Farmers' willingness to pay for metal silo cereal storage technology in northeast Ethiopia.
In Ethiopia, cereal crops play a significant role in food security and income for most smallholder farmers. In the Gubalafto district, the environment is ideal for growing vital cereal crops such as sorghum, maize, and teff. However, various factors such as weevils, rodents, mold infestation, and lack of suitable storage materials were blamed for a post-harvest loss of cereal at the storage stage in the district. Hence, this research study was intended to identify factors affecting households' willingness to pay for metal silo cereal storage technology and the maximum willingness to pay for the technology. The study used both primary and secondary sources to gather the data. A total of 385 sample households were selected using a systematic random sampling technique. The semi-structural questionnaire was used to collect the primary data during a face-to-face interview, and double-bounded questions were also followed by open-ended questions. Combinations of data analysis methods such as descriptive, inferential statistics, and econometrics models were used. a binary probit regression model was used to identify factors that influenced farmers' willingness to pay for metal silo cereal storage technology. A bivariate probit regression model was also used to estimate the household's willingness to pay for metal silo cereal storage technology. The survey results showed that the majority (71.69%) of the sample households were willing to pay for metal silo cereal storage technology due to the severity of cereal post-harvest loss. Moreover, the binary probit model results revealed that household educational status, total household annual income, market accessibility, and extension service positively and significantly affected the household's willingness to pay decisions. The mean willingness to pay of households in open-ended and double-bounded methods was 4157 Ethiopian birr and 5147 Ethiopian Birr (ETB), respectively. In general, the result of the study revealed that farmers were more willing to adopt metal silo cereal storage technology due to its high-storage quality. Therefore, as a part of the recommendations, there should be great integration among farmers, metal manufacturing factories, local and regional governments to supply and offer metal silos technology for farmers at a reasonable price and time. Moreover, training should be arranged on how to use the metal silo technology to prevent post-harvesting loss during the storage time.


Magnetic field interactions of orthodontic wires during magnetic resonance imaging (MRI) at 1.5 Tesla.
Orthodontic appliances pose a potential risk during magnetic resonance imaging (MRI) due to forces on metallic objects within the static magnetic field of MRI systems. The aim of the present investigation was to measure forces on orthodontic wires caused by the static magnetic field of a 1.5-Tesla MRI system, and to assess the safety hazards associated with these forces. Thirty-two different orthodontic wires (21 arch wires, eight ligature wires and three retainer wires) were investigated in a 1.5-Tesla MRI system (Magnetom Symphony, Siemens Medical Solutions, Erlangen, Germany). The translational forces were measured using the deflection angle test (ASTM F2052-02); rotational forces were assessed on a 5-point qualitative scale. All retainer wires and the steel arch wires (the Noninium arch wire being the exception) were subjected to considerable rotational and translational forces within the MRI system's magnetic field. Translational forces were from 9.1- to 27.6-times as high as gravitational forces on these objects. Steel ligature wires and arch wires made of cobalt chromium, titanium molybdenum, nickel-titanium, and brass alloys showed no or negligible forces within the magnetic field. The translational and rotational forces within the MRI magnetic field should pose no risk to carefully-ligated arch wires. Steel retainer wire bonds should be checked to ensure secure attachment prior to an MRI investigation.


Lipoprotein apheresis in patients with peripheral artery disease and hyperlipoproteinemia(a).
Hyperlipoproteinemia(a) [Lp(a)-HLP] is a major risk factor for severe atherosclerosis. The present investigation sought to assess the effect of lipoprotein apheresis (LA) in patients with peripheral artery disease (PAD) and Lp(a)-HLP. In January 2013, we started a registry for Lp(a)-HLP patients who receive weekly LA in our center. So far, ten patients with severe PAD and isolated Lp(a)-HLP who recently underwent revascularization (index procedure) have been included. Pain level, ankle-brachial-index (ABI), transcutaneous oxygen pressure (tcpO2) and walking distance were determined before, as well as 1, 3, 6 and 12 months after initiation of LA. Furthermore, the mean time interval between revascularizations within the 12 months prior to the index procedure and up to 12 months after the index procedure was assessed. All analyzed parameters significantly improved under LA. When comparing the results before LA with the results after 12 months, the ankle-brachial-index increased from 0.5 ± 0.2 to 0.9 ± 0.1 (P < 0.001). The tcpO2 levels also increased from 42.9 ± 2.3 mmHg to 59.0 ± 8.9 mmHg (P < 0.001). The improved microcirculation was associated with a reduction of the mean pain level from 7.0 ± 1.5 to 2.0 ± 0.8 (P < 0.001) as determined using the visual analog scale. The walking distance increased from 87 ± 60 m to 313 ± 145 m (P < 0.001). Importantly, the frequency of revascularization procedures was strongly decreased under LA. All patients combined underwent 35 revascularizations within the 12 months prior to the index procedure (mean interval between two revascularizations: 104.3 days). Since the index procedure, only one revascularization was necessary within 79 patient-months under LA (mean interval: 2404.5 days, P < 0.001). LA improves circulation, oxygen supply, level of pain and walking distance in patients with severe PAD and Lp(a)-HLP. The frequency of revascularization procedures is strongly reduced under LA treatment.


Impact of mirabegron versus solifenacin on autonomic function and arterial stiffness in female overactive bladder syndrome: a randomized controlled trial.
The study aims to elucidate the impact of mirabegron versus solifenacin on autonomic function and peripheral arterial conditions in women with overactive bladder syndrome (OAB). All consecutive women with OAB were randomized to receive 12 weeks of mirabegron 25 mg or solifenacin 5 mg once per day. Heart rate variability, cardio-ankle vascular index, ankle-brachial pressure index, blood pressure, and heart rate were compared between the two groups. There were 87 women (mirabegron, n = 43; and solifenacin, n = 44) who completed 12-week treatment and underwent heart rate variability examination. Systolic blood pressure (median: - 4.5 to - 5.5 mmHg) and diastolic blood pressure (median: - 0.5 to - 3.5 mmHg) decreased after solifenacin treatment, and heart rate (median: + 2 bpm) increased after mirabegron treatment, despite of no between-group difference. In addition, posttreatment heart rate variability, cardio-ankle vascular index, and ankle-brachial pressure index did not differ compared with baseline; and there were no between-group differences. In conclusion, solifenacin might decrease blood pressure, and mirabegron might increase heart rate. Nonetheless, there were no significant impacts of 12-week mirabegron versus solifenacin treatment on autonomic function and arterial stiffness.


Laparoscopic treatment of primary ovarian pregnancy.
Ovarian pregnancy is an uncommon type of ectopic pregnancy. A 35-year-old, gravida 3, para 3 woman was admitted because of a vaginal bleeding of 17 days' duration after amenorrhea for 10 weeks. She had right lower quadrant pain. Serum beta-human chorionic gonadotropin concentration was 1530 mIU/ml. Transabdominal ultrasonography showed a normal-size uterus, empty uterine cavity, solid cystic mass 43 x 39 mm on the right adnexa, and no free fluid in the pouch of Douglas. Diagnostic operative laparoscopy under general anesthesia was performed for suspected ectopic pregnancy. Right oophorectomy was done because of minimal intact ovary tissue. It was later histopathologically confirmed as primary ovarian pregnancy. The woman experienced no postoperative complications.


Evidence of mechanical nonlinearity and frequency selective wave amplification in the cochlea.
A previously unsuspected mechanical response of the cochlear transduction mechanism has recently been discovered. It can be monitored outside the cochlear. Theorectical and experimental work leading to its discovery and identification are briefly reviewed. Its significance for models of the second filter and cochlear nonlinearity is discussed. An active wave amplification mechanism in the cochlea is proposed.


Effect of webinars in teaching-learning process in medical and allied health science students during COVID-19 pandemic: A cross-sectional study.
COVID-19 pandemic lockdown has brought all sectors to be dwindled with no exception of the academic system. Even professional courses like medical and allied health academic courses were also not spared. The academic requirements were not met as required to do so. Webinar has become a good source of virtual platform acting as a bridge for attaining the gaps in accomplishing the curriculum to the students during these curfew times. Our study aimed to know the value of webinars on teaching-learning processes among the medical and allied health science students in India. The study design is a cross-sectional study with 2084 students who attended at least one webinar. An online survey questionnaire was sent, and the data were collected on participant's perspective on the effectiveness of webinar, post webinar assessment by their satisfactory level of gain of information through webinars and their plan to apply in future. Participant's perspective on effectiveness of webinar showed 66.7% of agreement with the webinar use. In post webinar assessment, the use of webinar was in agreement with 69.9% of the participants. Furthermore, we observed a significant association with the gain of information in post webinar assessment (P < 0.05) and a significant association with their plan to apply in future (P < 0.05). Our results showed that the students were satisfied with the webinar teaching and acknowledged it to be an effective tool in the teaching-learning process to gain new knowledge and wish to attend webinars in future as a part of their curriculum. Thus, webinars have a constructive effect in the teaching and learning process in professional courses during pandemic lockdown.


Infundibular dilation: an anatomical variant or a pre-aneurysm? Advantages of assessment with three-dimensional rotational angiography.
Whether an infundibular dilation (ID) is an anatomical variant or a pre-aneurysm has not been clearly determined. The aim of the present study was to evaluate the anatomical change of IDs by use of three-dimensional rotational angiography (3DRA) with volume rendering (VR). One-hundred thirty-eight patients with known or suspected aneurysms, treated consecutively, underwent both two-dimensional digital subtraction angiography (2DDSA) and 3DRA with VR. Two readers evaluated the IDs or aneurysms blindly, using 2DDSA and 3DRA, according to the same diagnostic criteria. A 5-point scale of observer confidence was used to determine the presence of IDs or aneurysms. For 3DRA with VR, the relationship between IDs and aneurysms was classified as one of the three types: type I, protrusion or bulge from side wall of IDs; type II, aneurysms involving or enclosing IDs; or type III, aneurysms and IDs coexisting near each other but with some distance between them. The number of IDs found by 2DDSA and 3DRA with VR was 41 and 48, respectively. Five anterior choroidal arteries and two posterior communicating arteries IDs were missed by 2DDSA. According to 3DRA with VR, there were five IDs of type I, nine of type II, and 22 of type III. The 3DRA with VR appears superior to 2DRA for both diagnosing IDs and displaying the anatomical relationship between IDs and aneurysms. The findings also suggest that some IDs might progress to aneurysms or become a part of them, which should be carefully evaluated prior to operation.


Insight into lymphoid tissue morphogenesis.
Secondary lymphoid organs (SLO) are crucial structures for immune-surveillance and rapid immune responses allowing resident lymphocytes to encounter antigen-presenting cells that carry antigens from peripheral tissues. These structures develop during embryonic life through a tightly regulated process that involves interactions between haematopoietic and mesenchymal cells. Importantly, this morphogenesis potential is maintained throughout life since in chronic inflammatory conditions novel "tertiary lymphoid organs" can be generated by processes that are reminiscent of embryonic SLO development. In this review we will discuss early events in SLO morphogenesis, focusing on haematopoietic and mesenchymal cell subsets implicated on the development of lymphoid organs.


One-pot and one-step preparation of "living" cellulose nanofiber hydrogel with active double-bond via chemical vapor deposition.
Due to the existence of water, it is still a challenge to conduct chemical modification on cellulose nanofiber (CNF) hydrogels with active double bonds. A simple one-pot and one-step method for constructing "living" CNF hydrogel with double bond was created at room temperature. The chemical vapor deposition (CVD) of methacryloyl chloride (MACl) was used to introduce physical-trapped, chemical-anchored and functional double bonds into TEMPO-oxidized cellulose nanofiber (TOCN) hydrogels. TOCN hydrogel could be fabricated within just 0.5 h, the minimum dosage of MACl could be reduced to 3.22 mg/g (MACl/TOCN hydrogel). Furthermore, the CVD methods showed high efficiency for mass production and recyclability. Moreover, the chemical "living" reactivity of the introduced double bonds were verified by the freezing and UV crosslinking, radical polymerization and thiol-ene click reaction. Compared with pure TOCN hydrogel, the obtained functionalized TOCN hydrogel exhibited remarkable improvements in mechanical properties, with enhancements of 12.34 times and 2.04 times, as well as an increase in hydrophobicity by 2.14 times and a fluorescence performance improvement of 2.93 times.


[Effect of Landiolol for Atrial Fibrillation after Open Heart Surgery].
Postoperative atrial fibrillation (POAF) after open heart surgery is common complication. POAF is reported to prolong hospital stay and increase long-term mortality, therefore prevention of POAF is important. It is widely known that beta blocker decrease POAF, and we had used oral beta blocker after open heart surgery. We examined the effect of intraoperative and postoperative administration of intravenous beta blocker( landiolol) for POAF. We evaluated 291 consecutive patients who underwent open heart surgery from November 2016 to November 2018. Those who underwent open heart surgery after November 2017 were 145, and 100 of the patients( group A) had intraoperative and postoperative landiolol administration. Those who underwent open heart surgery before November 2017 were 146, and 100 of the patients (group B) did not have landiolol administration. The primary endpoint was incidence of POAF within 7 days after surgery. There was no significant difference in preoperative character between the groups, other than the ratio of males to females( group A:54 males, 46 females;group B:68 males, 32 females;p<0.05). The incidences of POAF were 20% and 36% in group A and group B, respectively( p<0.05). Intraoperative and postoperative administration of landiolol is effective for preventing POAF after open heart surgery.


Machine Learning for grouping nano-objects based on their morphological parameters obtained from SEM analysis.
Nanoparticles have unique properties that make them useful in a variety of applications, but their potential toxicity raises concerns about their safety. Accurate characterization of nanoparticles is essential for understanding their behavior and potential risks. In this study, we employed machine learning algorithms to automatically identify nanoparticles based on their morphological parameters, achieving high classification accuracy. Our results demonstrate the effectiveness of machine learning for nanoparticle identification and highlight the need for more precise characterization methods to ensure their safe use in various applications.


Biometry and visual function of a healthy cohort in Leipzig, Germany.
Cross-sectional survey of ocular biometry and visual function in healthy eyes across the life span of a German population aged 20 to 69 years (n = 218). Subject number in percent per age category reflected the percentage within the respective age band of the population of Leipzig, Germany. Measurements obtained: subjective and objective refraction, best-corrected visual acuity, accommodation, contrast sensitivity, topography and pachymetry with Scheimpflug camera, axial length with non-contact partial coherence interferometry, and spectral-domain optical coherence tomography of the retina. Pearson correlation coefficients with corresponding p-values were given to present interrelationships between stature, biometric and refractive parameters or their associations with age. Two-sample T-tests were used to calculate gender differences. The area under the logarithmic contrast sensitivity function (AULCSF) was calculated for the analysis of contrast sensitivity as a single figure across a range of spatial frequencies. The results of axial length (AL), anterior chamber depth (ACD) and anterior chamber volume (ACV) differed as a function of the age of the participants (rho (p value): AL -0.19 (0.006), ACD -0.56 (< 0.001), ACV-0.52 (< 0.001)). Longer eyes had deeper ACD (AL:ACD 0.62 (< 0.001), greater ACV (AL:ACV 0.65 (< 0.001) and steeper corneal radii (AL:R1ant; R2ant; R1post; R2post 0.40; 0.35; 0.36; 0.36 (all with (< 0.001)). Spherical equivalent was associated with age (towards hyperopia: 0.34 (< 0.001)), AL (-0.66 (< 0.001)), ACD (-0.52 (< 0.001)) and ACV (-0.46 (< 0.001)). Accommodation was found lower for older subjects (negative association with age, r = -0.82 (< 0.001)) and contrast sensitivity presented with smaller values for older ages (AULCSF -0.38, (< 0.001)), no change of retinal thickness with age. 58 % of the study cohort presented with a change of refractive correction above ±0.50 D in one or both eyes (64 % of these were habitual spectacle wearers), need for improvement was present in the young age-group and for older subjects with increasing age. Biometrical data of healthy German eyes, stratified by age, gender and refractive status, enabled cross-comparison of all parameters, providing an important reference database for future patient-based research and specific in-depth investigations of biometric data in epidemiological research. ClinicalTrials.gov # NCT01173614 July 28, 2010.


Exploring drivers' mental workload and visual demand while using an in-vehicle HMI for eco-safe driving.
Eco-safe driving is a promising approach to improve road safety while reducing transport emissions. The application of an eco-safe driving system is feasible with the support of vehicle-to-vehicle/infrastructure technologies. To guarantee system usability and safety appropriateness, a key precondition is to ensure that driver mental workload and visual demands required for using the system are reasonable. This study explored how drivers' mental workload and visual demands were affected when driving with an eco-safe driving HMI (human-machine-interface). Four in-vehicle eco-safe HMI information conditions were evaluated, including baseline, advice only, feedback only, and advice & feedback. Two traffic scenarios (stop-sign intersection with traffic vs. stop-sign intersection without traffic) were simulated using an advanced driving simulator. Behavioural variables (e.g. brake force, acceleration), visual variables (e.g. blink metrics, pupil size) and subjective workload scores were collected from 36 licensed Australian drivers. The experiment results showed that the HMI prompted drivers to apply a smooth and stable brake force when they approached the intersection and a smooth acceleration when they left the intersection. Drivers' mental workload indicated by visual measurements were consistent with their subjective reported workload levels. Drivers had a higher mental workload when they received and processed additional eco-safe information in the advice & feedback condition. An increase in mental workload induced by the in-vehicle cognitive task initiated more blink activities while the increase in visual demand caused by a complex road situation led to blink inhibition. The study shows the HMI could significantly promote eco-safe driving behaivours without causing excessive mental and visual workload of drivers.


Legumain Knockout Protects Against Aβ1-42-Induced AD-like Cognitive Deficits and Synaptic Plasticity Dysfunction Via Inhibiting Neuroinflammation Without Cleaving APP.
Neuroinflammation is the important pathological feature of Alzheimer's disease (AD). Legumain, a lysosomal cysteine protease, plays an important role in neuroinflammation during ischemic stroke and depressive disorder. Legumain is involved in AD process through cleaving APP; however, it is unclear if legumain can possibly modulate neuroinflammation without cleaving APP in AD. Thus, we established a mouse model of AD by single intracerebroventricular injections of Aβ1-42 in legumain knockout (KO) mice. The behavioral tests showed that legumain-KO effectively ameliorated cognitive impairment induced by Aβ1-42. Moreover, legumain deprivation significantly improves the synaptic plasticity damages in Aβ1-42-treated mice. Moreover, legumain-KO considerably inhibited the activation of microglia and reduced the expression of inflammatory cytokines in the hippocampus of Aβ1-42-treated mice. Interestingly, we found that legumain-KO inhibited TLR4/MyD88/NF-κB pathway, which was activated by Aβ1-42 in the hippocampus. In conclusion, our results suggested that legumain-KO reduced the level of neuroinflammation that was associated with inhibiting TLR4/MyD88/NF-κB pathways, thereby improving the hippocampal synaptic plasticity and reducing the cognitive impairments in Aβ1-42-treated mice. Legumain knockout blocked microglia activation by inhibiting TLR4/MyD88/NF-κB signaling pathways, and further reduced inflammatory cytokine expression. As a result, legumain knockout alleviated synaptic damage and cognitive impairment induced by Aβ1--42.


International consultation on incontinence questionnaire - Urinary incontinence short form ICIQ-UI SF: Validation of its use in a Danish speaking population of municipal employees.
Worldwide, the estimated prevalence of urinary incontinence is 8.7%. Urinary incontinence is more frequent in women than in men. Posing the right questions is crucial, when diagnosing urinary incontinence, but also to evaluate the need of treatment and treatment effect. Therefore, reliable and validated questionnaires within this area are needed. Even though the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) has been used on a daily basis in the Danish Urogynaecological Database since 2006, it has not yet been validated in a Danish population of both men and women. To test the reliability and validity of the Danish version of the ICIQ-UI SF in a Danish speaking population of men and women among municipal employees. Content validity was evaluated with semi-structured interviews. A quantitative field test was performed, in which the questionnaire was distributed electronically to municipal workers by E-mail. Statistical methods included item characteristics (missings, kurtosis and skewness), internal consistency (Chronbach's alfa), test-retest (ICC), construct validity (known group validation), and floor and ceiling effect. A number of 1814 Danish municipal workers completed the questionnaire. Of the total number of responders, 426 were invited to complete the questionnaire twice (for test-retest) and 215 (50.5%) of these completed the questions again two weeks later. Statistical analyses of the ICIQ-UI SF demonstrated no floor and ceiling effects, skewness was zero and kurtosis 0.00-0.49. Cronbach's alfa was 0.87 and intraclass correlation coefficient 0.73. Two out of three hypotheses were accepted in the known-groups validation. This study offers an adaptation of the ICIQ-UI SF to a Danish setting. The Danish ICIQ-UI SF demonstrated acceptable reliability and validity. However, clinicians should consider the relatively high measurement error.


A new class of bacterial quorum sensing antagonists: glycomonoterpenols synthesized using linalool and alpha terpineol.
With increasing burden of antibiotic resistant microorganism search for newer drug targets and potent drug molecules is a never ending scenario. Quorum sensing (QS), the phenomenon of bacterial cross-talk, is one such target that has captured the attention of many and has been touted as the future of new age antimicrobials. Quorum sensing has the potential to regulate a plethora of bacterial virulence phenotypes and search of molecules with powerful quorum sensing inhibitory (QSI) capacity are underway. Monoterpene alcohols like linalool and alpha terpineol have been shown to possess antimicrobial and anti-biofilm activity. However in this article we attempt to bring forth a new class of compounds, glycomonoterpenols, derived from monoterpenoids alcohols. These glycomonoterpenols have been synthesized using Candida bombicola ATCC 22214 by feeding the cells with linalool and alpha terpineol respectively as substrates in 10% glucose, production medium. The advantage of these molecules over their parent compound is their additional surfactant like property, increased solubility and enhanced QSI potential. A variety of gram-negative bacteria capable of elaborating quorum sensing mediated phenotypes have been selected and both these glycoterpenoid derivatives have been shown to possess strong anti-QS activity.


Epidemiological dynamics of SARS-CoV-2 VOC Gamma in Rio de Janeiro, Brazil.
The emergence and widespread circulation of severe acute respiratory syndrome coronavirus 2 variants of concern (VOCs) or interest impose an enhanced threat to global public health. In Brazil, one of the countries most severely impacted throughout the pandemic, a complex dynamics involving variants co-circulation and turnover events has been recorded with the emergence and spread of VOC Gamma in Manaus in late 2020. In this context, we present a genomic epidemiology investigation based on samples collected between December 2020 and May 2021 in the second major Brazilian metropolis, Rio de Janeiro. By sequencing 244 novel genomes through all epidemiological weeks in this period, we were able to document the introduction and rapid dissemination of VOC Gamma in the city, driving the rise of the third local epidemic wave. Molecular clock analysis indicates that this variant has circulated locally since the first weeks of 2021 and only 7 weeks were necessary for it to achieve a frequency above 70 per cent, consistent with rates of growth observed in Manaus and other states. Moreover, a Bayesian phylogeographic reconstruction indicates that VOC Gamma spread throughout Brazil between December 2020 and January 2021 and that it was introduced in Rio de Janeiro through at least 13 events coming from nearly all regions of the country. Comparative analysis of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) cycle threshold (Ct) values provides further evidence that VOC Gamma induces higher viral loads (N1 target; mean reduction of Ct: 2.7, 95 per cent confidence interval = ± 0.7). This analysis corroborates the previously proposed mechanistic basis for this variant-enhanced transmissibility and distinguished epidemiological behavior. Our results document the evolution of VOC Gamma and provide independent assessment of scenarios previously studied in Manaus, therefore contributing to the better understanding of the epidemiological dynamics currently being surveyed in other Brazilian regions.


Biomarkers in sepsis.
There is much enthusiasm and interest in sepsis biomarkers, particularly because sepsis is a highly lethal condition, its diagnosis is challenging, and even simple treatment with antibiotics has led to serious adverse consequences such as emergence of resistant pathogens. Yet development of a sepsis biomarker requires many more steps than simply finding an association between a particular molecule and a clinical state or outcome. Demonstration of improvement of therapeutic practice using receiver-operating characteristic and other analyses is important. Validation in independent, prospective and, preferably, multicenter trials is essential. Many promising candidate sepsis biomarkers have recently been proposed. While procalcitonin (PCT) is currently the most studied sepsis biomarker, evidence of potential value has been found for a wide array of blood biomarkers including proteins, mRNA expression in whole blood or leukocytes, micro-RNAs (miRNA), pathogen and host DNA, pathogen and host genetic variants and metabolomic panels, and even in the novel use of currently available clinical data. While the most common early reports link putative sepsis biomarker levels to severity of illness and outcome (prognostic), this is not anticipated to be their primary use. More important is the distinction between infection and noninfectious inflammatory responses (diagnostic) and the use of sepsis biomarkers to direct therapy (predictive).


ETEC regulates GPR109A expression in intestinal epithelial cells mediated by inflammatory factors secreted by macrophages.
Gut microbes control host immunity and homeostasis, and their abnormal changes are associated with the occurrence and development of diseases. GPR109A is an essential receptor on intestinal epithelial cells and interacts with gut microbes. Moreover, increased Enterotoxigenic Escherichia coli K88 strain colonization promotes GPR109A expression in vivo. This study evaluated the detailed mechanism of pathogenic bacteria promoting GPR109A expression. The results revealed that ETEC K88 indirectly fosters GPR109A expression in intestinal epithelial cells by stimulating the production of IL-1β and TNF-α through macrophages which are mediated by ERK1/2 pathway. The study explains the molecular mechanisms by which the bacteria regulate the homeostasis of the host intestinal gene expression during ETEC infection.


The NLRP3 inflammasome is dispensable for ER stress-induced pancreatic β-cell damage in Akita mice.
Uncontrolled endoplasmic reticulum (ER) stress activates members of the NOD-like receptor family, which are involved in the pyrin domain containing 3 (NLRP3) inflammasome pathway. This pathway has been proposed to contribute to β-cell dysfunction and death. However, the connection between ER stress and NLRP3 inflammasome activation remains controversial. Here we generated Akita/KO (Ins2(+/C96Y); NLRP3(-/-)) mice by crossing Akita (Ins2(+/C96Y); NLRP3(+/+)) mice with NLRP3 KO (Ins2(+/+); NLRP3(-/-)) mice. We then compared the metabolic phenotypes of the different strains. Knockout of the NLRP3 inflammasome did not affect the onset or the severity of diabetes in Akita/KO mice at any point of the study. Histological observations of pancreatic islets supported these findings. Tunicamycin-exposed islets from NLRP3 KO mice exhibited similar levels of ER stress and apoptosis induction as islets from WT (Ins2(+/+); NLRP3(+/+)) mice. Furthermore, NLRP3 deletion did not prevent tunicamycin-mediated reduction of glucose-stimulated insulin secretion. In conclusion, deletion of the NLRP3 inflammasome did not protect against ER stress-induced diabetes development or β-cell damage, indicating that β cell death in Akita mice is not mediated via activation of the NLRP3 inflammasome.


Atypical plasmacytoid monomorphic adenoma of salivary glands of the tongue: cytologic, histologic, immunohistochemical, and ultrastructural findings.
We describe the case of an 11-yr-old boy with a 2.5-cm-diameter soft tumor superficially located at the dorsal aspect of the tongue. Fine-needle aspiration cytology smears showed plump epithelioid cells with round to mildly oval nuclei and open chromatin. One or two nucleoli of intermediate size were noticed in each nucleus. These cells appeared singly or in small groups. The findings were interpreted as containing plasmacytoid cells coming from an adenoma of salivary gland origin. The histologic examination of the surgical specimen revealed noncohesive, pleomorphic polygonal cells combining plasmacytoid/rhabdoid cytoplasmic features, with mild to moderate nuclear pleomorphism. One mitotic figure was observed per 10 high-power fields. Immunoreactivity was strongly positive for vimentin and S-100 protein, less intense for the cytokeratins, and negative for smooth muscle actin, muscle-specific actin, myoglobin, and GFAP. No ultrastructural evidences of myogenous differentiation were found. We propose that this case represents an unusual atypical variant of plasmacytoid monomorphic adenoma.


Analysis of Defense-Related Gene Expression and Leaf Metabolome in Wheat During the Early Infection Stages of Blumeria graminis f. sp. tritici.
Blumeria graminis f. sp. tritici (Bgt) is an obligate biotrophic fungal pathogen responsible for powdery mildew in bread wheat (Triticum aestivum). Upon Bgt infection, the wheat plant activates basal defense mechanisms, namely PAMP-triggered immunity, in the leaves during the first few days. Understanding this early stage of quantitative resistance is crucial for developing new breeding tools and evaluating plant resistance inducers for sustainable agricultural practices. In this sense, we used a combination of transcriptomic and metabolomic approaches to analyze the early steps of the interaction between Bgt and the moderately susceptible wheat cultivar Pakito. Bgt infection resulted in an increasing expression of genes encoding pathogenesis-related (PR) proteins (PR1, PR4, PR5, and PR8) known to target the pathogen, during the first 48 h postinoculation. Moreover, RT-qPCR and metabolomic analyses pointed out the importance of the phenylpropanoid pathway in quantitative resistance against Bgt. Among metabolites linked to this pathway, hydroxycinnamic acid amides containing agmatine and putrescine as amine components accumulated from the second to the fourth day after inoculation. This suggests their involvement in quantitative resistance via cross-linking processes in cell walls for reinforcement, which is supported by the up-regulation of PAL (phenylalanine ammonia-lyase), PR15 (oxalate oxidase) and POX (peroxidase) after inoculation. Finally, pipecolic acid, which is considered a signal involved in systemic acquired resistance, accumulated after inoculation. These new insights lead to a better understanding of basal defense in wheat leaves after Bgt infection.


Effects of various steroids on in vitro lifespan and cell growth of human fetal lung fibroblasts (WI-38).
Human fetal lung fibroblasts, WI-38, were cultivated in a medium containing various steroids. A dose-response curve constructed by counting the number of cells on day 16, or at regular intervals, showed that glucocorticoids (hydrocortisone and cortisone) and mineralocorticoids (aldosterone and deoxycorticosterone) caused an increase in cell density when added at physiological concentrations or higher. On the other hand, androgens (testosterone, dihydrotestosterone, and dehydroepiandrosterone), estrogen (17 beta-estradiol), and progesterone caused a decrease in cell density at higher concentrations (5 micrograms/ml, or more) although these had no effect on cell density at concentrations lower than 0.5 micrograms/ml. With cells grown from population doubling 31 in a medium containing steroids, it was shown that hydrocortisone extended the in vitro lifespan of WI-38 cells at concentrations of both 5 micrograms/ml and 0.5 micrograms/ml, while dehydroepiandrosterone, 17 beta-estradiol, and progesterone caused a shortening in lifespan at only 5 micrograms/ml. These results suggest that there is a direct relationship between the effects of steroids on cell growth and the lifespan of human fetal lung fibroblasts.


VEGF differentially regulates transcription and translation of ZO-1alpha+ and ZO-1alpha- and mediates trans-epithelial resistance in cultured endothelial and epithelial cells.
Tight junctions (TJ) between retinal pigmented epithelial (RPE) and retinal endothelial cells maintain the outer and inner blood-retinal barrier, and the breakdown of these barriers is associated with retinal diseases. Vascular endothelial growth factor (VEGF) increases vascular permeability and is thought to be involved in age-related maculopathy. However, to date, little is known about the effect of VEGF on RPE cell junctions. We have investigated the effect of VEGF on TJ formation by examining two essential proteins, ZO-1alpha(+) and ZO-1alpha(-). Cultured vascular endothelial cells in the presence of 5 ng/ml VEGF significantly down-regulate ZO-1alpha(+) and ZO-1alpha(-) transcripts and proteins with significant loss of their trans-epithelial resistance (TER). Immunoconfocal analysis with an anti-ZO-1 antibody has confirmed the relocation of ZO-1 protein from membrane to cytoplasm. By contrast, in the presence of 5 ng/ml VEGF, cultured RPE cells (ARPE19 and RPE51) significantly up-regulate ZO-1alpha(+) and ZO-1alpha(-) transcripts and proteins resulting in a significant increase in their TER. Subsequent immunoconfocal analysis has demonstrated increased ZO-1 membrane assembly in VEGF-treated RPE cells. Thus, VEGF has a dual capability with respect to the regulation of the expression of some TJ proteins at the transcriptional and post-translational levels depending on cell type.


HCV in serum, peripheral blood mononuclear cells and lymphocyte subpopulations in C-hepatitis patients.
To define the best marker for the follow-up and evaluation of HCV infections we determined anti-HCV antibodies, serum transaminases and HCV RNA in patients diagnosed with chronic hepatitis for C virus and treated with alpha-interferon. The presence/absence of HCV RNA was determined in serum, peripheral blood mononuclear cells (PBMC) and lymphocyte subpopulations. Samples were submitted to RT-PCR and subsequent nested PCR. Treatment with alpha-interferon induced a fall in the number of HCV RNA positive patients from an initial 88 to 25% at the end of the treatment. The withdrawal of treatment was associated with a significant increase in the number of HCV RNA positive patients (43% at the 12-month follow-up). In 61% of the patients the PCR analysis of the PBMC population detected the presence of HCV RNA. In 87% of cases the cell fraction identified as CD19 resulted positive in the PCR test and the viral genome was undetectable in PBMC subpopulations in only 13% of cases. In one third of the patients whose serum was negative for PCR the analysis demonstrated the presence of HCV RNA in PBMC. Conclusions: The disappearance of the viral genome in serum, a criterion of treatment response, is not necessarily followed by its disappearance in PBMC. The joint determination of HCV by PCR technique in serum and blood cells should be used as a particular instrument with each patient.


Monoclonal antibodies against the native or denatured forms of muscarinic acetylcholine receptors.
BALB/c mice were immunized with affinity-purified muscarinic acetylcholine receptors from calf brain and their splenocytes fused with NS1 myeloma cells. Hybrid cultures were grown and selected for production of antibodies on the basis of enzyme immunoassays on calf and rat forebrain membrane preparations. Thirty-four clones were retained and six of them further subcloned. Two of these subclones produced antibodies that selectively recognized muscarinic acetylcholine receptor-bearing membranes. The M-35b antibodies interacted only with native digitonin-solubilized receptors, and not with denatured receptors. The M-23c antibodies did not react with active digitonin-solubilized receptors but recognized the denatured form. The M-23c antibodies should thus be useful in the purification of the receptor and its precursor translation products, while the M-35b antibodies could be used for the immunocytochemical localization of the receptor in cells and tissues of different species.


Study of the insulin dimerization: binding free energy calculations and per-residue free energy decomposition.
A calculation of the binding free energy for the dimerization of insulin has been performed using the molecular mechanics-generalized Born surface area approach. The calculated absolute binding free energy is -11.9 kcal/mol, in approximate agreement with the experimental value of -7.2 kcal/mol. The results show that the dimerization is mainly due to nonpolar interactions. The role of the hydrogen bonds between the 2 monomers appears to give the direction of the interactions. A per-atom decomposition of the binding free energy has been performed to identify the residues contributing most to the self association free energy. Residues B24-B26 are found to make the largest favorable contributions to the dimerization. Other residues situated at the interface between the 2 monomers were found to make favorable but smaller contributions to the dimerization: Tyr B16, Val B12, and Pro B28, and to an even lesser extent, Gly B23. The energy decomposition on a per-residue basis is in agreement with experimental alanine scanning data. The results obtained from a single trajectory (i.e., the dimer trajectory is also used for the monomer analysis) and 2 trajectories (i.e., separate trajectories are used for the monomer and dimer) are similar.


Comparison of counterimmunoelectrophoresis and latex particle agglutination in the detection of Streptococcus pneumoniae in blood cultures.
Blood cultures from 140 patients with chest infections were examined for the presence of pneumococcal antigen by both latex particle agglutination and counterimmunoelectrophoresis. Twenty-three samples (15 patients) were positive for pneumococcal antigen by counterimmunoelectrophoresis, of which 21 samples (13 patients) yielded Streptococcus pneumoniae in culture. Thirty-three samples (20 patients) were positive by latex particle agglutination, of which 24 samples (15 patients) were culture positive. The sensitivities and specificities were calculated and it was concluded that latex particle agglutination was the better test for the determination of the presence of pneumococcal capsular polysaccharide.


A new assay for the genetic study of general anesthesia in Drosophila melanogaster: use in analysis of mutations in the X-chromosomal 12E region.
We describe a new measure of the influence of general anesthetics on Drosophila that uses the robust tendency of fruit flies to briskly walk upwards after being tapped down. We expose flies to a fixed concentration of anesthetic gas in a 50 ml tube for a period of up to 1 h and then test the distribution of flies in the tube shortly after tapping them to its bottom. By measuring the effect of a series of anesthetic concentrations on the fraction of flies that fail to climb, we derive quantitative descriptors of the potency of the drug. This "distribution test" is superior to previous assays of anesthetic potency in terms of ease and reliability. We have used the assay to further the genetic analysis of several mutations that cluster on the X chromosome and are known to influence both neural function and anesthesia sensitivity. The results establish complementation patterns between the mutations, refine their genetic map positions, and open the way for the molecular identification of the relevant gene(s).


Nicotine dependence and associated factors among persons who use electronic e-cigarettes in Malaysia - an online survey.
Nicotine dependence, factors associated with dependence, and self-reported side effects among people who use e-cigarettes are scarce in developing countries. A sample of 302 persons who currently use e-cigarettes was recruited from discussion forums on Reddit, Facebook, and the forum 'lowyat'. The online Google form survey collected data on demographics, e-cigarette use, and the reasons, for cigarette smoking, Fagerstorm Test for Nicotine Dependence adapted for e-cigarettes (eFTND), and side effects experienced. The mean age was 25.5 years (6.5), 60.6% were males and 86% had higher education. About 47% were using e-cigarettes only, 27.8% were currently using dual products (both electronic and conventional cigarettes), and 25.2% had also smoked cigarettes in the past. 'Less harmful than cigarettes' (56.3%), 'because I enjoy it' (46.7%), and 'it has a variety of flavors (40.4%) were the common reasons for e-cigarette use. The mean eFTND score was 3.9 (SD = 2.2), with a median of four side effects (IQR 3-6), sore or dry mouth/throat (41.4%), cough 33.4%, headache (20.5%), dizziness (16.2%) were commonly reported side effects. eFTND score and side effects were higher among persons using dual products. By multiple linear regression analysis, males (β = 0.56 95% CI 0.45, 1.05, p = 0.033), dual-use (β = 0.95 95% CI 0.34, 1.56, p < 0.003), and use of nicotine-containing e-cigarettes (β = 0.66 95% CI 0.07, 1.25 p = 0.024) had higher eFTND score. Our findings of the study call for the placement of disclaimers about possible nicotine addiction and side effects of e-cigarette products.


Primary pancreatic leiomyosarcoma: a case report.
Leiomyosarcoma are malignant tumours of the soft tissues. It is most commonly found in the stomach, small intestine and retroperitoneum. Primary pancreatic leiomyosarcoma is extremely rare and only 22 cases have been reported in the literature since 1951. Its prognosis is poor and the palliative treatment is only aimed at symptomatic improvement. We report case of primary pancreatic leiomyosarcoma with liver metastases in a 73 year old man who presented with weight loss, epigastric pain, anorexia, abdominal fullness and obstructive jaundice. Histological examination and Immunohistochemical analysis of liver biopsy specimen confirmed the diagnosis of metastatic leiomyosarcoma. The patient died of disease 3 months after the initial diagnosis. Leiomyosarcoma of the pancreas is an extremely rare malignancy with a poor prognosis. Treatment is aimed at symptomatic improvement and pain management.


Study of amino and sulfhydryl sites in the sodium pathway in dog red blood cell membranes.
Amino reactive TNBS (2,4,6-trinitrobenzene sulfonic acid). SITS (4-acetamido-4'-isothiocyano-stilbene-2-2' -disulfonic acid), and Zn++, and SH reactive Hg++ were employed to study sodium channels in dog red blood cells. Simultaneous modification of the membrane with both a SH and an amino modifier results in an increase in Na+ permeability which is equal to the sum of their individual effects. This indicates that SH and amino sites are separate units. Three lines of evidence indicate that the amino sites are more superficial than the SH sites. (1) Pretreatment with an amino modifer decreases the effectiveness of subsequent SH modification. (2) SITS, a nonpenetrating amino reagent, enhances Na+ permeability while DTNB, a nonpenetrating SH modifier, is ineffective. (3) Pretreatment of amino sites decreases the apparent affinity of Hg++ for SH sites. In addition, three lines of evidence indicate that TNBS and Zn++ modify different amino sites. First, simultaneous modification with TNBS and Zn++ results in an increase in Na+ permeability equal to the sum of their individual effects. Secondly, Zn++ causes an increase in Na+ permeability in cells previously treated with TNBS. Finally, the pH dependence of Zn++ modification is oposite that for TNBS modification. These pH experiments suggest than Zn++ enhances Na+ permeability by reacting with unprotonated amino sites while TNBS modifies protonated amino sites. It is concluded that the sodium permeability of dog red blood cells is normally limited by superficial amino sites and deeper slfhydryl sites in the sodium channels.


Comparative analysis of QS3D versus droplet digital PCR for quantitative measures of EGFR T790M mutation from identical plasma.
The capacity of QuantStudio™ 3D (QS3D) and droplet digital PCR (dPCR) for the detection of plasma Epidermal Growth Factor Receptor (EGFR) mutations have been widely reported. Few comparative studies on the quantitative test of the identical DNA material, however, are carried out. Here we compared the performance of the two methods in detecting EGFR T790M mutation in cell-free DNA (cfDNA) from the same lung cancer patients. We recruited 72 non-small cell lung cancer (NSCLC) patients who initially respond to tyrosine kinase inhibitor treatment but subsequently developed resistance. Two tubes of 10mL anticoagulant blood were collected and cfDNA was isolated from plasma. Identical cfDNA samples were analyzed for T790M mutation using QS3D and droplet dPCR in parallel. T790M mutation was detected in 15 and 21 cfDNA samples by QS3D and droplet digital PCR, respectively. The 6 discordant samples showed low mutation abundance (∼0.1%) and the discrepancy is caused by the stricter threshold settings for QS3D dPCR. The overall agreement between the two methods was 91.7% (66/72). The median allele frequencies for QS3D dPCR and droplet dPCR to detect T790M mutation was 2.01% and 2.62%, respectively. There was no significance in mutation abundance detected by both methods. Both methods are highly correlated with allele frequencies and copy numbers in T790M wild type and mutant, with R2 of 0.98, 0.92 and 0.95, respectively. Our study demonstrated that QS3D dPCR are highly consistent with droplet PCR for quantitative determination of EGFR T790M mutation in plasma cfDNA.


Good neighbors.
A new method for investigation of genome-wide DNA methylation allows the discovery of epigenetic modifications in tumor as well as surrounding stromal cells.


Prevalence of Mycoplasma haemofelis, 'Candidatus Mycoplasma haemominutum', Bartonella species, Ehrlichia species, and Anaplasma phagocytophilum DNA in the blood of cats with anemia.
Hemoplasmas are known causes of anemia in some cats and some Bartonella species have been associated with anemia in people and in dogs. In this retrospective study, we used polymerase chain reaction (PCR) assays to determine the prevalence rates of Mycoplasma haemofelis, 'Candidatus M haemominutum', A phagocytophilum, Ehrlichia species, and Bartonella species DNA in the blood of cats with anemia and a control group of healthy cats. DNA of the organisms was amplified from 22 of 89 cats with anemia (24.7%) and 20 of 87 healthy cats (23.0%). DNA of a hemoplasma was amplified from 18 of 89 cats with anemia (20.2%) and 13 of 87 healthy cats (14.9%); DNA of a Bartonella species was amplified from five of 89 cats with anemia (5.6%) and seven of 87 healthy cats (8.0%). There were no statistically significant differences detected between groups.


Risks associated with intraaortic balloon pumping in patients with and without diabetes mellitus.
Between 1967 and 1982, intraaortic balloon pumping (IABP) was attempted in 733 patients. Of these, 132 were diabetic: 51 patients were managed with diet alone, 46 patients took oral hypoglycemic agents and 35 patients required insulin. Vascular complications associated with IABP occurred in 34% of the insulin-dependent diabetics, in 18% of other diabetics and in 14% of nondiabetic patients. Infectious complications were 37, 22 and 25%, respectively. Seventy-five diabetic patients (57%) were discharged alive from the hospital after balloon pumping, essentially the same proportion as among nondiabetic patients (58%). It is concluded that although diabetics incur a higher complication rate, IABP is not contraindicated.


Primary syphilis presenting as a painful unilateral inguinal lymphadenopathy, without cutaneous manifestations, in a 71-year-old Japanese man: A case report.
Syphilitic infection is usually observed in young patients, and the first stage of the disease (primary syphilis) is characterized by painless cutaneous and lymph node lesions. Herein, we describe a 71-year-old Japanese man with primary syphilis that presented as unilateral inguinal lymphadenopathy without skin lesions. Originally, an incarcerated hernia was clinically suspected. The lymph node pathologically showed suppurative lymphadenitis with vague granulomas; immunohistochemistry was highly suggestive of a syphilitic infection. Primary syphilis was confirmed by positive serological tests. Syphilitic infection should be included in the clinicopathological differential diagnoses for patients with inguinal lymphadenopathy, even in elderly patients without skin lesions.


Treatment of advanced Hodgkin's disease with chemotherapy and irradiation. Controlled trial of two versus three alternating, potentially non-cross-resistant drug combinations.
From January 1979 to June 1983, 71 evaluable, previously untreated patients with advanced Hodgkin's disease completed a randomized trial of two or three potentially non-cross-resistant drug combinations and low-dose radiotherapy to initially involved nodal regions (2,000 to 3,000 rads). All patients received nine cycles of alternating chemotherapy regimens and radiotherapy between cycles 6 and 7. Thirty-four patients received three combinations: lomustine, melphalan, vindesine (CAD), MOPP, and doxorubicin, bleomycin, vinblastine (ABV). The complete remission rate was 82 percent, partial remission rate 12 percent, and progression rate 6 percent. There were two relapses from complete remission and three deaths. Thirty-seven patients received MOPP and ABV plus dacarbazine (D). The complete remission rate was 78 percent, partial remission rate 16 percent, and progression rate 6 percent, with three relapses from complete remission and five deaths. Myelosuppression was more frequent with CAD/MOPP/ABV/radiotherapy, and nausea and vomiting with MOPP/ABVD/radiotherapy. The results for both are among the best reported, and CAD/MOPP/ABV/radiotherapy was more acceptable to patients.


Blood flow in the peripheral vestibular system.
A quantitative estimation of the vestibular blood flow was made in normal rabbits using the microsphere method. The total inner ear blood flow was 4 mg per minute, the cochlear blood flow was 3 mg per minute, and the vestibular blood flow was 1 mg per minute.


An efficient CRISPR-based strategy to insert small and large fragments of DNA using short homology arms.
We previously reported a CRISPR-mediated knock-in strategy into introns of Drosophila genes, generating an attP-FRT-SA-T2A-GAL4-polyA-3XP3-EGFP-FRT-attP transgenic library for multiple uses (Lee et al., 2018a). The method relied on double stranded DNA (dsDNA) homology donors with ~1 kb homology arms. Here, we describe three new simpler ways to edit genes in flies. We create single stranded DNA (ssDNA) donors using PCR and add 100 nt of homology on each side of an integration cassette, followed by enzymatic removal of one strand. Using this method, we generated GFP-tagged proteins that mark organelles in S2 cells. We then describe two dsDNA methods using cheap synthesized donors flanked by 100 nt homology arms and gRNA target sites cloned into a plasmid. Upon injection, donor DNA (1 to 5 kb) is released from the plasmid by Cas9. The cassette integrates efficiently and precisely in vivo. The approach is fast, cheap, and scalable.


[On the accumulation of tonsillectomies in young females].
The clinical observation of an accumulation of tonsillectomies in young women raises two questions: (1) Can this observation be proved statistically? and, if yes, (2) are there any hints as to a possible psychological reason of this phenomenon? A total of 24 young females (15-20 years old) admitted to the ENT-department for tonsillectomy were given a preoperative personality screening using the Freiburger personality inventory (FPI-R). A significant, sex specific accumulation of tonsillectomies was found in females aged 10-20 years. The personality screening revealed a significant increase of the subscales "social orientation" and "aggressivity" in the entire group. Eight out of the 24 females showed an abnormal personality profile with statistically unexpected correlations between the subscales "somatic complaints", "excitability" and "aggressivity". In spite of the low sample size, these results suggest that in some young females in the postadolescent age group, an abnormal personality structure influences the indication of tonsillectomy.


Identifying components in consent information needed to support informed decision making about trial participation: An interview study with women managing cancer.
Research governance requires patients give informed consent to participate in clinical trials. However, there are concerns that consent information may not support patient participation decisions. This study investigates the utility of consent information in supporting women's trial participation decisions when receiving treatment for cancer. An interview study with women receiving cancer treatments at a medical oncology outpatient clinic in Yorkshire (UK). All women over 18 years, not admitted to a hospital ward and who had currently or previously been invited to take part in a trial were invited to take part in the study over a three month period. Interviews were audio-tape recorded, transcribed and analysed using thematic analysis. Of those eligible (n = 41), 21 women with breast (n = 11), ovarian (n = 8) and endometrial (n = 2) cancer participated (mean age = 57 years). Eighteen had made at least one trial decision and three were considering taking part in a trial. Findings are synthesised under two analytical themes: 1) Influence of the cancer and cancer treatment context on decision making for trial participation; and 2) Experiences of the consenting process and their influence on decision making. Designing trial information to represent explicitly the trial participation decision as being between standard care and study-related care options is more likely to effectively support patients in making informed decisions between standard care treatments and taking part in a trial.


Behavioral effects of chronic lead exposure in the adult rat.
Adult rats fed daily rations of laboratory chow laced with lead acetate, were tested for operant (schedule-controlled) responding and conditioned suppression. In Experiment 1, animals receiving 10 mg/kg lead showed significantly lower operant response rates (lever pressing) than controls. Conditioned suppression performance was not different between the two groups. During retraining that followed a 42 day no-training period, lead-treated subjects showed greater percent of prior baseline responding than controls. The groups were not different on a test for stimulus control or an appetitive resistance to extinction test. In Experiment 2, separate lead-treated groups were chronically exposed to either 10 mg/kg, 5 mg/kg, or 1 mg/kg lead daily. Behavioral tests showed that while the lowest lead level (1 mg/kg) occasioned higher rates of operant lever pressing relative to controls, the highest level (10 mg/kg) again produced lower rates. On a retraining task administered after an interpolated 90 day no-training period, the two highest exposure groups were significantly above controls regarding percent of baseline responding and there was evidence that the 5 mg/kg group was significantly superior to controls in terms of absolute response rate. No differences in conditioned suppression or resistance to extinction were observed in the second experiment.


Calcium-channel blockers in the treatment of migraine.
According to classic theory, a migraine attack is initiated by cerebrovascular spasm followed by extracranial vasodilatation. Results of recent studies support this theory and suggest that cerebral blood flow during the initial phase of migraine symptoms is, in fact, decreased and this decrease probably leads to ischemia and hypoxia. Cellular hypoxia, in turn, can cause an increase in the flow of calcium from the extracellular fluid to the intracellular space, resulting in calcium overload and cellular dysfunction. Because calcium-channel blockers selectively inhibit the intracellular influx of calcium ions, investigators have begun evaluating the efficacy of these agents for migraine prophylaxis. Nimodipine, a calcium-channel blocker that exhibits selective effects on cerebral vessels, seems to offer protection against the cerebral ischemia and hypoxia presumed to be operative during migraine attacks. In a double-blind, placebo-controlled study, nimodipine decreased the frequency and duration of migraine attacks by at least half in 69% of patients treated with this agent. Comparable reductions in migraine frequency and duration were attained in 58, 51, 41 and 52% of patients treated with methysergide maleate, pizotifen, clonidine hydrochloride and propranolol, respectively. The piperazine derivative flunarizine also has calcium-channel blocking properties. This agent prevents vasospasm in cerebral arteries and protects against cerebral hypoxia. Results of double-blind studies of migraine prophylaxis with flunarizine demonstrate the beneficial effects of this agent, particularly in younger patients. Flunarizine proved to be superior to pizotifen in decreasing the severity of migraine attacks and comparable to pizotifen in decreasing their frequency.(ABSTRACT TRUNCATED AT 250 WORDS)


Outcomes and prognostic variables of extracranial germ cell tumors in children and adolescents treated over a decade: A developing world perspective.
The purpose of this single-center study was to analyze the outcomes of extracranial germ cell tumors (GCTs) in children treated on a multimodality regimen. Retrospective study of children (<18 years) with a histopathologically confirmed diagnosis of extracranial GCT over a period of 10 years (January 2009 to December 2018) treated on a uniform institution-based protocol consisting of both cisplatin- and carboplatin-based regimens. All completely excised teratomas and stage I gonadal tumors received no further therapy (low risk [LR]); stage IV ovarian, stage III-IV extragonadal GCTs received six cycles of chemotherapy (high risk [HR]), and the remaining received four cycles of chemotherapy (intermediate risk [IR]). A total of 297 children were treated with a female:male ratio of 1.72:1 and median age of 4 years. Forty-three children had pure teratomas. Gonadal GCTs (N = 180) were more common than extragonadal GCTs (N = 117) with ovary as primary site in 128 children (43%) and sacrococcygeal site being the commonest extragonadal location (N = 41; 14%). LR, IR, and HR disease were noted in 60 (20.2%), 125 (42%), and 112 (37.8%) patients, respectively. Three-fourths of ovarian tumors and half of testicular tumors operated prior to presentation needed upstaging. Forty-one patients relapsed and 43 children expired (disease-related: 33; toxic deaths: 9; unknown: 1). The 5-year event-free survival (EFS)/overall survival (OS) of malignant GCT (n = 254) was 72.50%/82.70%, respectively, with gonadal site (p = .001), LR and IR (p = .001) and nonmetastatic disease (p = .001) being favorable prognostic variables. The LR and IR GCTs in our cohort had an excellent outcome. A significant proportion of IR gonadal GCTs can be spared of systemic chemotherapy by adhering to strict surgical guidelines. In HR GCTs however, intensifying therapies to improve outcomes must be balanced against the risk of cumulative toxicity, more so in a resource-limited setting.


Spatial coverage of water hyacinth (Eichhornia crassipes (Mart.) Solms) on Lake Tana and associated water loss.
The introduction of water hyacinth poses a serious threat to economic viability of Lake Tana and its environments. This study aimed to capture the spatial coverage of water hyacinth and its effect on water loss in Lake Tana using quantitative research methods. Four satellite images representing each season of 2019 were downloaded from USGS. In addition, pan evaporation data were taken from the National Meteorological Agency. ArcGis 10.4, Envi 5.3, Qgis 3.12.1 plug in CSP and Excel used to manage land use land cover classification and water loss estimation analysis. The seasonal coverage of water hyacinth was 15.35, 4.14, 11.82 and 13.59 km2 in winter, autumn, summer and spring 2019 respectively representing 0.63 and 0.17 percent of the Lake as a maximum and minimum coverage. The mean daily evaporation of Lake Tana was 5.14 mm/day, but this increased to 18.85 mm/day due to the presence of water hyacinth. The mean net daily water loss due to water hyacinth at Lake Tana was 0.14 km2 while 52,62 km3 in 2019. The study concludes that water hyacinth caused enormous negative impact on the water volume reduction in Lake Tana. Management of the Lake Tana environment and control of the water hyacinth weed are recommended to sustain the Lake.


Mutational and expression analysis of ELIP1 and ELIP2 in Arabidopsis thaliana.
Plants exposed to photoinhibitory conditions respond by accumulation of the early light-induced proteins (ELIPs) with a potential photoprotective function. In Arabidopsis thaliana two genes (Elip1 and Elip2) encode for two ELIP proteins: evidence exists that the two genes are differentially regulated but their precise function is unclear. Mutants null for one or the other Elip gene can help in elucidating ELIPs role and here we describe the expression profile of ELIP1 and ELIP2, and the phenotype of such null mutants. Both ELIPs accumulate during greening of etiolated seedlings and in mature plants the transcripts fluctuate diurnally without protein accumulation. Steady-state transcript level of both genes increases in response to high light with transcription of Elip1 much more sensitive than that of Elip2 to increasing irradiation at 22 degrees C. At 4 degrees C instead Elip2 is strongly transcribed even at growing light. Furthermore, only ELIP1 accumulates under high light at 22 degrees C while both proteins accumulate at 4 degrees C. These results indicate the existence of a differential regulation of ELIPs expression in response to light or chilling stress with mechanisms active either at transcriptional and post-transcriptional level. Phenotypically, the mutants behave as the wild type as far as sensitivity to light- or light and cold-induced short-term photoinhibition, while both ELIPs are necessary to ensure a high rate of chlorophyll accumulation during deetiolation in continuous high light.


Effective and safe reduction of blood pressure with the combination of amlodipine 5 mg and valsartan 160 mg in hypertensive patients not controlled by calcium channel blocker monotherapy.
The addition of an angiotensin II receptor blocker to calcium channel blocker-based antihypertensive therapy may be associated with enhanced efficacy and reduced risk of adverse events. This 8-week, open-label, single-arm trial evaluated the efficacy and tolerability of the combination of amlodipine and valsartan in patients not responding adequately to treatment with amlodipine or felodipine alone. Patients aged > or =18 years with moderate essential hypertension (defined as mean sitting systolic blood pressure [MSSBP] > or =160 and <180 mmHg) were treated for 4 weeks with once-daily amlodipine 5 mg or felodipine 5 mg. At week 4, patients not adequately responding were treated for an additional 4 weeks with once-daily amlodipine 5 mg plus valsartan 160 mg. Of 214 patients treated for 4 weeks with amlodipine 5 mg or felodipine 5 mg, 181 failed to achieve MSSBP <140 mmHg. These non-responders were treated for an additional 4 weeks with amlodipine 5 mg and valsartan 160 mg. A clinically and statistically significant additional reduction in MSSBP of 13.1 mmHg (95% confidence interval [CI]: 11.4, 14.7; P<0.0001) and a mean sitting diastolic blood pressure of 5.3 mmHg (95% CI: 4.3, 6.3; P<0.0001) were observed. Of patients treated with amlodipine 5 mg and valsartan 160 mg, 51.1% achieved target blood pressure levels (<140/90 mmHg) after 4 weeks. Adverse event rates were low in both treatment phases, and most were mild or moderate in severity. The combination of amlodipine/valsartan was effective and well tolerated.


A spatiotemporal land-use regression model of winter fine particulate levels in residential neighbourhoods.
Residential wood burning can be a significant wintertime source of ambient fine particles in urban and suburban areas. We developed a statistical model to predict minute (min) levels of particles with median diameter of <1 μm (PM1) from mobile monitoring on evenings of winter weekends at different residential locations in Quebec, Canada, considering wood burning emissions. The 6 s PM1 levels were concurrently measured on 10 preselected routes travelled 3 to 24 times during the winters of 2008-2009 and 2009-2010 by vehicles equipped with a GRIMM or a dataRAM sampler and a Global Positioning System device. Route-specific and global land-use regression (LUR) models were developed using the following spatial and temporal covariates to predict 1-min-averaged PM1 levels: chimney density from property assessment data at sampling locations, PM2.5 "regional background" levels of particles with median diameter of <2.5 μm (PM2.5) and temperature and wind speed at hour of sampling, elevation at sampling locations and day of the week. In the various routes travelled, between 49% and 94% of the variability in PM1 levels was explained by the selected covariates. The effect of chimney density was not negligible in "cottage areas." The R(2) for the global model including all routes was 0.40. This LUR is the first to predict PM1 levels in both space and time with consideration of the effects of wood burning emissions. We show that the influence of chimney density, a proxy for wood burning emissions, varies by regions and that a global model cannot be used to predict PM in regions that were not measured. Future work should consider using both survey data on wood burning intensity and information from numerical air quality forecast models, in LUR models, to improve the generalisation of the prediction of fine particulate levels.


Outcome of routine histopathological examination of gallbladder specimen following elective laparoscopic cholecystectomy.
Gallstone disease is one of the commonest surgical ailments encountered in our setup. Its prevalence in India varies from 2% to 29%. Although cholelithiasis accounts for more than 95% of gall bladder related disease, routine histopathological examination (HPE) is vital. It reveals a myriad of benign as well as the malignant surgical pathology of the gallbladder (GB). This part of the world is considered as an endemic region for GB carcinoma as well as gallstone disease. This study intends to evaluate the outcome of the routine HPE of laparoscopic cholecystectomy specimens. This retrospective observational study evaluated the results of the routine HPE of elective laparoscopic cholecystectomy specimens of single tertiary care center. Patients suspected or diagnosed with carcinoma gall bladder were excluded. Demographic data such as age, sex, and pathology results were recorded. From January 2017 to December 2019, HPEs of 921 patients who had undergone laparoscopic cholecystectomy specimens were analyzed. 97.6% specimens had benign lesion of which chronic calculus cholecystitis was predominantly high (95.01%) followed by cholesterosis (9.9%) and xanthogranulomatous cholecystitis (6.51%). Incidental carcinoma gall bladder was observed in 17 specimens accounting for 1.85%. Mean age of patients who underwent cholecystectomy was 43.10 ± 13.90 with female to male ratio of 3.23:1. Chronic calculus cholecystitis was the most common gall bladder disease with high female preponderance to all GB pathologies. This study affirms the importance of routine HPE after cholecystectomy as early incidental detection of carcinoma gall bladder alters the postoperative management approach and patients are expected to have a better outcome with it.


Short- and Long-Term Outcomes of Transabdominal Preperitoneal, Open Mesh Plug and Open Tissue Inguinal Hernia Repair.
There have been few comparisons of the postoperative outcomes of transabdominal preperitoneal (TAPP), open mesh plug (mesh plug) and open tissue (tissue) hernia repair. The objectives of this study were to compare these repair methods. This was a retrospective study of 1813 inguinal hernia patients between January 2008 and December 2016. Of these patients, 474 underwent TAPP repair, 1293 underwent mesh plug repair, and 46 underwent tissue repair. The short-term and long-term outcomes determined by questionnaire were compared among the three groups. In addition, risk factors for patient dissatisfaction were assessed. In the TAPP group, the postoperative complications rate was the lowest at 4.6% (7.4% and 6.5% in the mesh plug and the tissue groups, respectively, P = 0.07), and recurrence rate was lower compared to the mesh plug group (0.8% vs. 3.3%, P = 0.002). As long-term outcomes, 92%, 88% and 75% of patients were satisfied in the TAPP, mesh plug and tissue groups, respectively (P = 0.03). The rate of patients with numbness was 3.1% in the TAPP group, 5.2% in the mesh plug group and 14% in the tissue group (P = 0.04). Predictive independent risk factors for patient dissatisfaction were complications (OR: 3.99, 95% CI: 1.35-11.8, P = 0.012) and infection (OR: 16.9, 95% CI: 1.25-229, P = 0.003). TAPP repair is superior to mesh plug and tissue repairs in terms of complications, satisfaction and numbness, as determined by questionnaire. Complications and infection were independently associated with the patient dissatisfaction.


Concurrent and adjuvant temozolomide-based chemoradiotherapy schedules for glioblastoma. Hypotheses based on two prospective phase II trials.
To investigate the impact of nonstandard concomitant temozolomide (TMZ) administration in two prospective phase II studies for glioblastoma (GBM). From October 2000 to June 2008, 104 patients were enrolled in two studies: 25 in RT-TMZ-10.00 and 79 in RT-TMZ-01.04. Adjuvant radiotherapy (RT) was used with a total dose of 59.4 Gy (1.8 Gy/day). Patients received concomitant TMZ (75 mg/m(2)/day) from Monday to Friday during the first and last weeks of RT in the RT-TMZ-10.00 study and from Monday to Friday during all weeks of RT in the RT-TMZ-01.04 trial. Adjuvant TMZ (200 mg/m(2)) was administered for 5 days every 28 days. Median progression-free (PFS) and overall survival (OS) were 9 and 16 months, respectively, with no significant difference between the two groups (p = 0.5 and 0.14, respectively). The 2- and 5-year OS rates were 32 and 3 %, respectively, and similar to those observed with standard treatment regimens. Our data support the hypothesis that adjuvant TMZ is more important than concomitant chemotherapy (CH) and that RT is the more important element of the concomitant treatment schedule.


Use of an HIV-risk screening tool to identify optimal candidates for PrEP scale-up among men who have sex with men in Toronto, Canada: disconnect between objective and subjective HIV risk.
Identifying appropriate pre-exposure prophylaxis (PrEP) candidates is a challenge in planning for the safe and effective roll-out of this strategy. We explored the use of a validated HIV risk screening tool, HIV Incidence Risk Index for Men who have Sex with Men (HIRI-MSM), to identify "optimal" candidates among MSM testing at a busy sexual health clinic's community testing sites in Toronto, Canada. Between November 2014 and April 2015, we surveyed MSM undergoing anonymous HIV testing at community testing sites in Toronto, Canada, to quantify "optimal" candidates for scaling up PrEP roll-out, defined as being at high objective HIV risk (scoring ≥10 on the HIRI-MSM), perceiving oneself at moderate-to-high HIV risk and being willing to use PrEP. Cascades were constructed to identify barriers to broader PrEP uptake. The association between HIRI-MSM score and both willingness to use PrEP and perceived HIV risk were explored in separate multivariable logistic regression analyses. Of 420 respondents, 64.4% were objectively at high risk, 52.5% were willing to use PrEP and 27.2% perceived themselves at moderate-to-high HIV risk. Only 16.4% were "optimal" candidates. Higher HIRI-MSM scores were positively associated with both willingness to use PrEP (aOR=1.7 per 10 score increase, 95%CI=1.3-2.2) and moderate-to-high perceived HIV risk (aOR=1.7 per 10 score increase, 95%CI=1.2-2.3). The proportion of men who were "optimal" candidates increased to 42.9% when the objective HIV risk cut-off was changed to top quartile of HIRI-MSM scores (≥26). In our full cascade, a very low proportion (5.3%) of MSM surveyed could potentially benefit from PrEP under current conditions. The greatest barrier in the cascade was low perception of HIV risk among high-risk men, but considerable numbers were also lost in downstream cascade steps. Of men at high objective HIV risk, 68.3% did not perceive themselves to be at moderate-to-high HIV risk, 23.6% were unaware of PrEP, 40.1% were not willing to use PrEP, 47.6% lacked a family physician with whom they felt comfortable discussing sexual health, and 31.6% had no means to cover the cost of PrEP. A higher HIRI-MSM cut-off may be helpful for identifying candidates for PrEP scale-up. Improving engagement in the PrEP cascade will require interventions to simultaneously address multiple barriers.


Adult-onset Still's disease successfully treated with Chinese herbal medicine: A case report with 15-month follow-up.
Adult-onset Still's disease (AOSD) is a rare but clinically well-known, polygenic, and systemic autoinflammatory disease, which is characterized by spiking fever, evanescent skin rash, arthralgia, and sore throat. The application of non-steroidal anti-inflammatory drugs and glucocorticoids, which are first-line therapies of AOSD, is limited due to their side effects such as liver injury or disorder of blood glucose. Therefore, patients who suffer from systemic diseases in China prefer to seek help from Chinese herbal medicine (CHM), which is an important part of complementary and alternative medicine. In this case, we report a 28-year-old male badminton coach presenting with a 15-day history of fever and skin rash, accompanied by sore throat, fatigue, myalgia and chills. Additionally, hepatosplenomegaly, multiple lymphadenopathies, aminotransferase abnormality, and elevated inflammatory factor levels were observed during hospitalization. Infectious diseases, solid tumors, hematological diseases, and common autoimmune diseases were excluded. Not benefitting from antibiotic therapy, the patient was finally diagnosed with AOSD, after a careful examination, then showed rapid remission after a six-week treatment with CHM granules based on Xiaochaihu Decoction and Yinqiao Powder. After stopping the treatment, there was no relapse within a 15-month follow-up period. To the best of our knowledge, this is the first well-documented case of this successful treatment. The present case report suggests that CHM is a reliable choice for complementary and alternative therapy for AOSD, but confirming the utility of CHM for AOSD requires further support from prospective studies.


A retrospective study (2001-2017) of acute and chronic morbidity and mortality associated with Staphylococcus aureus bacteraemia in a tertiary neonatal intensive care unit.
Staphylococcus aureus bacteraemia (SAB) in NICU patients can cause significant morbidity and mortality. To review early and late neonatal SAB with regard to risk factors, treatment, acute complications and long-term outcomes. A retrospective study of laboratory confirmed SAB over a 16-year period (November 2001-January 2017) in a tertiary neonatal unit in Ireland. A total of 74 neonates (MSSA n = 72, MRSA n = 2) were identified; 8.1% (n = 6) early sepsis, 91.8% (n = 68) late sepsis. Low birth weight neonates (born weighing less than 2500 g) 80% (n = 59). Median age to bacteraemia 11 days post-delivery (range = 0-100 days); median onset early sepsis 1.5 days versus late sepsis 12 days. Complications of SAB; cellulitis n = 17, pneumonia n = 12, necrotising enterocolitis n = 7, thromobophlebitis n = 5, skin abscess formation n = 4, osteomyelitis n = 3, endocarditis n = 1. Late SAB mortality 6.4% (n = 3). Preterm and low birth weight infants were at highest risk of SAB. Only a small proportion of affected children had long-term clinical sequelae on follow-up. The high rate of recurrence and breakthrough bacteraemia suggests that early implementation of a targeted anti-staphylococcal antimicrobial regimen may be of particular benefit.


The economics of non-attendance and the expected effect of charging a fine on non-attendees.
Non-attendance is claimed to waste substantial health care resources. However, this is only vaguely supported by empirical evidence. The epidemiology of non-attendees is explored in a rather large number of studies along with a sizeable number of studies documenting the effectiveness of various interventions to reduce non-attendance rates. Very few studies include more than one intervention and very few report information on the cost of the intervention which enables only vague conclusions about the cost-effectiveness of the interventions. The effectiveness of charging a fine on non-attendees, which has recently been suggested in Denmark and United Kingdom, has been studied in very few studies. These studies reveal that a fine will as most economists expected reduce the non-attendance rate. The literature of non-attendance discloses an immense need for studies addressing the non-attendance problem applying economic theory and standards of analysis.


The prognostic utility of dihomo-gamma-linolenic acid (DGLA) in patients with acute coronary heart disease.
We previously investigated the prognostic utility of red blood cell (RBC) n-3 fatty acids (FAs) in survivors of an acute myocardial syndrome (ACS) but found no relationship with all-cause mortality and cardiac death or MI after two years. Here we extend our follow-up to 7years, focusing on the potential predictive power of RBC n-6 FAs. We included 398 ACS patients presenting with increased troponin-T (TnT) levels for whom baseline RBC FA data were available. Cox regression analysis was used to relate the risk of future events to RBC n-6 FA levels, both continuously and by quartile. At 7-year follow-up, 183 (46.0%) had died, 128 (32.2%) had experienced another MI and 24 (6.0%) had had a stroke. Death or MI occurred in 227 patients (57.0%); and death, MI or stroke in 235 patients (59.0%). In a multivariable Cox regression model for total death, the hazard ratio (HR) in the highest as compared to the lowest quartile of dihomo-γ-linolenic acid (DGLA) was 0.55 [95% confidence interval (CI), 0.35-0.88, p=0.012, for death or MI [HR 0.62 (95% CI, 0.41-0.94), p=0.025], and for the fully combined endpoint [HR 0.57 (95% CI, 0.38-0.86), p=0.006]. Similar results were found in the per 1-SD analysis. No other RBC n-6 FAs significantly predicted these outcomes in multivariable models. RBC DGLA levels had significant independent prognostic value in post-ACS patients. These findings need confirmation, and the possible biochemical pathways by which higher DGLA membrane levels may be cardioprotective should be explored.


[Electronic device for determining motor activity].
The authors present a short description and the principal scheme of an electron apparatus for the determination of the motor activity of laboratory animals. This apparatus is based on the principle of recording the changes in volume occurring during the movement of animals.


Modified dagger-tip Sheets glide to facilitate 2-point fixation across the anterior chamber in aniridic aphakic eyes.
Presented is a modified technique for removing a failed endothelial allograft in an aniridic aphakic eye that reduces the risk of posterior dislocation. This technique involves the creation of an artificial iris plane using a Sheets glide by trimming it into the shape of a dagger so that it can be pulled through the anterior chamber and fixated by both its passage through a paracentesis incision and the main incision. The Sheets glide then acts as a physical barrier, or scaffold, to allow safe removal of the failed endothelial allograft and subsequent repeat endothelial keratoplasty while avoiding posterior dislocation of the tissue into the vitreous cavity.


Case Report: Opsoclonus-Myoclonus Syndrome Associated With Contactin-Associated Protein-Like 2 and Acetylcholine Receptor Autoantibodies in the Setting of Non-Small Cell Lung Carcinoma.
Opsoclonus myoclonus syndrome (OMS) is a rare immune-mediated paraneoplastic or para/-post-infectious syndrome characterized by "dancing" eye movements, myoclonus, and ataxia. Neuropsychiatric symptoms have also been reported. Without treatment, OMS may progress to further neurological impairment and even death. Autoimmune attack of CNS structures in OMS is most commonly mediated by anti-Ri (also known as ANNA2) IgG antibodies, with additional findings implicating antibodies targeting various neurotransmitter receptors. Prompt immunotherapy and neoplasm treatment may result in improvement. We report a novel association of Contactin-Associated Protein-Like 2 (Caspr2) antibodies occurring in association with paraneoplastic OMS. While breast cancer and small cell lung cancer (SCLC) are more commonly associated with OMS among adults, we characterize a novel association between Caspr2 antibody in a patient with mixed non-small cell and small cell lung carcinoma.


The lower expression of circulating miR-210 and elevated serum levels of HIF-1α in ischemic stroke; Possible markers for diagnosis and disease prediction.
Stroke, either due to ischemia or hemorrhage, causes acute neurological damages to the brain. There is shortage of reliable biomarkers for ischemic stroke (IS), and we therefore investigated the serum concentrations of microRNA-210 (miR-210) and hypoxia inducible factor-1α (HIF-1α), as possible diagnostic and/or prognostic markers for IS. Serum samples were acquired from 52 IS patients and their healthy counterparts at five time points: upon admission, 24 and 48 h after admission, upon discharge and 3 months later. Serum levels of miR-210 and HIF-1α were respectively analyzed using real time RT-PCR and ELISA. Diagnostic and prognostic accuracy tests were performed to assess the value of suggested biomarkers. IS patients demonstrated higher levels of serum HIF-1α and lower miR-210 in comparison to the healthy subjects. MiR-210 was suggested to be a weak diagnostic biomarker at the time of admission (AUC = 0.61; p = 0.05), while HIF-1α was an acceptable diagnostic marker for IS (AUC = 0.73; p < 0.0001). The higher expression of miR-210 and lower levels of HIF-1α were associated with better survivals in IS patients. Serum miR-210 is a weak diagnostic marker of IS. Serum HIF-1α is a better biomarker in diagnosing IS patients but further work in larger groups, including those with hemorrhagic stroke is necessary to confirm its diagnostic utility. Similarly, the prognostic potentiality of miR-210 and HIF-1α was acceptable but needs bigger sample size and longer follow-up to be statistically confirmed.


Challenges in health service delivery under public-private partnership in Tanzania: stakeholders' views from Dar es Salaam region.
Public-private partnership in the health sector was introduced to improve the delivery of health services in Tanzania. Contrary, the expected outcomes have not been fully realised. This study aimed at investigating challenges encountered in implementing public-private partnership institutional arrangements in health service delivery in Kinondoni Municipality, Dar es Salaam, Tanzania. A qualitative case study design was employed, where in-depth interviews with stakeholders were held and document reviews conducted. Fourteen (n = 14) participants engaged in this study. Eight (n = 8) and six (n = 6) of the fourteen participants were from the public and private sector respectively. The thematic approach was used to analyse data, and ethical principles in the research process were upheld. Findings revealed that although public-private partnerships are hailed for supplementing the government's efforts in the provision of health services, institutional arrangements for the smooth provision of these services are lacking. Several challenges encumber smooth provision of health services and these include inadequate resources, ineffective monitoring and evaluation, and insufficient consultations between partners. Inadequate legal and policy framework, or ineffective implementation practices may influence challenges facing institutional arrangements for public-private partnerships. Therefore, strengthening of public-private partnerships is recommended to improve implementation mechanisms and practices such as adherence to partnership agreements and compliance to the policies, laws and regulations.


[Duration of the mitotic cycle at the period of synchronous cleavage division (t0) in the starfish Asterina pectinifera (Müller et Troschel)].
The duration of a single division (tau 0) in a period of synchronous cleavage, time of development before the start of cleavage, and rotation, hatching and gastrulation stages in A. pectinifera at different temperatures were estimated. The range of temperatures optimal for embryonic and early larval development of the starfish was determined.


A new look at low-dose aspirin: Co-administration with tamoxifen in ovulation induction in anovulatory PCOS women.
To evaluate the efficacy of co-administration of low-dose aspirin (LDA) and tamoxifen on ovulation rates, endometrial thickness and clinical pregnancy rates in anovulatory PCOS women. A randomized clinical trial was conducted among 188 anovulatory PCOS women at Suez Canal University Hospitals, Ismailia - Egypt. Patients were divided into 2 groups. The study group received a daily oral dose of 81 mg of LDA, while the control group received placebo (oral vitamin B12 tablets). Both groups started tamoxifen 10 mg twice daily from 3rd day to 7th day of the cycle. Folliculometry was performed by transvaginal sonography every other day starting from the 9th day of the cycle. Human Chorionic Gonadotrophin 5000 I.U. was given I.M. when at least one dominant follicle was present. The outcome measures included the number of mature follicles (≥18 mm in diameter), endometrial thickness and appearance in addition to the clinical pregnancy rates. The mean number of follicles per patient was significantly more in the study group (1.4 ± 0.8 vs. 1.1 ± 0.4; p value=<0.05). In addition, the endometrium was significantly thicker on study group (9.6 ± 1.4 mm vs. 7.8 ± 1.2 mm; p value=<0.01). Significantly, the pregnancy rate was more in the study compared to the control group (37.2% vs. 22.3% respectively; p value=<0.03). Co-administration of LDA with tamoxifen significantly improves ovarian response to stimulation, endometrial thickness and pregnancy rates in anovulatory PCOS patients. This combination is an effective, cheap and safe protocol for infertile PCOS women undergoing ovulation induction.


Acetabular Rim Ossification Variants Are Found in Almost 20% of Patients Presenting With Hip Pain.
To determine the prevalence of 4 different types of acetabular rim ossifications, including partial labral ossification or punctate calcification, true os acetabuli, acetabular rim stress fracture, and complete labral ossification, and to determine whether different types of periacetabular ossifications are linked to demographic or radiological factors. We retrospectively reviewed the medial records of patients presenting for hip-related complaints at 2 sports medicine practices from September 2007 to December 2009. An anteroposterior radiograph of both hips and a lateral radiograph of each hip was obtained for all patients and reviewed for findings of cam and pincer femoroacetabular impingement, degenerative changes (Tönnis grade), and periacetabular calcifications for both hips. These parameters were also evaluated with respect to symptoms, sex, and age. Four hundred ninety-one consecutive patients (982 hips) presented to 2 orthopaedic surgeons at 2 centers for "hip"-related complaints. There were 223 males and 268 females (age 39 ± 14 years). The overall prevalence of periacetabular calcifications in hips was 17.6%, with 56.6% of calcifications in the symptomatic hip and 43.4% in the contralateral hip. Four basic patterns of calcification were identified: punctuate calcifications within the labrum (8.0% hips), large rounded calcifications (os acetabuli) (4.2% hip), large fragments with a vertical line of the superior-lateral acetabular rim, consistent with healed or non-healed stress fracture (2.0% hips), and complete ossification of the labrum (3.4% hips). Overall, male sex (P = .002), increased lateral center-edge angle (P = .046), and higher Tönnis grade (P < .001) statistically predicted the presence of periacetabular ossification. Punctate calcifications were more prevalent in males (P = .002). Higher Tönnis grade (P = .029) and increased alpha angle (P = .046) were more prevalent with os acetabuli. Younger age (P = .001), male sex (P = .048), increased alpha angle (P = .012), and increased lateral center-edge angle (P < .001) were more prevalent in acetabular rim fractures. No factors were statistically significant at predicting the presence of an ossified labrum. Periacetabular calcifications are not uncommon. Four particular patterns of calcification are identified: punctate labral calcifications (8%), larger rounded calcifications (i.e., os acetabuli) (4.2%), acetabular rim stress fractures (2%), and complete ossification of the labrum (3.4%) for a combined prevalence of 17.6% in patients presenting to an orthopaedic surgeon with "hip"-related complaints. Nearly half were in the asymptomatic hip. Male sex had a higher prevalence of periacetabular calcifications. An increased lateral center edge angle and higher Tönnis grade also had a higher prevalence of periacetabular calcifications. Younger male patients are more likely to have acetabular rim stress fractures. Patients with an increased alpha angle have a higher prevalence of os acetabuli and rim stress fractures. This study aims to identify, quantify, and categorize periacetabular calcifications about the hip. Their clinical relationships and relevance have been discussed, but no study has distinctly categorized the various types and their prevalence. This study provides a framework for identification and categorization.


Total synthesis and biological evaluation of potent analogues of dictyostatin: modification of the C2-C6 dienoate region.
By exploiting a Still-Gennari olefination of a common C11-C26 aldehyde with a C4-C10 or C1-C10 beta-ketophosphonate, three modified C2-C6 region analogues of the 22-membered macrolide dictyostatin were synthesised and evaluated in vitro for growth inhibition against a range of human cancer cell lines, including the Taxol-resistant NCI/ADR-Res cell line. 6-Desmethyldictyostatin and 2,3-dihydrodictyostatin displayed potent (low nanomolar) antiproliferative activity, intermediate between dictyostatin and discodermolide, while 2,3,4,5-tetrahydrodictyostatin showed activity comparable to discodermolide. As with dictyostatin, these simplified analogues act through a mechanism of microtubule stabilisation, G2/M arrest and apoptosis.


Development of a high performance liquid chromatography tandem mass spectrometry based analysis for the simultaneous quantification of various Alternaria toxins in wine, vegetable juices and fruit juices.
An analytical method based on high performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS) detection for the simultaneous quantification of 12 Alternaria toxins in wine, vegetable juices and fruit juices was developed. Excellent chromatographic performance was demonstrated for tenuazonic acid (TeA) in a multi-analyte method. This comprehensive study is also the first to report the determination of TeA, alternariol (AOH), alternariol monomethyl ether (AME), tentoxin (TEN) and altenuene (ALT), altertoxin I (ATX-I), altertoxin II (ATX-II), altenuisol (ATL), iso-altenuene (isoALT), altenuic acid III (AA-III) and the AAL toxins TB1 und TB2 in samples from the German market. Several types of HPLC columns were tested for the liquid chromatographic separation of the toxins of interest that widely differ in their polarities. The focus was on gaining suitable retention while avoiding derivatization steps especially for TeA and AA-III. Three atmospheric pressure ionization techniques used with liquid chromatography (electrospray, chemical and photo ionization) were tested to obtain the best selectivity and sensitivity. Samples were diluted with sodium hydrogen carbonate buffer and extracted on a diatomaceous earth solid phase extraction cartridge. Method validation was carried out by using tomato juice, citrus juice and white wine as blank matrices. Limits of detection ranged from 0.10 to 0.59μgL(-1) and limits of quantification ranged from 0.4-3.1μgL(-1) depending on the toxin and matrix. Recoveries were around 100±9% for all toxins except stemphyltoxin III (STTX-III) and altenusin (ALS) due to instability during sample clean up. Matrix-induced effects leading to ion suppression especially for ATX-I, ATX-II and AA-III were investigated. Relative standard deviations of repeatability (RSDr) and intermediate reproducibility (RSDR) were ≤9.3 and ≤17.1, respectively, for the toxins in different matrices at levels of 5 and 30μgL(-1). Finally, 103 commercially obtained wine and juice samples from the German market in 2015 were analysed. TeA was found most frequently (68% of all analysed samples) in concentrations of up to 60.0μgL(-1). AOH, AME and TEN were detected in fewer samples (37%, 16% and 30%) at lower concentrations of up to 8.2, 1.5 and 10.3μgL(-1), respectively. AA-III and ATL were detected for the first time in 3% and 17% of food all samples, in concentrations of up to 6.0μgL(-1) and 5.9μgL(-1), respectively.