sets, and also for a thoracic phantom in which the displacement for each voxel is known. Of the real patient CT data sets, one set has been used to map contours of lung and GTV over all the respiration phases, while the others were studied using only the end inspiration and end expiration phases, in which the displacement between the phases were the largest. Including the residual motion in the 4D CT data and motion table shaking, the optical flow calculation agrees to within 1 mm with the known displacement. Excluding those errors that are not introduced by optical flow algorithm, the agreement can be within 0.1 mm with a displacement magnitude of 24 mm. The mapped contours of lungs, liver, esophagus, GTV, etc. in real patient 4D CT images were acceptable to clinicians. The 3D optical flow program is a good tool for anatomical structure and tumor volume contour mapping across 4D CT scans.


The effects of age and viral serology on γδ T-cell numbers and exercise responsiveness in humans.
γδ T-cells are cytotoxic effector cells that preferentially migrate to peripheral tissues and recognize many types of antigen. We examined the effects of age and viral serology on the exercise responsiveness of γδ T-cells. Blood was collected from 17 younger (age: 23-35yrs) and 17 older (50-64yrs) healthy males matched for cytomegalovirus (CMV), Epstein-Barr virus, herpes simplex virus-1 and Parvovirus B19 serologic status before and after a single bout of cycling exercise. Older had lower numbers and proportions of γδ T-cells than younger, while CMV was associated with increased numbers and proportions of γδ T-cells in younger but not older. Exercise evoked a ∼2-fold increase in circulating γδ T-cell numbers. The magnitude of this response was 3-times greater in younger compared to older, and 1.6-times greater in younger CMV-infected compared to younger non CMV-infected. To conclude, γδ T-cell numbers and exercise responsiveness decreases with age and may contribute to impaired immunosurveillance after acute acute physical stress.


The difference between shorter- versus longer-term psychotherapy for adult mental health disorders: a systematic review with meta-analysis.
The optimal psychotherapy duration for mental health disorders is unclear. Our aim was to assess the beneficial and harmful effects of shorter- versus longer-term psychotherapy for adult mental health disorders. We searched relevant databases and websites for published and unpublished randomised clinical trials assessing different durations of the same psychotherapy type before June 27, 2022. Our methodology was based on Cochrane and an eight-step procedure. Primary outcomes were quality of life, serious adverse events, and symptom severity. Secondary outcomes were suicide or suicide-attempts, self-harm, and level of functioning. We included 19 trials randomising 3,447 participants. All trials were at high risk of bias. Three single trials met the required information size needed to confirm or reject realistic intervention effects. One single trial showed no evidence of a difference between 6 versus 12 months dialectical behavioral therapy for borderline personality when assessing quality of life, symptom severity, and level of functioning. One single trial showed evidence of a beneficial effect of adding booster sessions to 8 and 12 weeks of internet-based cognitive behavioral therapy for depression and anxiety when assessing symptom severity and level of functioning. One single trial showed no evidence of a difference between 20 weeks versus 3 years of psychodynamic psychotherapy for mood- or anxiety disorders when assessing symptom severity and level of functioning. It was only possible to conduct two pre-planned meta-analyses. Meta-analysis showed no evidence of a difference between shorter- and longer-term cognitive behavioural therapy for anxiety disorders on anxiety symptoms at end of treatment (SMD: 0.08; 95% CI: -0.47 to 0.63; p = 0.77; I2 = 73%; four trials; very low certainty). Meta-analysis showed no evidence of a difference between shorter and longer-term psychodynamic psychotherapy for mood- and anxiety disorders on level of functioning (SMD 0.16; 95% CI -0.08 to 0.40; p = 0.20; I2 = 21%; two trials; very low certainty). The evidence for shorter versus longer-term psychotherapy for adult mental health disorders is currently unclear. We only identified 19 randomised clinical trials. More trials at low risk of bias and at low risk of random errors assessing participants at different levels of psychopathological severity are urgently needed. PROSPERO CRD42019128535.


A study of the in vitro interaction between ethanol, and triazolam and its two metabolites using human liver microsomes.
Triazolam is widely used as an ultrashort-acting anxiolytic drug and hypnosedatives and its effect appears at very low doses. Ethanol is used as a social drug worldwide. Sometimes, toxic interactions occur following combined administration of these two drugs. In this study, we have investigated the interaction between alcohol and triazolam in vitro. The interaction effects between alcohol and triazolam were examined by a mixed-function oxidation reaction using a human liver microsomal preparation. Triazolam and its two metabolites (alpha-hydroxytriazolam: alpha-OH triazolam, 4-hydroxytriazolam: 4-OH triazolam) were measured by HPLC/UV. The production of alpha-OH triazolam and 4-OH triazolam was shown to be weakly inhibited by 13-29% (p < 0.05) and 8-14%,respectively, by ethanol (20-80 mM). These results using a human liver microsomal preparation show that the formation of both metabolites of triazolam is weakly inhibited by ethanol. Toxic levels may be reached by simultaneous administration of ethanol and triazolam.


A Study on the Time-Effect and Dose-Effect Relationships of Polysaccharide from Opuntia dillenii against Cadmium-Induced Liver Injury in Mice.
The purpose of this study was to evaluate the protective effect of Opuntia dillenii (Ker-Gaw) Haw. polysaccharide (ODP) against cadmium-induced liver injury. Cadmium chloride (CdCl2) was used to construct a mice evaluation model, and the indicators chosen included general signs, liver index, biochemical indicators, blood indicators, and pathological changes. A dose of 200 mg/kg ODP was applied to the mice exposed to cadmium for different lengths of time (7, 14, 21, 28, and 35 days). The results showed that CdCl2 intervention led to slow weight growth (reduced by 13−20%); liver enlargement; significantly increased aspartate aminotransferase (AST, 45.6−52.0%), alanine aminotransferase (ALT, 26.6−31.3%), and alkaline phosphatase (ALP, 38.2−43.1%) levels; and significantly decreased hemoglobin (HGB, 13.1−15.2%), mean corpuscular hemoglobin (MCH, 16.5−19.3%), and mean corpuscular hemoglobin concentrations (MCHC, 8.0−12.7%) (p < 0.01). In addition, it led to pathological features such as liver cell swelling, nuclear exposure, central venous congestion, apoptosis, and inflammatory cell infiltration. The onset of ODP anti-cadmium-induced liver injury occurred within 7 days after administration, and the efficacy reached the highest level after continuous administration for 14 days, a trend that could continue until 35 days. Different doses (50, 100, 200, 400, and 600 mg/kg) of ODP have a certain degree of protective effect on cadmium-induced liver injury, showing a good dose−effect relationship. After 28 days of administration of a 200 mg/kg dose, all pathological indicators were close to normal values. These findings indicated that ODP had positive activity against cadmium-induced liver injury and excellent potential for use as a health food or therapeutic drug.


Hypoxia induces proliferation via NOX4-Mediated oxidative stress and TGF-β3 signaling in uterine leiomyoma cells.
Uterine leiomyomas, the most common tumors of the female reproductive system, are known to have a hypoxic microenvironment. However, the role of such environment in leiomyoma pathobiology remains unknown. The objective was to determine the effects of hypoxia on leiomyoma cells, and the mechanisms. We found that hypoxia induces proliferation and inhibits apoptosis in human leiomyoma cells. This pro-proliferative effect was accompanied by an increase in reactive oxygen species (ROS) generation and the expression of NADPH oxidase 4 (NOX4). The specific NOX4 inhibitor GLX351322 abrogated this hypoxia-induced ROS generation, cellular proliferation, and apoptosis inhibition. To further investigate the mechanism of NOX4-mediated proliferation, we treated leiomyoma cells grown in normoxia with media from leiomyoma cells cultured under hypoxia. This resulted in increased ROS generation and NOX4 expression, suggesting the hypoxia-induced effects are mediated by an autocrine mechanism. We worked to identify the nature of this autocrine factor. We found that the expression of TGF-β3 and its downstream signaling target pSmad3, are increased in hypoxic leiomyoma cells. To examine the hypothesis that TGF-β3 is, at least, a part of this autocrine mechanism, we treated hypoxic leiomyoma cells with the HIF-1α inhibitor KC7F2 which we discovered to ameliorate the hypoxia-induced TGF-β3 expression. Furthermore, pharmacologic inhibition with the TGF-β/Smad inhibitor SB431542 reduced hypoxia-induced NOX4 expression and ROS generation and attenuated cell proliferation. Thus, we have identified a novel mechanism by which hypoxia induces proliferation in leiomyoma cells. This finding adds to our understanding of leiomyoma pathobiology and can help in identifying new therapeutic targets.


Stener-like lesions due to radial collateral ligament rupture in the metacarpophalangeal joints of two adjacent fingers: A case report and review of literature.
Rupture of the collateral ligaments in the metacarpophalangeal (MCP) joint of a finger is less common than in the thumb. Literature about these lesions is sparse but the number of chronic injuries reported underlies the number of cases overlooked by physicians at the first visit. A Stener-like lesion is characterized by interposition of the extensor hood or the sagittal band between the torn collateral ligament of the MCP joint of a finger and its insertion. It was originally described as interposition of the adductor aponeurosis of the thumb. We present the first case of a Stener-like lesion in ruptured radial collateral ligaments of the MCP joint of two adjacent fingers.


[Benign salivary gland-type tumors of the bronchus: expression of high molecular weight cytokeratins].
Primary lung tumors showing features of salivary gland-type neoplasms are extremely rare, and their immunohistochemical profile has been seldom studied. We report two cases of bronchial pleomorphic and mucous gland adenomas and study the expression of markers such as TTF-1 and high molecular weight keratins in these tumors. Both tumors were endobronchial. The pleomorphic adenoma also had a well-circumscribed parenchymal component, with a biphasic morphology composed of epithelial and myoepithelial cells in a background of myxoid and hyaline stroma. The mucous gland adenoma displayed papillary and dilated glandular structures. In both cases, epithelial cells showed strong and diffuse cytoplasmic staining with high molecular weight cytokeratins (cytokeratin 5/6 and keratin 903), and lacked TTF-1 expression. This immunoprofile provides useful clues for the histogenesis of pulmonary benign salivary gland-type adenomas and helps in distinguishing them from primary adenocarcinomas in small biopsy specimens.


Exploring emergency department visits: factors influencing individuals' decisions, knowledge of triage systems and waiting times, and experiences during visits to a tertiary hospital in Saudi Arabia.
In recent years, there has been an increased utilization of emergency departments (EDs) in many countries. Additionally, it is reported that there are major delays in delivering care to ED patients. Longer waiting times are associated with poor patient satisfaction, whereas an understanding of the triage process increases satisfaction. This study aimed to assess ED visitor's awareness of the triage procedure and their preferences regarding delayed communication. Cross-sectional study of King Abdulaziz Medical City - Emergency Department visitors using a previously validated questionnaire (Seibert 2014) which was translated to Arabic, piloted, and then used for this study. A total of 334 questionnaires were returned. The mean age of respondents was 33 years. Regarding primary care physicians, only 16% of respondents said that they have one. About 21% of those tried to communicate with them before coming to the ED. Even though only 11% of respondents knew exactly what triage is, 51% were able to correctly explain why some patients are seen before others. Statistical analysis did not show any factors that are associated with increased knowledge of triage. Most respondents (75%) want to hear updates regarding delays with 69% of them preferring to be updated every 30 min. This study showed that the majority of patients do not know what triage means and that most of them want to know how the ED works. Moreover, a lot of respondents said that they do not have a primary care physician. These results support increasing patient awareness by education and involving them if any delay happens.


Self-reported "communication technology" usage in patients attending a cardiology outpatient clinic in a remote regional hospital.
This study assessed the perceived usage of, and attitudes toward, communication technologies (mobile phone and texting, e-mail, and the World Wide Web) in patients attending a cardiology clinic with a view to guiding future health service redesign. This was performed in a remote regional hospital serving both urban and rural populations. A self-completion questionnaire was completed by a convenience sample of 221 patients attending a general cardiology clinic. The questions asked about patients' access to and use of technology at home. Data collected also included age, gender, travel time to the clinic, mode of travel, and whether the respondent was accompanied to the clinic. Appropriate statistical tests were used with significance taken at the 0.05 level. Age was the strongest predictor of use of communication technologies, with younger patients more likely to use e-mail, Web, mobile phone, and texting. However, frequency of use of e-mail was not related to age. It is encouraging that over 99% of patients used at least one communication technology. This study has highlighted that there may be several potential barriers to the widespread implementation of communication technologies in general cardiology patients. Cognizance should be taken of these findings when attempting service redesign.


The surface display of haemolysin from Vibrio harveyi on yeast cells and their potential applications as live vaccine in marine fish.
HL1 gene encoding haemolysin from Vibrio harveyi SF-1 was expressed in yeast cells and the expressed haemolysin was displayed on the cell surface. After induction for 36h in galactose-containing medium, one-third of the cells contained the displayed protein and the displayed cells had haemolytic activity on erythrocytes from flounder. The double diffusion agar analysis showed that the sera from the flounder immunized with the displayed yeast cells having the haemolytic activity could form precipitate with the purified haemolysin. ELISA analysis indicated that immunization times had great influence on increased production of the specific antibody against haemolysin in turbot immunized with the displayed yeast cells having the haemolytic activity. After the challenge with V. harveyi SF-1, it was found that earlier protection in flounder and significant protection in turbot, both of which were immunized with the displayed yeast cells having the haemolytic activity, were achieved. These results suggested that the displayed yeast cells with the haemolytic activity could be used as potential live vaccine in marine fish.


Over-the-scope clip closure of gastric endoscopic submucosal dissection-induced ulcer in a patient with bleeding tendency.
A man in his 70s, with a history of dementia and aplastic anemia, was diagnosed with a gastric tumor. Thrombocytopenia due to aplastic anemia may cause bleeding after endoscopic submucosal dissection. Then, ulcer closure using the over-the-scope clip system was performed for prevention of post-operative bleeding.


A population-based evaluation of the thrombolysis in myocardial infarction risk score for unstable angina and non-ST elevation myocardial infarction.
The Thrombolysis in Myocardial Infarction risk score (TIMI-RS) for unstable angina/non-ST elevation myocardial infarction (MI) was developed in patients presenting with unstable angina accompanied by high-risk features or non-ST elevation MI to determine early risk stratification. The validity in patients presenting for emergency care with symptoms suggestive of acute coronary syndrome (ACS) has not been well established, and the present study sought to do so by evaluating the TIMI-RS in a prospective fashion. A prospective TIMI-RS using seven variables was calculated in 245 patients admitted to the hospital with symptoms suggestive of ACS: (1) age > 65, (2) three or more cardiac risk factors, (3) ST deviation, (4) aspirin use within 7 days, (5) two or more anginal events over 24 h, (6) history of coronary stenosis, and (7) elevated troponin. Patients were contacted at 30 days and data were collected concerning major adverse cardiac events. In patients presenting with chest pain, a higher TIMI-RS was associated with an increase in major adverse cardiac events within 30 days. We found that the 30-day event rate was 0% for a score of 1, 20% for a score of 2, 24% for a score of 3, 42% for a score of 4, 52% for a score of 5, and 70% for a score of 6 or 7 (p < 0.0001). The TIMI-RS successfully differentiates early risk for major adverse cardiac events in a general population presenting with symptoms suggestive of acute coronary syndrome. A simple bedside calculation of the TIMI-RS provides rapid risk stratification, allowing facilitation of therapeutic decision making in patients with symptoms suggestive of ACS.


[generalized peritonitis in three cows following irrigation of the uterus in the puerperium].
Three cases of cows with a severe generalized peritonitis due to a perforated uterus following irrigation in puerperal disorder are described. Based on these events the legal aspects of the bovine uterus' irrigation during puerperium are discussed.


P-wave dispersion in children with acute rheumatic fever.
As a new and simple electrocardiographic marker, P-wave dispersion is reported to be associated with inhomogeneous and discontinuous propagation of sinus impulses. The current study aimed to investigate P-wave dispersion in children with acute rheumatic fever. The study population consisted of 47 children with acute rheumatic fever (29 patients with carditis and 18 patients without carditis) and 31 healthy control subjects. Maximum and minimum P-wave durations were measured from the 12-lead surface electrocardiogram. The P-wave dispersion was calculated as the difference between maximum and minimum P-wave durations. The maximum P-wave duration and the P-wave dispersion of the patients with and without carditis were significantly greater than those of the control subjects. The P-wave dispersion of the patients with carditis was significantly greater than that of the patients without carditis. In conclusion, the P-wave dispersion was higher in the children with acute rheumatic fever than in the healthy control subjects.


Anti-acne vulgaris effect including skin barrier improvement and 5α-reductase inhibition by tellimagrandin I from Carpinus tschonoskii.
Carpinus tschonoskii (CT) has been previously studied for various activities in the improvement of skin diseases. In the present study, we examined the in vitro anti-acne vulgaris (AV) effect of CT leaves (CTL) and tellimagrandin I (TI), one of the main ellagitannins from CT, including skin barrier improvement and 5α-reductase inhibitory activity. To test the anti-AV activities of CTL and TI, firstly, anti-oxidative and anti-inflammatory activities including DPPH radical scavenging activity, nitric oxide (NO) inhibitory activity, and cytokines [interleukin (IL)-6 and IL-8] were tested. Skin barrier improvement experiments were tested using developing cornified envelope (CE) formation, and filaggrin mRNA expression level was determined by RT-PCR. The 5α-reductase inhibitory activity was determined by measuring the testosterone levels in rat liver microsomes. CTL and TI showed potent anti-oxidative activity and anti-inflammatory activities. Especially, the cytokine production inhibitory activities of TI were found to be similar to the positive control, epigallocatechin gallate (EGCG). CTL and TI enhanced the CE formation and filaggrin mRNA expression levels and showed potent activities compared to that in the positive control, 1.5 mM Ca2+. In additionally, CTL and TI showed 5α-reductase inhibitory activities in a dose-dependent manner. The results showed that CTL and TI inhibit AV endogenous factors such as 5α-reductase and inflammatory cytokines and affect exogenous factors such as developing skin barrier function (CE and filaggrin levels). Therefore, CTL and TI may be plant-derived agent, promising in the treatment of acne vulgaris.


GABAergic pretectal terminals contact GABAergic interneurons in the cat dorsal lateral geniculate nucleus.
Anterograde tracing techniques combined with postembedding immunocytochemical staining were used to determine the gamma amino butyric acid (GABA) content of pretectogeniculate (PT-LGN) terminals and their postsynaptic targets. The results provide evidence that PT-LGN terminals are GABAergic and that they contact GABAergic interneurons. These results corroborate previous anatomical studies and support the idea that the PT-LGN projection functions to disinhibit thalamocortical cells in the dorsal lateral geniculate nucleus.


Distribution of antiretroviral therapy through private pharmacies and postal courier services during COVID-19 in Botswana: acceptability and reach of two out-of-facility individual differentiated service delivery models.
The advent of COVID-19 has put pressure on health systems as they implement measures to reduce the risk of transmission to people living with HIV (PLHIV) and healthcare workers. For two out-of-facility individual differentiated service delivery (DSD) models, we assessed acceptability of antiretroviral therapy (ART) distribution through private pharmacies and reach of home delivery of ART through courier services during the COVID-19 pandemic in Botswana. From 24 July to 24 August 2020, we conducted exit interviews with PLHIV receiving ART from 10 high-volume public facilities in Gaborone, and mapped and conducted an online survey with private pharmacies to assess willingness and capacity to dispense ART to PLHIV enrolled in the Botswana national ART program. We piloted ART home delivery from September 2020 to January 2021 in Gaborone and Kweneng East districts for PLHIV accessing ART at two Tebelopele Wellness Clinics. We used cascade analysis to measure the enrolment and eventual reach (percentage of those reached amongst those who are eligible) of ART home delivery. Sixty-one PLHIV and 42 private pharmacies participated. Of the PLHIV interviewed, 37 (61%) indicated willingness to access ART from private pharmacies and pay BWP50 (∼US$4) per refill for a maximum of two refills per year. All private pharmacies surveyed were willing to provide ART, and 26 (62%) would charge a dispensing fee (range = BWP50-100; ∼US$4-8) per refill. All pharmacies operated 12 h/day, 6 days/week and on public holidays. In the home delivery pilot, 650 PLHIV were due for refills, 69.5% (n = 452) of whom were eligible for home delivery. Of these, 361 were successfully offered home delivery and 303 enrolled (enrolment = 83.9%: female = 87.2%, male = 77.8%, p = 0.013). A total of 276 deliveries were made, a reach of 61%. Providing ART through private pharmacies and home delivery was acceptable in Botswana during COVID-19. Surveyed pharmacies were willing and able to dispense ART to PLHIV attending public sector facilities for free or for a nominal fee. Additionally, using courier services for ART home delivery is a novel and viable model in countries with a reliable courier service like Botswana and should be scaled up, particularly in urban areas.


Production of tremorgenic toxins by Penicillium janthinellum Biourge: a possible aetiological factor in ryegrass staggers.
Topsoil, herbage and faeces collected during an outbreak of ryegrass staggers in sheep were examined for tremorgenic penicillia. No such fungi were recovered from the plant material, but they were found among the predominant fungi in the soil and faecal samples. The commonest species of Penicillium, and almost the only tremorgenic species encountered, was Penicillium janthinellum Biourge. When fed to sheep, the mycelium of this fungus evoked a number of the clinical signs seen in field cases of ryegrass staggers. Two tremorgenic toxins were isolated from the mycelial felts and available evidence indicates that they are verruculogen and fumitremorgin A. P. janthinellum also produced these tremorgens when cultured in moist, autoclaved soil, but not in unheated soil. The results obtained from this study are in accord with the hypothesis that ryegrass staggers is caused by tremorgenic mycotoxins.


Prevalence of type 2 diabetes mellitus (T2DM) in India: A systematic review (1994-2018).
To conduct a systematic and critical review of published studies on prevalence of Type 2 diabetes mellitus (T2DM) in urban and rural areas of India. We conducted a literature search in PubMed, EMBASE and Web of Science using the terms 'prevalence', 'Type 2 diabetes, 'India', 'urban' and 'rural' for English language articles published during January 1994-December 2018. We selected articles that reported the results of original studies that randomly sampled adults aged 15-80 years, and which reported T2DM prevalence based on the actual examination of blood samples. Of 1751 articles screened by titles and abstracts, 37 fulfilled our inclusion criteria. Majority (28 of 37; 76%) of studies were from South India, especially from the states of Tamil Nadu, Andhra Pradesh, Kerala and Karnataka. The prevalence of T2DM showed a wide range from 1.9% to 25.2%. Only 11 studies covering 24 regions separately reported the data by urban or rural location. Albeit inconsistent, 17 studies reported prevalence of T2DM by age group. In this systematic review, we show that there remains an ambiguity about the actual prevalence of T2DM from India due to several factors. The findings underscore a strong need for having periodic regional surveillance involving appropriate epidemiological methods.


Guanine content and Dermatophagoides pteronyssinus allergens in house dust samples.
The study of the relationship between the guanine content and Dermatophagoides pteronyssinus (Dp) allergens in house dust samples is reported. Mattress and carpet dust of bedrooms from 22 different homes constituted the house dust samples. The guanine content was determined by quantitative measurements and the mite allergenicity by two immunochemical assays with a partially purified extract of Dp as internal reference: RAST inhibition and crossed and rocket line immunoelectrophoresis. A large scale range of guanine content was obtained among the 22 house dust samples studied (0.01 to 1.78 mg/0.1 gm of dust). Data of RAST inhibition, analyzed according to parallel line bioassay, demonstrated no significant difference between the slopes of the reference and the house dust sample lines, but a 100-fold variation in the relative Dp potencies was observed. By crossed and rocket line immunoelectrophoresis technique, the presence and the amounts of major Dp allergens (Der p I and Dp 4) were established in most house dust extracts. A significant correlation was found between the guanine content of the house dust samples and their relative Dp potencies (r = 0.86) on the one hand, and with their relative content of Der p I and Dp 4, two major Dp allergens (r = 0.75 and r = 0.74, respectively) on the other hand; in each case, a quantitative relationship was established. These results suggest that the guanine determination could assess mite allergens in house dust and may be a useful tool in large-scale investigations of house dust.


Interferon and antibody titrations using haemagglutinating Togaviridae and trypsinized human erythrocytes.
Several Togaviridae of the alphavirus and flavivirus genera agglutinate trypsinized human group O erythrocytes (THOE) (Shortridge and Hu, 1976). Haemagglutinin titers of Semliki Forest virus (SFV) and Japanese encephalitis virus (JEV) measured with THOE were equivalent to, if not higher than, those obtained with Embden gander erythrocytes, even with unextracted haemagglutinin. Results obtained with THOE in JEV haemagglutination-inhibition tests on sera taken from a previously infected individual over a 20-yr period were similar to those measured during the initial JEV infection. The inhibition of SFV haemagglutinin production as measured with THOE was a very sensitive bioassay for chicken interferon: interferon titers were 6- to 10-fold higher than those obtained with the vesicular stomatitis virus plaque-reduction method. The generally greater availability of human erythrocytes (including those stabilized with glutaraldehyde), the simplicity of the trypsin treatment, and the possibility of using unextracted haemagglutinin recommend this technique for use with haemagglutinating Togaviridae.


The unfulfilled potential of mucosal immunization.
Recent events involving the global coronavirus pandemic have focused attention on vaccination strategies. Although tremendous advances have been made in subcutaneous and intramuscular vaccines during this time, one area that has lagged in implementation is mucosal immunization. Mucosal immunization provides several potential advantages over subcutaneous and intramuscular routes, including protection from localized infection at the site of entry, clearance of organisms on mucosal surfaces, induction of long-term immunity through establishment of central and tissue-resident memory cells, and the ability to shape regulatory responses. Despite these advantages, significant barriers remain to achieving effective mucosal immunization. The epithelium itself provides many obstacles to immunization, and the activation of immune recognition and effector pathways that leads to mucosal immunity has been difficult to achieve. This review will highlight the potential advantages of mucosal immunity, define the barriers to mucosal immunization, examine the immune mechanisms that need to be activated on mucosal surfaces, and finally address recent developments in methods for mucosal vaccination that have shown promise in generating immunity on mucosal surfaces in human trials.


Assessment of antibacterial activity of EndoREZ.
The aim of this in vitro study was to evaluate antibacterial activity of a new resin based sealer, EndoREZ in comparison with 5 other sealers: AH 26, Diaket, Sultan, Apexit, and RoekoSeal. The effect of 6 different sealers on the growth of 3 bacteria (Enterococcus faecalis, Staphylococcus aureus, and Pseudomonas aeruginosa) was measured using the agar diffusion test (ADT) and direct contact test (DCT). For ADT, 200 microL bacterial suspensions were spread on agar plates and freshly mixed sealers were applied to uniform wells punched in the agar. The zones of inhibition of bacterial growth were measured at 24 hours, 48 hours, 7 days, and 10 days. For DCT, 2 sets of sealers were prepared: fresh and 24-hour samples. Fresh samples were used within 20 minutes of mixing time while 24-hour samples were allowed to set in a humid atmosphere at 37 degrees C for 24 hours before testing. Sealers were mixed and placed on the walls of microtiter plate wells and 10-microL bacterial suspensions were allowed to directly contact the sealers for 1 hour. Fresh media were added and 15 microL were transferred from this plate to another plate containing fresh medium (215 microL). Bacterial growth of this last plate was then measured using spectrophotometer every hour over 16 hours. ADT results indicated that EndoREZ, Apexit, and RoekoSeal did not show any antibacterial activity. In DCT results, AH 26 and Sultan were potent bacterial growth inhibitors. EndoREZ is not as potent a bacterial growth inhibitor as Sultan and AH 26.


[Social cognition in autism. A survey of functional imaging studies].
Autism spectrum disorders (autism, Asperger's syndrome, high-functioning autism) are characterized by a common pattern of marked impairments in social interactions. Deficits have been described in face processing, facial emotion recognition, and social attribution ("theory of mind") or generally speaking in social cognition. Some studies have shown that these impairments are already detectable in early childhood, leading to the assumption that the underlying cause is an early disruption of neuronal development. Accordingly, neuroimaging data have revealed alterations of structure and function in the brains of autistic children, adolescents, and adults. The present review gives a systematic overview of the existing literature on functional imaging studies using experimental paradigms of social cognition, i.e. face discrimination, facial emotion recognition, and theory of mind in autistic disorders.


A study of lower urinary tract symptoms for the Korean women aged 30 and over.
The purposes of this study were (1) to identify the prevalence of urinary incontinence (UI) and lower urinary tract symptoms (LUTS) for Korean women, (2) to evaluate the LUTS scores of the subjects in relation with each UI patterns and general characteristics, and (3) to identify affecting factors developing LUTS by using self-administered questionnaire. Community-based cross-sectional study was conducted for 3,371 women aged 30 to 89 years old who were allocated at six provinces in South Korea. UI and LUTS were assessed by validated symptom scales including the International Prostate Symptom Score. Of all the respondents, 63.4% had experienced UI more than once a month during the prior 12 months. Among the respondents, 36.6% had no UI, 47.5% had stress UI, 0.4% had urge UI, and 15.5% had mixed UI. The mean LUTS score of the total respondents was 7.8 +/- 4.1. The LUTS was significantly predicted by age (p < .0001) and mixed UI (p < .0001), and 79.4% of variance in LUTS was explained. The highest LUTS scores were shown in the subjects with mixed UI, and we found that LUTS scores increased with age.


Homomultimeric protease in the hyperthermophilic bacterium Thermotoga maritima has structural and amino acid sequence homology to bacteriocins in mesophilic bacteria.
A novel homomultimeric protease (> 669 kDa), based on 31 kDa subunits, was purified from cell extracts of the hyperthermophilic bacterium Thermotoga maritima. This protease exhibits activity toward chymotrypsin and trypsin substrates, optimally at 90 degrees C and pH 7.1, and has a half-life of 36 min at 95 degrees C. Transmission electron microscopy established that the protease consists of a large globular assembly which appears circular from the front view. The function of this protease in T. maritima remains unclear, although putative homologs include a 29 kDa antigen from Mycobacterium tuberculosis and a 31 kDa monomer of a high molecular weight bacteriocin produced by Brevibacterium linens [Valdes-Stauber, N. and Scherer, S. (1996) Appl. Environ. Microbiol. 62, 1283-1286]. The relationship of these mesophilic proteins to the T. maritima protease suggests that their antibacterial activity may involve elements of proteolysis, and raises the prospect for antimicrobial ecological strategies in hyperthermophilic niches.


The exploded hand syndrome: logical evaluation and comprehensive treatment of the severely crushed hand.
Severe compressive trauma to the hand presents with multiple soft-tissue and osseous manifestations that often appear unrelated, leading to underrecognition and potential undertreatment of the complex injuries. Approaching the crushed hand with a logical and systematic diagnostic plan allows surgeons to recognize the location and severity of the injury portfolio and direct comprehensive treatment. Both for emphasis and for the purpose of describing the hydraulic mechanism of tissue failure, the term exploded hand syndrome is proposed. The exploded hand connotes the compendium of clinical findings that include skin failure at the webspaces or glabrous border, atypical (usually longitudinal) fracture patterns of the tubular bones, and axial carpal dissociations. These are accompanied by extensive compromise of the interosseous musculature that is extruded or may exhibit evolving compartment syndrome. Understanding the trauma mechanism and patterns of injury in the exploded hand will maximize awareness and guide surgical reconstruction and rehabilitation.


Evaluation of completeness, consistency and non-duplication of leprosy notification data on the Notifiable Health Conditions Information System, João Pessoa, Paraíba, Brazil: a descriptive study, 2001-2019.
to analyze the completeness, consistency and non-duplication of leprosy notification data in João Pessoa, Paraíba, Brazil, 2001-2019. this was a descriptive study, conducted with data from the Notifiable Health Conditions Information System, which checked for "duplication" (acceptable: < 5%), "completeness" (excellent = incompleteness ≤ 5%) and "consistency" (excellent: ≥ 90.0%), based on the proportion of complete and consistent fields. the sample consisted of 2,410 notifications. Duplication was acceptable (0.3%). The completeness of the "bacilloscopy", "affected nerves", "examined contacts" and "reactive episode" fields was very poor (more than 50% incomplete). Consistency between the "operational classification" and "initial treatment regimen" fields was excellent (99.6%), while consistency between "operational classification" and "clinical form" was low (50.7%). although duplication was acceptable, poor completeness of diagnosis and follow-up fields hinders epidemiological analysis, recognition of the status of the disease and adoption of measures to control it.


Ultrafast strain engineering in complex oxide heterostructures.
We report on ultrafast optical experiments in which femtosecond midinfrared radiation is used to excite the lattice of complex oxide heterostructures. By tuning the excitation energy to a vibrational mode of the substrate, a long-lived five-order-of-magnitude increase of the electrical conductivity of NdNiO(3) epitaxial thin films is observed as a structural distortion propagates across the interface. Vibrational excitation, extended here to a wide class of heterostructures and interfaces, may be conducive to new strategies for electronic phase control at THz repetition rates.


Extracellular matrix (ECM) modulates the EGF-induced migration of liver epithelial cells in serum-free, hormone-supplemented medium.
The influence of the extracellular matrix (ECM) glycoproteins collagen IV, laminin (LN), and fibronectin (FN) on the in vitro migration of epithelial cells was studied using the ECM migration track method (4) with preparations immunostained for LN and FN. The locomotion of rat liver epithelial cells stimulated to migrate in serum-free medium by epidermal growth factor (EGF) in the presence of insulin is inhibited by substratum-bound FN. The inhibition is concentration-dependent up to 0.7 microgram of the protein per cm2. Neither LN nor collagen IV decreased the number of migrating cells, indicating that the inhibition is a specific effect of fibronectin. The data also indicate that the FN-mediated inhibition of migration is an additional and not alternative mechanism to the well-established contact inhibition of locomotion (1) which also occurs in liver epithelial cell cultures. The system is being used for a further analysis of the factors that influence migration of normal and neoplastic epithelial cells and the biochemical mechanisms underlying the migration reaction.


Biosynthetic studies on saframycin A, a quinone antitumor antibiotic produced by Streptomyces lavendulae.
The biosynthesis of saframycin A, a heterocyclic quinone antitumor antibiotic isolated from Streptomyces lavendulae 314, was studied by feeding experiments with 14C and 13C precursors. Highly increased production of saframycin A and prolongation of the maximum production period of saframycin A were attained by constant pH control of the culture and by addition of chloramphenicol to the culture. The biosynthetic origin of the quinone skeleton common to the saframycin group was confirmed to be two tyrosine molecules which condense to generate the basic ring system of saframycin A. Feeding experiments with [1-13C]tyrosine showed specific labeling of C-11 and C-21 carbons of saframycin A, and the enrichment of the carbons was 40-fold over natural abundance. Two O- and two C-methyl and one N-methyl carbons arose directly from methionine, and alanine and glycine were the precursors for the pyruvoyl amide side chain of saframycin A.


Effects of vibration training on quality of life in older adults: a preliminary systematic review and meta-analysis.
Older adults experience reduced quality of life (QOL). Vibration training has been applied in older adults. However, it remains inconclusive whether vibration training improves QOL in this population. This review summarized the effects of vibration training in changing eight domains of the Short Form-36 (SF-36) among older adults. Five randomized controlled trials enrolling 212 participants were included. The mean difference (MD) was calculated as the effect size measurement. Meta-analyses were completed for each of the eight SF-36 domains. Relative to control groups, vibration training is more effective in improving five QOL domains: physical function (MD = 15.61, p < 0.001), physical role limitations (MD = 12.71, p = 0.001), general health (MD = 10.59, p < 0.001), social function (MD = 11.60, p < 0.001), and vitality (MD = 6.86, p = 0.002). Vibration training may not lead to greater improvements for the other three domains (MD = 0.13-3.25, p values = 0.21-0.96) than the control groups. Vibration training showed a low attrition rate of 7.1%. Vibration training programs may significantly improve five of eight SF-36 QOL domains. While three domains did not demonstrate significant improvements, results were slightly in favor of vibration training compared to the control groups. More rigorous studies are necessary to further confirm the effectiveness of vibration training on QOL in older adults.


Anti-AnWj causing acute hemolytic transfusion reactions in a patient with aplastic anemia.
AnWj is a high-prevalence red blood cell (RBC) antigen in the ISBT 901 series. Only nine reports of anti-AnWj have been published since it was first documented in 1972; two of these cases involved transfusion reactions. We present a case of a patient with aplastic anemia who developed anti-AnWj with clinically significant hemolysis after transfusion of AnWj-positive RBCs. A 56-year-old woman with aplastic anemia developed a pan-reactive antibody with clinically significant hemolysis after transfusion of RBCs. Investigations included antibody identification by serologic methods at the national immunohematology reference laboratory and the in vitro monocyte-monolayer assay (MMA) to predict clinical significance. The antibody was identified as having specificity for the AnWj antigen. The posttransfusion MMA indicated that the antibody had complement-fixing capability highly likely to cause clinically significant acute hemolytic transfusion reactions. The patient required long-term transfusion support with AnWj-negative RBCs and Lu(a-b-) RBCs of the In(Lu) type which have reduced AnWj expression. Cross-Canada and international collaboration was required to obtain rare units for transfusion. A case of acute hemolytic transfusion reaction caused by anti-AnWj is reported in a patient with aplastic anemia requiring allogeneic stem cell transplantation. This is the second documented case of anti-AnWj to cause a hemolytic transfusion reaction. The case demonstrates the complexity of managing patients with rare antibodies and the importance of international collaboration in the management of these difficult cases.


Pathological immuno-reactions of glial cells in Alzheimer's disease and possible sites of interference.
A significant role of a pathological glial cell activation in the pathogenesis of Alzheimer's disease is supported by the growing evidence that inflammatory proteins, which are produced by reactive astrocytes, promote the transformation of diffuse beta-amyloid deposits into the filamentous, neurotoxic form. A number of vicious circles, driven by the release of TNF-a and free oxygen radicals from microglial cells, may cause an upregulated microglial activation and their production of interleukin-1 which triggers, secondarily, the crucial activation of astrocytes. Reactive functional changes of glial cells seem to be controlled by an altered balance of the second messengers Ca2+ and cAMP and can be counterregulated by the endogenous cell modulator adenosine which strengthens the cAMP-dependent signalling chain. A further reinforcement of the homeostatic adenosine effects on glial cells by pharmaca, such as propentofylline, may add to neuroprotection in Alzheimer's disease.


Atypical aspects of hypertensive encephalopathy in childhood.
Four patients with hypertensive encephalopathy and misleading focal symptomatology are reported in order to point out the problems of differential diagnosis. The first patient, together with a classical syndrome of hypertensive encephalopathy, had peculiar EEG features consistent with a possible diagnosis of herpes simplex encephalitis. Case 2 presented with a complex clinical syndrome associating bizarre spells suggestive of a psychiatric condition with ocular symptoms pointing to an upper brain stem involvement. The third child was remarkable because of the presence of neuroradiological signs compatible with a space-occupying lesion of the posterior fossa not eventually found after a surgical exploration performed as an emergency procedure. The last patient had central nervous system signs in the context of a Guillain-Barré syndrome: in this case the central symptomatology would not fit the already described pattern of encephalomyelo-radiculo-neuropathy but had to be entirely ascribed to the ill controlled arterial hypertension.


Detection of favorable alleles for plant height and crown rust tolerance in three connected populations of perennial ryegrass (Lolium perenne L.).
Plant height, which is an estimator of vegetative yield, and crown rust tolerance are major criteria for perennial ryegrass breeding. Genetic improvement has been achieved through phenotypic selection but it should be speeded up using marker-assisted selection, especially in this heterozygous species suffering from inbreeding depression. Using connected multiparental populations should increase the diversity studied and could substantially increase the power of quantitative trait loci (QTL) detection. The objective of this study was to detect the best alleles for plant height and rust tolerance among three connected populations derived from elite material by comparing an analysis per parent and a multipopulation connected analysis. For the studied traits, 17 QTL were detected with the analysis per parent while the additive and dominance models of the multipopulation connected analysis made it possible to detect 33 and 21 QTL, respectively. Favorable alleles have been detected in all parents. Only a few dominance effects were detected and they generally had lower values than the additive effects. The additive model of the multipopulation connected analysis was the most powerful as it made it possible to detect most of the QTL identified in the other analyses and 11 additional QTL. Using this model, plant growth QTL and rust tolerance QTL explained up to 19 and 38.6% of phenotypic variance, respectively. This example involving three connected populations is promising for an application on polycross progenies, traditionally used in breeding programs. Indeed, polycross progenies actually are a set of several connected populations.


Immunological evaluation of a novel multi-antigenic DNA vaccine encoding SAG1, SAG3, MIC4, GRA5, GRA7, AMA1and BAG1 against Toxoplasma gondii in BALB/c mice.
Many recent studies have been conducted to find new DNA vaccines based on Toxoplasma gondii antigens. DNA vaccines encoding complex of different antigens showed better immune responses compared to single antigen vaccine. In this study, we constructed a DNA vaccine encoding SAG1, SAG3, MIC4, GRA5, GRA7, AMA1 and BAG1 against T. gondii, and evaluated the immune response it induced in BALB/c mice. For this purposes, thirty BALB/c mice were randomly divided into three groups containing tenmice each. There were two negative control groups (PBSand pVAX1 vector) and one vaccination group (pVAX1-MAF, Multantigenic Fragment). On days 0, 14 and 28, the mice were immunized intramuscularly, and 5 weeks later they were challenged with T. gondii RH strain. The immune responses were evaluated using lymphocyte proliferation assay, T-cell subsets detection, and measurement of antibody and cytokine levels. The results showed that mice immunized with pVAX1-MAF developed high levels of IL-2, IL-12, IgG and IFN- γ as well as CD3+CD4+ T cells. In addition, the survival time of mice immunized by pVAX1-MAF was longer than that control mice. In conclusion, our results show that the multiple DNA vaccine encodingSAG1, SAG3, mic4, GRA5, GRA7, AMA and BAG1effectively enhanced humoral and cellular immune responses, and prolonged the survival time. Together this would suggest that further investigation may result in a promising candidate vaccine to treat toxoplasmosis.


Biodegradation mechanism of chlorpyrifos by halophilic bacterium Hortaea sp. B15.
For decades, most of the developing nations have relied on chlorpyrifos for insecticidal activity in the agriculture sector. It is a common chlorinated organophosphorus pesticide that has been widely used to control insects to protect plants. This study aimed to investigate the effects of environmental characteristics such as salinity, pH, temperature, and surfactant on Hortaea sp. B15 mediated degradation of chlorpyrifos as well as enzyme activity and metabolic pathway. The highest bacterial growth (4.6 × 1016 CFU/mL) was achieved after 20 h of incubation in a 100 mg/L chlorpyrifos amended culture. The fit model and feasible way to express the chlorpyrifos biodegradation kinetics in normal condition and optimized was a first-order rate equation, with an R2 value of 0.95-0.98. The optimum pH for chlorpyrifos biodegradation was pH 9, which resulted in a high removal rate (91.1%) and a maximum total count of 3.8 × 1016 CFU/mL. Increasing the temperature over 40 °C may inhibit microbial development and biodegradation. There was no significant effect of culture salinity on degradation and bacterial growth. In the presence of non-ionic surfactant Tween 80, the maximum chlorpyrifos degradation (89.5%) and bacterial growth (3.8 × 1016 CFU/mL) was achieved. Metabolites such as 3,5,6-trichloropyridin-2-ol and 2-pyridinol were identified in the Hortaea sp. B15 mediated degradation of chlorpyrifos. According to the findings, Hortaea sp. B15 should be recommended for use in the investigation of in situ biodegradation of pesticides.


Application of diffusion tensor-based tractography in treatment of brain arteriovenous malformations: a systematic review.
There is no systematic review investigating the utility of Diffusion tensor-based tractography findings for treating brain arteriovenous malformations (bAVMs). This systematic review aims to investigate the outcomes following bAVM treatment when tractography data is incorporated into treatment planning. PubMed/MEDLINE, Scopus, and Cochrane Library, were searched for published studies. Prospective or retrospective studies involving at least one patient with confirmed bAVM and available data on tractography and clinical outcomes were included. A total of 16 studies were eligible for this review, consisting of 298 patients. 48.2% of patients were female. The mean age of the patients was 27.5 years (range: 5-77). Stereotactic radiosurgery (SRS) and microsurgical resection each were the treatment of choice in eight studies, respectively. Two-hundred forty-eight patients underwent SRS as the primary treatment, while microsurgery was used to resect the bAVMs in 50 patients. The corticospinal tract, optic pathway, and arcuate fasciculus were the most widely investigated white matter tracts. Tractography disruption and failure frequencies were 19.1% and 1.8%, respectively. The pooled proportions (95% CI) of obliteration rates were 88.78% (73.51-95.76) for microsurgery and 51.45% (13-17-88.10) following SRS. Treatment-related non-hemorrhagic complications rates occurred in 24.2% and 9.9% of patients who underwent microsurgical resection and SRS, respectively. Tractography findings can contribute to providing a more accurate dosimetry analysis of functional white matter tracts at risk prior to SRS and minimizing the surgical morbidity following microsurgical resection.


Inhibitory and stimulatory effects of phorbol ester on vasopressin-induced cellular responses in cultured rat aortic smooth muscle cells.
In rat aortic smooth muscle cells, vasopressin (AVP) induces prostacyclin (PGI2) production, probably as the consequence of phospholipase C activation. Our study analyzes the effects of phorbol 12-myristate 13-acetate (PMA)-induced protein kinase C (PKC) activation on AVP-induced inositol 1,4,5-trisphosphate formation, cytosolic free Ca2+ concentration [( Ca2+]c), and PGI2 production. PMA rapidly decreased PKC activity in the cytosol of smooth muscle cells, while increasing it transiently in the membranes with a maximum around 20 min. Prior exposure of the cells to PMA resulted in a transient inhibition of both AVP-induced inositol 1,4,5-trisphosphate formation and [Ca2+]c rise. This was inversely correlated with membraneous PKC activity and partially reversed by the PKC inhibitor staurosporine. In contrast, pretreating the cells with PMA markedly potentiated A23187 or AVP-induced PGI2 production. Under those conditions, AVP-induced PGI2 production did not correlate either with PMA-induced membranous PKC activity or with AVP-induced PLC activation. However, this potentiating effect of PMA was reversed by staurosporine and was not mimicked by the 4 alpha-phorbol, an inactive analogue of PMA. Thus, the possibility is raised that, while inhibiting AVP-induced PLC activation, PMA-induced PKC activation increases the Ca2+ sensitivity of the cellular signaling system leading to PGI2 production.


What does climbing mean exactly? Assessing spatiotemporal gait characteristics of inclined locomotion in parrots.
At what inclination does climbing begin? In this paper, we investigate the transition from walking to climbing in two species of parrot (Agapornis roseicollis and Nymphicus hollandicus) that are known to incorporate both their tail and their craniocervical system into the gait cycle during vertical climbing. Locomotor behaviors ranging in inclination were observed at angles between 0° and 90° for A. roseicollis, and 45°-85° degrees for N. hollandicus. Use of the tail in both species was observed at 45° inclination, and was joined at higher inclinations (> 65°) by use of the craniocervical system. Additionally, as inclination approached (but remained below) 90°, locomotor speeds were reduced while gaits were characterized by higher duty factors and lower stride frequency. These gait changes are consistent with those thought to increase stability. At 90°, A. roseicollis significantly increased its stride length, resulting in higher overall locomotor speed. Collectively these data demonstrate that the transition between horizontal walking and vertical climbing is gradual, incrementally altering several components of gait as inclinations increase. Such data underscore the need for further investigation into how exactly "climbing" is defined and the specific locomotor characteristics that differentiate this behavior from level walking.


Can Alberta's primary care networks provide any lessons for Medicare Locals?
Australia's Medicare Locals are in a formative period, and any comparison so far has focused on the United Kingdom.


Cognitive impairment and psychiatric symptoms in 133 patients with diseases associated with cerebellar degeneration.
The authors performed a chart review to determine the frequency with which neurologists detect cognitive and psychiatric symptoms in patients with cerebellar degeneration. Psychopathology, including depression, personality change, cognitive impairment, anxiety, and psychosis was noted in 51% of 133 patients.


Bypassing the central bottleneck after single-task practice in the psychological refractory period paradigm: evidence for task automatization and greedy resource recruitment.
In this research, the controversial issue of whether the central bottleneck can be bypassed through task automatization was investigated. To examine this issue, participants received six single-task practice sessions with an auditory-vocal task (low vs. high pitch). We then assessed dual-task performance using the analytically tractable psychological refractory period (PRP) paradigm, in which the highly practiced auditory-vocal task was presented as Task 2, along with an unpracticed visual-manual Task 1. The results provide evidence of bottleneck bypass for virtually all the participants (17 out of 20). Several converging tests suggest that the bottleneck reemerged, however, in a follow-up experiment with tasks presented in the opposite order (auditory-vocal Task 1 and visual-manual Task 2). One possible explanation is that tasks greedily recruit central resources when available, even though they can operate without central resources when unavailable.


Transcriptional activation of gene expression by pluronic block copolymers in stably and transiently transfected cells.
Amphiphilic block copolymers of poly(ethylene oxide) and poly(propylene oxide) (Pluronics) enhance gene expression, but the mechanism remains unclear. We examined the effects of Pluronics on gene expression in murine cell models (NIH3T3 fibroblasts, C2C12 myoblasts, and Cl66 mammary adenocarcinoma cells) transfected with luciferase and green fluorescent protein. Addition of Pluronics to stably or transiently transfected cells enhanced transcription of the reporter genes. mRNA levels of the heat-shock protein hsp68 were also increased, whereas a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase, was unaffected. Fibroblast and myoblast cells transfected with PathDetect cis-Reporting System constructs were used to examine the involvement of the nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1) in Pluronics enhancement. Pluronics enhanced reporter gene expression controlled by NF-kappaB in both cell models. They also increased expression of a gene under AP-1 in a fibroblast cell line, but not in a myoblast cell line. Activation of the inflammation signaling pathway in myoblast cells by Pluronics was shown by increased IkappaB phosphorylation. No cytotoxicity was observed at doses of Pluronics at which gene expression was increased. Overall, these results indicate that Pluronics can increase the transcription of genes, in part, through the activation of selected stress signaling pathways.


[Primary lymphosarcoma of the lung (author's transl)].
The histological, histochemical and cytological changes were reported in 6 patients with primary lymphosarcoma of the lung. All cases are diffuse lymphocytic lymphosarcomas, histochemically with a similar enzymatic behaviour. Cytologically, small lymphocytes with different degrees of anaplasia were observed.


Molecular-genetic effects of cadmium chloride.
We studied the effect of cadmium chloride on: (1) the DNA of human cells; (2) the mutagenic effect of reproducing Kilham virus; (3) the synthesis of virus-induced interferon, and (4) the reproduction of oncogenic (mammalian leucosis) virus. Cadmium chloride caused degradation of DNA in human- and rat-embryo cells. Culture infected by the virus in the presence of cadmium sulphate had the highest yield of cells with chromosomal aberrations. Cadmium chloride caused marked inhibition of the virus-induced synthesis of interferon. The introduction of cadmium chloride into diploid cells infected by the leucosis virus caused a 3-4 fold increase in the yield of virus-induced transformation foci.


Developmental potential of selectively enucleated immature mouse oocytes upon nuclear transfer.
Selective enucleation (SE) was applied to germinal vesicle (GV) oocytes by removing the chromatin attached to nuclear envelope, and leaving the liquid contents of GV in the cytoplast. However, after reconstruction with 1/8 blastomeres or fetal fibroblasts (FFs) neither the maturation efficiency nor the frequency of normal (asymmetric) division was improved as compared with completely enucleated (CE) oocytes. Chromosomal aberrations introduced with somatic nuclei were not rescued in SE oocytes either. On the other hand, timing of maturation division in SE GV oocytes, but not in CE GV oocytes, reconstructed with GV-karyoplasts was like in the control. After maturation and fertilization in vitro, SE oocytes reconstructed with 1/8 blastomeres developed nucleolated donor pronuclei, contrary to CE oocytes. The latter could be rescued with nucleoli-containing nucleus, but not anucleolate nucleus, from a 1/2 blastomere. SE oocytes reconstructed with FFs contained nucleolated pronuclei upon activation, unlike CE GV oocytes. These experiments show that the ooplast nucleolar material and/or embryonic nucleolus are indispensable for pronuclei formation. SE oocytes reconstructed with 1/8 blastomeres or FFs failed to cleave after activation or in vitro fertilization. Control GV oocytes enucleolated before fertilization seized cleavage at the 6-cell stage, as oppose to intact GV oocytes, which in 50.9% yielded morulae/blastocysts. These results suggest that ooplast nucleolar material is essential for the cleavage divisions. Activation of cumulus-enclosed SE GV oocytes matured in hormone-supplemented medium and fused to 1/2 blastomere-karyoplasts, yielded morulae, and blastocysts in 45.5% and 23.4% of reconstructed oocytes, respectively.


The unique profile of cord blood natural killer cells balances incomplete maturation and effective killing function upon activation.
Cord blood (CB) is increasingly used as a source of stem cells for hematopoietic stem cell transplantation, and natural killer (NK) cells may be the effectors of the antileukemic response observed after CB transplantation. Here, we analyzed the phenotype and functions of CB NK cell subsets. We determined that the percentage of NK cells was higher in CB compared with peripheral blood (PB). Furthermore, there was a higher percentage of the CD56(bright) subset in CB. CB NK cells reached a late stage of differentiation, but exhibited higher expression of NKG2A and expressed fewer killer-cell immunoglobulin-like receptors, suggesting an incomplete maturation. CB NK cells highly expressed CXCR4, but did not express L-selectin, highlighting unique homing properties of CB NK cells. CB NK cells proliferated in response to interleukin-2 and degranulated in response to stimulation with tumor cells, but failed to lyse K562 cells in (51)Cr-release assay. CB NK cells exhibited a lower interferon-γ production in comparison with PB NK cells. Culture with IL-2 increased CB NK cell functions. Our study sheds light on CB NK cell properties and highlights the potential of CB as a source of NK cells for immunotherapy.


Platelet polyphosphate induces fibroblast chemotaxis and myofibroblast differentiation.
Platelets secrete many pro-wound healing molecules such as growth factors and cytokines. We found that releasates from activated human platelets induced the differentiation of cultured murine and human fibroblasts into a myofibroblast phenotype. Surprisingly, most of this differentiation-inducing activity was heat-stable, suggesting it was not due to the protein component of the releasates. Inorganic polyphosphate is a major constituent of platelet-dense granules and promotes blood coagulation and inflammation. We aim to investigate the contribution of polyphosphate on myofibroblast differentiating activity of platelet releasates. Using NIH-3T3 cells and primary human fibroblasts, we examined the effect of human platelet releasates and chemically synthesized polyphosphate on fibroblast differentiation and migration. We found that the myofibroblast-inducing activity of platelet releasates was severely attenuated after incubation with a polyphosphate-degrading enzyme, and that fibroblasts responded to platelet-sized polyphosphate by increased levels of α-smooth muscle actin, stress fibers, and collagen. Furthermore, fibroblasts were chemotactic toward polyphosphate. These findings indicate that platelet-derived polyphosphate acts as a cell signaling molecule by inducing murine and human fibroblasts to differentiate into myofibroblasts, a cell type known to drive both wound healing and fibrosing diseases. Polyphosphate therefore not only promotes early wound responses through enhancing fibrin clot formation, but also may play roles in the later stages of wound healing, and, potentially, progression of fibrotic diseases, by recruiting fibroblasts and inducing their differentiation into myofibroblasts.


Metagenomics uncovers a new group of low GC and ultra-small marine Actinobacteria.
We describe a deep-branching lineage of marine Actinobacteria with very low GC content (33%) and the smallest free living cells described yet (cell volume ca. 0.013 μm(3)), even smaller than the cosmopolitan marine photoheterotroph, 'Candidatus Pelagibacter ubique'. These microbes are highly related to 16S rRNA sequences retrieved by PCR from the Pacific and Atlantic oceans 20 years ago. Metagenomic fosmids allowed a virtual genome reconstruction that also indicated very small genomes below 1 Mb. A new kind of rhodopsin was detected indicating a photoheterotrophic lifestyle. They are estimated to be ~4% of the total numbers of cells found at the site studied (the Mediterranean deep chlorophyll maximum) and similar numbers were estimated in all tropical and temperate photic zone metagenomes available. Their geographic distribution mirrors that of picocyanobacteria and there appears to be an association between these microbial groups. A new sub-class, 'Candidatus Actinomarinidae' is proposed to designate these microbes.


Formulation Development and Evaluation of Novel Vesicular Carrier for Enhancement of Bioavailability of Poorly Soluble Drug.
Niosomes are a vesicular carrier system comprised of a Nonionic surfactant bilayer surrounding an aqueous compartment. Niosomes are presumed to raise the intake of the poorly water-soluble drugs by M cells of Peyer's patches present in the intestine's lymphatic tissues, thereby avoiding the first-pass metabolism and increasing its oral bioavailability. Biodegradability, nonimmunogenic nature, minimal side effects, low cost, good stability, and flexibility to incorporate hydrophilic and lipophilic drugs are other advantages of niosomes. To formulate and evaluate a novel vesicular carrier system of a poorly soluble drug Lurasidone hydrochloride for the enhancement of its solubility and bioavailability. The thin-film hydration technique used to prepare Lurasidone hydrochloride loaded niosomes using different grades of nonionic surfactants like Brij, Span, and Tween. They evaluated for particle size, zeta potential, percent entrapment efficiency, in-vitro drug release, and in-vivo study. Niosomes comprised of Brij S-100 in drug: cholesterol: surfactant (1:1:1) showed particle size (1.15 ± 0.21 μm) and percent entrapment efficiency (97.02 ± 0.21%) and was selected for further studies. Various pharmacokinetic parameters like Cmax (281.27ng/ml), Tmax (5 h), and AUC (2640.197) were found to be significantly improved compared to plain drug solution. The Niosomal formulation could be the promising drug delivery system for the controlled and sustained release of Lurasidone.


Effect of intra-operative autonomic nerve stimulation on pelvic nerve preservation during radical laparoscopic proctectomy.
This study assessed the effect of intra-operative electrical nerve stimulation (INS) on pelvic autonomic nerve preservation (PANP) during laparoscopic resection for rectal cancer. A total of 189 consecutive cases of radical laparoscopic proctectomy were included. PANP was assessed visually or with INS. Urinary function was evaluated by residual urine volume (RUV), International Prostatic Symptom Score (IPSS) and recatheterization rate. Erectile function was evaluated using the International Index of Erectile Function (IIEF-5) scale. INS successfully confirmed PANP in 65 (91.5%) patients, while direct vision confirmed PANP in only 72 (61.0%) patients. Compared with the successfully confirmed patients, failed patients in the INS group exhibited higher postoperative RUV (100.0 ± 34.6 vs 25.2 ± 13.6 ml, P = 0.003), higher IPSS (7 days, 20.0 ± 8.6 vs 6.5 ± 2.4, P = 0.012; 1 month, 13.5 ± 6.0 vs 5.3 ± 1.9, P = 0.020; 6 months, 11.7 ± 5.1 vs 4.5 ± 1.7, P = 0.018), a greater number of incidences of a micturition disorder (66.7% vs 1.5%, P = 0.000), higher recatheterization rates (33.3% vs 1.5%, P = 0.017) and a lower IIEF score at 3 months (8.25 ± 0.96 vs 10.93 ± 1.99, P = 0.012) and 6 months (12.50 ± 1.29 vs 15.63 ± 1.65, P = 0.001) postoperatively. Compared with the vision group, the INS group had less deterioration in postoperative RUV (31.5 ± 26.4 vs 54.0 ± 46.7 ml, P = 0.000), lower IPSS (7 days, 7.7 ± 5.0 vs 11.0 ± 6.6, P = 0.000; 1 month, 6.0 ± 3.3 vs 7.6 ± 5.4, P = 0.012) and higher IIEF score (3 months, 10.69 ± 2.07 vs 9.42 ± 2.05, P = 0.001; 6 months, 15.36 ± 1.85 vs 13.64 ± 2.00, P = 0.000) as well as a lower incidence of urination disorders (7.0% vs 17.8%, P = 0.038). INS is effective for the accurate evaluation of PANP during radical laparoscopic proctectomy. Combined with INS, laparoscopic proctectomy is more effective in urogenital function protection.


Correction: A microRNA-4516 inhibitor sensitizes chemo-resistant gastric cancer cells to chemotherapy by upregulating ING4.
[This corrects the article DOI: 10.1039/C8RA06419A.].


Retinoic acid enhances killing of neuroblastoma cells by Newcastle disease virus.
Newcastle disease virus (NDV), an avian pathogen, selectively replicates in and kills neuroblastoma (NB) cells, but not normal fibroblasts in vitro and in vivo in nude mice. NDV cytotoxicity towards NB cells is enhanced by N-myc oncogene amplification. To further define the antineoplastic effects of NDV, we examined NDV's interaction with NB cells following short-term exposure to the differentiating agent, all-trans retinoic acid (RA), and to neuraminidase. The human NB cell line IMR-32, after treatment with 50 mumol/L RA, became eight times more sensitive to NDV in a cytotoxicity assay. A time course study to determine the optimal incubation period of IMR-32 cells with RA indicated that a fourfold increase in sensitivity towards NDV killing occurred after only 8 hours of RA incubation prior to addition of virus. Maximal sensitivity was achieved at 24 hours of RA incubation and remained constant for longer incubation periods (up to 72 hours). The sensitization of IMR-32 NB cells to NDV was constant for RA doses between 3 mumol/L and 50 mumol/L. Plaque formation, which indicates replication, virus spread and cytotoxicity by a single infectious virus particle, was also enhanced by RA. This effect does not appear to require N-myc amplification in the target NB cells since RA had similar effects upon the high N-myc (IMR-32) and the low N-myc expressing cells (SK-N-SH). Enhanced sialylation has been shown by others to mediate the growth inhibitory effects of RA on a variety of tumor lines. Removal of sialic acid from the IMR-32 NB cell surface using Clostridium neuraminidase (2.7 mg/mL) inhibited 75% of NDV plaque formation. These results demonstrate that NDV killing of two NB cell lines is enhanced using clinically achievable levels of RA and that sialylation of the NB cell surface is important for virus binding and cytotoxicity.


Chorionic thickness and PlGF concentrations as early predictors of small-for-gestational age birth weight in a low risk population.
SGA is associated with higher incidence of postnatal complications, including suboptimal neurodevelopment and increased cardiovascular risk. Screening for SGA, carried out at 11-13 (+ 6d) gestational weeks enables to reduce or completely eliminate the above mentioned complications. The aim of this study was to assess the correlation between chorionic thickness, concentration of PIGF protein and foetal birth weight in a single low-risk pregnancy. The study included 76 patients at 11-13 (+ 6d) gestational weeks, monitored throughout preg-nancy. Ultrasound examinations identified the location and thickness of the chorion by measuring it in its central part at its widest point in a sagittal section. Additionally, at each visit venous blood was collected to determine the level of PlGF, PAPP-A, and BhCG. A significant positive correlation (r = 0.37) was found between the foetal weight and chorionic thickness. This correlation was affected by the location of the chorion and a significant negative correlation was observed between the level of PLGF, FHR, weight and length of the newborn. Maternal early-pregnancy BMI did not affect neonatal weight and body length, FHR, chorionic thickness, and the levels of PlGF, PAPP-A, and BhCG. The preliminary analysis indicates an association between chorionic thickness assessed during ultrasound at 11-13 (+ 6d) gestational weeks, PIGF levels assayed at the same time and birth weight. Increasing chorion thickness was accompanied by increasing foetal birth weight. PlGF level showed an inversely proportional effect on the foetal weight. This correlation was significant for the posterior location of the chorion.


The role of Bcl-2 family members in tumorigenesis.
The Bcl-2 family consists of about 20 homologues of important pro- and anti-apoptotic regulators of programmed cell death. The established mode of function of the individual members is to either preserve or disturb mitochondrial integrity, thereby inducing or preventing release of apoptogenic factors like Cytochrome c (Cyt c) from mitochondria. Recent findings also indicate further Bcl-2-controlled mitochondria-independent apoptosis pathways. Bcl-2 represents the founding member of the new and growing class of cell death inhibiting oncoproteins. In this review, we try to briefly summarize current models of Bcl-2 family function and to outline the work demonstrating the influence of deregulated Bcl-2 family member expression on tumorigenesis and cancer therapy. Since several Bcl-2 homologues, in addition to influencing apoptotic behaviour, also impinge on cell cycle progression, we discuss possible implications of this additional role for the expression of Bcl-2 family members in tumor cells.


Synthetic long non-coding RNAs [SINEUPs] rescue defective gene expression in vivo.
Non-coding RNAs provide additional regulatory layers to gene expression as well as the potential to being exploited as therapeutic tools. Non-coding RNA-based therapeutic approaches have been attempted in dominant diseases, however their use for treatment of genetic diseases caused by insufficient gene dosage is currently more challenging. SINEUPs are long antisense non-coding RNAs that up-regulate translation in mammalian cells in a gene-specific manner, although, so far evidence of SINEUP efficacy has only been demonstrated in in vitro systems. We now show that synthetic SINEUPs effectively and specifically increase protein levels of a gene of interest in vivo. We demonstrated that SINEUPs rescue haploinsufficient gene dosage in a medakafish model of a human disorder leading to amelioration of the disease phenotype. Our results demonstrate that SINEUPs act through mechanisms conserved among vertebrates and that SINEUP technology can be successfully applied in vivo as a new research and therapeutic tool for gene-specific up-regulation of endogenous functional proteins.


Rare malignant adnexal tumour of the skin involving distal phalanx of right thumb with co-existing primary lung cancer in a 72-year-old patient: A case report.
Malignant adnexal tumours of the skin are a group of rare malignancies. These tumours can further differentiate into eccrine, apocrine, sebaceous, sweat duct, or ceruminous glands within the skin or follicular cells. Sebaceous carcinoma, a malignant adnexal tumour of the skin, is a rare and malignant tumour of the sebaceous glands. They can occur anywhere in the body where sebaceous glands are present, the most common being the head and neck region. Here we report a case of a 72-year-old man who presented with a bleeding ulcer on the distal right thumb, which was progressively increasing in size. Biopsy and histology confirmed the diagnosis of MATS with sebaceous differentiation. He had been diagnosed with metastatic non-small cell lung carcinoma six months back. SC is a rare and unusual tumour amounting to less than 1% of all cutaneous malignancies. Phalanges are an infrequent extra-ocular site of involvement, and initial presentation can be mistaken for a benign occurrence. Any patient presenting with extra-ocular SC is advised to undergo genetic and immunohistochemistry testing to rule out complex genetic syndromes like Muir Torre syndrome and Cowden syndrome.


Effects of common carotid artery damage on anti-platelet-aggregability and PGI2 production in rats.
The effects of vascular damage on platelet function were investigated in rats. Common carotid artery specimens 4 mm in length were dissected from male Wistar rats and exposed to ultrasonic treatment or rubbing of the intimal surface. In some cases, carotis was dissected after ligation for 4 hr. The specimens were fixed on a stirring bar and agitated in platelet-rich plasma added with ADP. After determining platelet aggregability, the plasma was subjected to radioimmunoassay for 6-keto-prostaglandin F1 alpha (6-K-PGF1 alpha). Anti-platelet-aggregability in the arterial specimens was significantly greater in the sonicated, rubbed or ligated specimens than in the intact group, probably due to the effect of prostacyclin (PGI2). The measurement of 6-K-PGF1 alpha levels yielded similar results. Endogenous arachidonic acid in the vessel wall seems to be utilized in the production of PGI2, which probably acts only on local platelets. The findings indicate the presence of a mechanism that inhibits the formation of platelet thrombi by the accelerated production of PGI2 under conditions favorable for the generation of thrombosis.


Applying adult emergence as an endpoint in a post-exposure laboratory test using two midge species (Diptera: Chironomidae).
Several approaches have been used to evaluate biological impairment in aquatic ecosystems which can be categorized as either laboratory or field. In the recent years, the laboratory toxicity test approach has been extended to field exposures where ambient factors are allowed to influence the test response. Field exposures of laboratory test organisms require method modifications. In this paper, a novel in situ method is described which measures growth, survival and emergence of sediment inhabiting insects (Diptera: Chironomidae) that are used in standardized laboratory toxicity testing. Two standard chironomid species (Chironomus riparius and Chironomus tentans) were used to test the suitability of the approach and to compare the performance of the species. The larvae were transferred to the laboratory for emergence after 7 days in situ exposure which was compared to laboratory responses. Growth, survival and emergence were significantly lower in the in situ pre-exposure than in the laboratory. Also, emergence success was significantly lower in one reference sediment (LMR) than in the other test sediments in both in situ and the laboratory treatment. These lower response levels likely resulted from sediment characteristics and artifacts related to the exposure in the in situ chamber. Feeding and water quality within the exposure chamber appear to be factors that may differ markedly from the laboratory exposure and may affect organism responses. C. riparius developed (growth, emergence time) faster than C. tentans in all treatments, otherwise the species responded similarly. C. riparius may be a better alternative for the chronic in situ exposures because of shorter exposure times and reduced feeding requirements.


Progesterone and the immunology of pregnancy.
The foetal-placental unit is a semi-allograft and the immunological recognition of pregnancy, together with the subsequent response of the maternal immune system, is necessary for a successful pregnancy. This recognition of pregnancy results in an upregulation of progesterone receptors on activated lymphocytes amongst placental cells and decidual CD56+ cells. In the presence of sufficient progesterone, these cells synthesise progesterone induced blocking factor (PIBF), a mediator that exerts substantial anti-abortive activities. PIBF affects B cells and induces an increased production of asymmetric, non-cytotoxic antibodies. It also alters the profile of cytokine secretion by activated lymphocytes resulting in an increase in the production of non-inflammatory, non-cytotoxic interleukins (IL) (e.g. IL-3, IL-4 and IL-10) and a reduction in the production of inflammatory, cytotoxic cytokines (e.g. interferon (IFN)-delta, tumour necrosis factor (TNF)-alpha and IL-2). PIBF also inhibits the cytotoxicity of natural killer (NK) cells by blocking their degranulation and perforin release, as well as inhibiting IFN-delta, TNF-alpha and IL-2-mediated transformation of NK cells into detrimental lymphokine activated killer (LAK) cells.


A new type of congenital dysfibrinogen, fibrinogen Bremen, with an A alpha Gly-17 to Val substitution associated with hemorrhagic diathesis and delayed wound healing.
We have identified a new type of A alpha Gly-17 to Val substitution in a congenital dysfibrinogen, fibrinogen Bremen, derived from a 15-year-old boy having manifested easy bruising and delayed wound healing. The functional abnormality was characterized by altered fibrin monomer polymerization, which became evident by increasing the salt concentration and pH. A synthetic tetrapeptide with a sequence of the amino-terminal segment of normal fibrin alpha-chain, Gly-Pro-Arg-Val, substantially inhibited polymerization of both normal and the patient-derived fibrin monomers. A synthetic tetrapeptide with the Bremen type sequence of Val-Pro-Arg-Val inhibited polymerization of the patient's fibrin monomers partially at a peptide: fibrin monomer molar ratio of 4,000:1, and that of normal one at a much higher ratio of 10,000:1. Likewise, a synthetic peptide Ala-Pro-Arg-Val with a replacement of the Gly residue by another aliphatic amino acid Ala inhibited similarly the patient's fibrin monomer polymerization. Thus, the hypothetical two-pronged socket-like structure consisting of the alpha-amino group of the amino-terminal Gly and the guanidino group of an Arg at position 3 of the normal fibrin alpha-chain seems to be restored considerably in the mutant fibrin alpha-chain at low ionic strengths and pH's, despite the replacement of the amino-terminal Gly by another aliphatic amino acid Val.


Generation and characterization of cardiomyocytes under serum-free conditions.
In vitro culturing of mammalian cells provides an elegant platform to study cell signaling, interactions, and metabolism as well as proliferation and differentiation processes. Often, these cells are cultured and maintained in sera obtained from animals such as horses, cows, and rabbits. The sera used for this purpose fluctuates in composition from individual animals and, hence, influences the cellular growth and differentiation at different magnitudes. This poses a need to use a substitute for sera in cell culture systems to overcome the observed variations. Here, we present and compare protocols for culturing of embryonic stem (ES) cells in serum-free conditions, derivation of germ layers, and cardiac differentiation of ES cells in both serum-free and serum-containing culture conditions. Differentiated embryoid bodies by serum-free protocols produce significantly increased frequencies of clusters of cardiac cells beating stronger than found in serum-containing media. Therefore, we conclude that the use of serum replacement media (SRM) in our experiments led to more specific differentiation but reduced proliferation because these SRMs contained reduced essential substances like growth factors and hormones. Unlike serum media, SRMs have a well-defined composition and are highly reproducible. Hence, SRM will be the ideal substitute for serum-containing media.


Positive platelet scintigram of a vertebral aneurysm presenting thromboembolic transient ischemic attacks.
We describe a patient with transient ischemic attacks secondary to a giant aneurysm who showed increased activity on platelet scintigrams at the origin of the left vertebral artery. This is assumed to be the first report of a presumed embolizing aneurysm with positive activity of labeled platelets. Platelet scintigraphy is useful for diagnosing transient ischemic attacks as being secondary to an aneurysm and was proved to provide direct evidence of a thromboembolic source in vivo.


Adaptive TS fuzzy MPC based on Particle Swarm Optimization-Cuckoo Search algorithm.
A novel technique to building an adaptable fuzzy model predictive control (AFMPC) is suggested in this study, based on the algorithm Particle Swarm Optimization-Cuckoo Search (PSOCS). This technique combines the particle swarm optimization (PSO) algorithm's iterative scheme with the Cuckoo Search (CS) algorithm's searching approach. To identify the system parameters at each time step, an on-line adaptive fuzzy identification is used. Based on a predictive technique, these factors are utilized to generate the goal function. The PSOCS method is then used to solve the optimization issue and select the best control signal. The suggested controller's utility is demonstrated using an experimental communicating three-tank system, in which the proposed approach-based PSOCS algorithm outperforms both the approach-based CS and the approach-based PSO algorithms.


Dopaminergic agents including 3-PPP and its enantiomers on medial septal self-stimulation.
The effects of several dopamine agonists were determined on medial septal self-stimulation in rats and compared with selected dopamine antagonists and with the psychostimulants, d-amphetamine and nomifensine. Apomorphine, 3-PPP, TL-99, N,N-dipropyl-5,6-ADTN and N,N-dipropyl-6,7-ADTN inhibited self-stimulation at dose ranges selective for the dopamine autoreceptor as indicated by biochemical studies. Haloperidol and molindone produced dose-related inhibition but sulpiride increased self-stimulation. D-amphetamine and nomifensine also increased responding. The agonist-induced inhibition differed from neuroleptic-induced inhibition of self-stimulation. Both (+) and (-) 3-PPP inhibited responding by a similar amount over the dose range 0.25-1.0 mg/kg. At higher doses, (-) 3-PPP further decreased responding whereas the effects of (+) 3-PPP plateaued at approximately 55% of controls. These studies show that dopamine agonists, like neuroleptics, inhibit medial septal self-stimulation. This effect appears to be mediated via autoreceptor activation. Differences between neuroleptic- and agonist-induced inhibition and the 3-PPP stereoisomer data accord with the hypothesis that behavioural inhibitory effects caused by autoreceptor activation are less severe than those caused by dopamine postsynaptic blockade.


Nexus between agro-ecological efficiency and carbon emission transfer: evidence from China.
The economy of China is growing rapidly. With this overwhelming growth, the country is experiencing a higher level of carbon emissions. Amid this backdrop, China is under immense pressure to reduce carbon emissions up to a sustainable level. This study adapted 31 provincial panel data from 2007 to 2017 using factor analysis system SBM-undesirable model to calculate the agro-ecological output of each province respectively and used a carbon transfer network impact analysis panel to calculate ecological performance impacts. Results show that (1) overall agro-ecological efficiency in China shows an upward trend but regional differences are evident. The efficiency in the eastern region is higher than that in the central and western regions but the extent of informatization in the central region is higher than that in the western region. (2) Informatization will significantly promote agro-ecological efficiency. (3) Changes in agricultural planting structure, agricultural value-added per capita, employment of human capital in the agricultural sector, and agricultural scale management are also important factors affecting agro-ecological growth. (4) China's amount of carbon transfer is growing year by year, and energy-intensive areas and heavy industry bases are undertaking carbon transfer from the eastern coastal regions; (5) Jiangsu, Henan, and Hebei (Hubei) have the highest centers between 2007 and 2012; (6) inter-provincial carbon transmission is concentrated mainly in the metal smelting and rolling processing industries as well as in the coal, heat, and supply industries.


Peer Education: Productive Engagement for Older African Americans in Recovery From Depression.
Older adults who have personal experience with the mental health service delivery system gain unique and potentially valuable insight from their treatment experiences. Research suggests that incorporating trained individuals in recovery from a mental illness (i.e., peer educators) into mental health service delivery roles results in substantial benefits for current mental health consumers, particularly for older adults and racial and ethnic minorities who may feel disenfranchised from the traditional mental health service delivery system. However, little research has examined the impact of participating in these activities on the peer educators themselves. This mixed methods study examines the experiences of 10 African American older adults in recovery from depression currently working as trained peer educators. Peer educators reported feeling more positive, feeling their lives had significantly improved, and feeling better in general due to their peer educator roles. This qualitative investigation highlights four unique themes that can explain the benefit of serving in this capacity (i.e., Community Engagement, Life Long Learning and Education, Mental Health Recovery and Productive Aging). This study suggests that serving has a peer educator has a number of beneficial outcomes for African American older adults in recovery from depression.