Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study.
Persistent pulmonary hypertension (PPHN) occurs in as many as 6.8 of 1000 live births. Mortality is approximately 10% to 20% with high-frequency ventilation, surfactant, inhaled nitric oxide, and extracorporeal membrane oxygenation but is much higher when these therapies are not available. Sildenafil is a phosphodiesterase inhibitor type 5 that selectively reduces pulmonary vascular resistance. Our goal was to evaluate the feasibility of using oral sildenafil and its effect on oxygenation in PPHN. This study was a proof-of-concept, randomized, masked study in infants >35.5 weeks' gestation and <3 days old with severe PPHN and oxygenation index (OI) >25 admitted to the NICU (Hospital Niño Jesús, Barranquilla, Colombia). The sildenafil solution was prepared from a 50-mg tablet. The first dose (1 mg/kg) or placebo was given by orogastric tube <30 minutes after randomization and every 6 hours. Preductal saturation and blood pressure were monitored continuously. OI was calculated every 6 hours. The main outcome variable was the effect of oral sildenafil on oxygenation. Sildenafil or placebo was discontinued when OI was <20 or if there was no significant change in OI after 36 hours. Six infants with an OI of >25 received placebo, and 7 received oral sildenafil at a median age of 25 hours. All infants were severely ill, on fraction of inspired oxygen 1.0, and with similar ventilatory parameters. Intragastric sildenafil and placebo were well tolerated. In the treatment group, OI improved in all infants within 6 to 30 hours, all showed a steady improvement in pulse oxygen saturation over time, and none had noticeable effect on blood pressure; 6 of 7 survived. In the placebo group, 1 of 6 infants survived. Oral sildenafil was administered easily and tolerated as well as placebo and improved OI in infants with severe PPHN, which suggests that oral sildenafil may be effective in the treatment of PPHN and underscores the need for a large, controlled trial.


Evaluation of Salud Para Su Corazón (Health for your Heart) -- National Council of La Raza Promotora Outreach Program.
In 2001, the National Heart, Lung, and Blood Institute partnered with the National Council of La Raza to conduct a pilot test of its community-based outreach program Salud Para Su Corazón (Health for Your Heart), which aims to reduce the burden of morbidity and mortality associated with cardiovascular disease among Latinos. The effectiveness of promotores de salud (community health workers) in improving heart-healthy behaviors among Latino families participating in the pilot program at seven sites was evaluated. Data on the characteristics of the promotores in the Salud Para Su Corazón program were compiled. Promotores collected data on family risk factors, health habits, referrals and screenings, information sharing, and program satisfaction from 223 participating Latino families (320 individual family members) through questionnaires. Paired t tests and chi-square tests were used to measure pretest-posttest differences among program participants. Results demonstrated the effectiveness of the promotora model in improving heart-healthy behaviors, promoting community referrals and screenings, enhancing information sharing beyond families, and satisfying participants' expectations of the program. The main outcome of interest was the change in heart-healthy behaviors among families. The community outreach model worked well in the seven pilot programs because of the successes of the promotores and the support of the community-based organizations. Successes stemmed in part from the train-the-trainer approach. Promotoria, as implemented in this program, has the potential to be integrated with a medical model of patient care for primary, secondary, and tertiary prevention.


Role of Topotecan in Non-Small Cell Lung Cancer: A Review of Literature.
Topotecan (TPT), a chemotherapeutic agent, is a topoisomerase-I inhibitor. Topoisomerase-I is a nuclear enzyme that relieves torsion strain in DNA by opening single strand breaks which helps in DNA replication. TPT inhibits this enzyme, thus preventing DNA replication and causes cell death. TPT has demonstrated to have broad spectrum of antitumor activity in tumors like cervical, ovarian, endometrial and small cell lung cancers (SCLCs). The intravenous (IV) formulation of the drug is currently approved by the US Food and Drug Administration for the treatment of patients with SCLC and ovarian cancer at a dose of 1.5 mg/m2 administered daily for five consecutive days, with treatment cycles repeated every 3 weeks. TPT has shown some promising activity in the treatment of non-small cell lung cancer (NSCLC) with favorable side effect profile. Several clinical trials have been conducted with TPT in either IV or oral formulation for the treatment of NSCLC as a first or second-line treatment. Here we reviewed all the clinical trials done with TPT to date in the treatment of NSCLC both as a single-agent and combination therapy.


[Bisphosphonate-associated osteonecrosis of the jaws 1].
Bisphosphonates are generally administered either orally or intravenously. Orally administered bisphosphonates are primarilly used in the treatment of postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, and Paget's disease. When orally administered, only about 1% is absorbed from the tractus from the tractus digestivus. With intravenous administration, higher blood levels levels are reached. Intravenously administered bisphosphonates are used in the treatment of hypercalcaemia, Kahler's disease, and bone metastases of other malignancies. A few cases of osteonecrosis of the jaw(s) are seen especially when more powerful bisphosphonates are administered intravenously. This osteonecrosis is most often provoked by means of an invasive oral treatment. Bisphosphonate-associated osteonecrosis is very difficult to treat. Therefore, dental preventive measures and treatment of dental foci and other inflammations are recommended before starting bisphosphonate therapy.


Optimized, unequal pulse spacing in multiple echo sequences improves refocusing in magnetic resonance.
A recent quantum computing paper (G. S. Uhrig, Phys. Rev. Lett. 98, 100504 (2007)) analytically derived optimal pulse spacings for a multiple spin echo sequence designed to remove decoherence in a two-level system coupled to a bath. The spacings in what has been called a "Uhrig dynamic decoupling (UDD) sequence" differ dramatically from the conventional, equal pulse spacing of a Carr-Purcell-Meiboom-Gill (CPMG) multiple spin echo sequence. The UDD sequence was derived for a model that is unrelated to magnetic resonance, but was recently shown theoretically to be more general. Here we show that the UDD sequence has theoretical advantages for magnetic resonance imaging of structured materials such as tissue, where diffusion in compartmentalized and microstructured environments leads to fluctuating fields on a range of different time scales. We also show experimentally, both in excised tissue and in a live mouse tumor model, that optimal UDD sequences produce different T(2)-weighted contrast than do CPMG sequences with the same number of pulses and total delay, with substantial enhancements in most regions. This permits improved characterization of low-frequency spectral density functions in a wide range of applications.


A general coverage theory for shotgun DNA sequencing.
The classical theory of shotgun DNA sequencing accounts for neither the placement dependencies that are a fundamental consequence of the forward-reverse sequencing strategy, nor the edge effect that arises for small to moderate-sized genomic targets. These phenomena are relevant to a number of sequencing scenarios, including large-insert BAC and fosmid clones, filtered genomic libraries, and macro-nuclear chromosomes. Here, we report a model that considers these two effects and provides both the expected value of coverage and its variance. Comparison to methyl-filtered maize data shows significant improvement over classical theory. The model is used to analyze coverage performance over a range of small to moderately-sized genomic targets. We find that the read pairing effect and the edge effect interact in a non-trivial fashion. Shorter reads give superior coverage per unit sequence depth relative to longer ones. In principle, end-sequences can be optimized with respect to template insert length; however, optimal performance is unlikely to be realized in most cases because of inherent size variation in any set of targets. Conversely, single-stranded reads exhibit roughly the same coverage attributes as optimized end-reads. Although linking information is lost, single-stranded data should not pose a significant assembly liability if the target represents predominantly low-copy sequence. We also find that random sequencing should be halted at substantially lower redundancies than those now associated with larger projects. Given the enormous amount of data generated per cycle on pyro-sequencing instruments, this observation suggests devising schemes to split each run cycle between twoor more projects. This would prevent over-sequencing and would further leverage the pyrosequencing method.


Interaction between proteolytic strains of Lactococcus lactis influenced by different types of proteinase during growth in milk.
The influence of the type of cell envelope-located proteinase (PI versus PIII) on the associative growth of Lactococcus lactis in milk was studied. Two genetically engineered strains, differing only by the type of proteinase, were first used as a model study. An interaction occurred during the second exponential growth phase of the mixed culture and resulted in a decrease in growth rate of the PI-type proteinase strain, whereas that of the PIII-type proteinase strain remained unaffected. The reduction in proteolytic activity of the PI-type proteinase strain (presumably resulting from an inhibition of the synthesis of the enzyme) due to the peptides released by the PIII-type proteinase was found to be partly responsible for this interaction. Extension of the study to wild-type proteinase-positive L. lactis strains showed a systematic imbalance of the mixture of the two strains in favor of the PIII-type proteinase strain.


Laser-induced microstructuring of two-dimensional layered inorganic-organic perovskites.
Non-contact bi-directional micropatterning of two-dimensional (2D) layered inorganic-organic (IO) perovskite [(R-NH3)2PbI4, R = organic moiety] thin films by direct laser writing (DLW) has been reported. These 2D materials are in the form of natural multiple quantum well (MQW) structures and show excitonic luminescence at room temperature because of quantum and dielectric confinement effects. Systematic optical and structural analyses of these laser processed hybrid systems provide an insight into laser-matter interaction and a pathway to develop technology to define complex 2D material based devices with new functionalities. These laser-matter interaction studies reveal several concurrent processes: single photon absorption, material ablation, melting and agglomeration of nanostructures and chemical/physical modifications. This study also provides an insight into chemical and optical changes in laser processed 2D perovskites which subsequently can be recovered by chemical processing. Apart from controllable feature sizes, the prolonged laser exposure results in material agglomeration in the form of nano-pillars at the laser track boundaries. Low-cost micro/nano-scaffolding of IO perovskites may have several important advantages in scalable optoelectronic devices, the realisation of luminescent photonic architectures (photonic crystals and waveguides), and light harvesting elements for IO LEDs and solar cells.


Serum vitamin D level alterations in retinal vascular occlusions.
To evaluate serum vitamin D levels in sub-types of retinal vascular occlusions and compare the levels in ischemic and non-ischemic presentations. This study included 50 patients of retinal vascular occlusions comprising central retinal vein occlusion, branch retinal vein occlusion, central retinal artery occlusion, branch retinal artery occlusion (study group) diagnosed on basis of clinical characteristics as well as investigations and an age and gender-matched healthy control group (control group). The study group was further classified into ischemic and non-ischemic subtypes and serum vitamin D levels were analysed and compared. There were 50 patients of various sub-types of retinal vascular occlusions comprising 13 cases of CRVO, 30 cases of BRVO, 05 cases of CRAO, 02 cases of BRAO and 50 age and sex-matched controls. Mean BCVA and CMT in RVO patients was +1.12 log MAR, 346.72 ± 27.93 µm while in control group was +0.37 log MAR, 236.22 ± 3.71 µm which were statistically significant (p = 0.004; p = 0.002). The mean serum vitamin D value in study group was 18.39 ng/dl as compared to 32.31 ng/dl in control group which was statistically significant (p = 0.001). The difference in the baseline vitamin D value between the ischemic and non -ischemic sub groups among total vascular occlusion was found to be statistically significant (p = 0.010). However, baseline vitamin D levels difference among ischemic and non-ischemic cases in individual sub-types of vascular occlusion was statistically insignificant. High prevalence of low serum vitamin D levels is seen in patients of retinal vascular occlusion spectrum diseases. Moreover, ischemic types of retinal vascular occlusion have significantly lower serum vitamin D levels as compared to non - ischemic despite having fewer no of patients in arterial occlusion sub-types. Therefore, vitamin D supplements may be considered as possible future targeted therapy in optimizing the severity of disease.


Design of an Interactive Web Application for Teaching Uncertainty Interpretations of Clinical Tests.
Assessing the uncertainty of diagnostic findings is essential for advising patients. Previous research has demonstrated the difficulty of computing the expected correctness of positive or negative results, although clinical decision support (CDS) tools promise to facilitate adequate interpretations. To teach the potential utility of CDS tools to medical students, we designed an interactive software module that computes and visualizes relevant probabilities from typical inputs. We reviewed the literature on recommended graphical approaches and decided to support contingency tables, plain table formats, tree diagrams, and icon arrays. We implemented these functions in a single-page web application, which was configured to complement our local learning management system where students also access interpretation tasks. Our technical choices promoted a rapid implementation. We intend to explore the utility of the tool during some upcoming courses. Future developments could also model a more complex clinical reality where the likelihood of alternative diagnoses is estimated from sets of clinical investigations.


Starch granulomatosis of the peritoneum.
Starch glove powder is used extensively by surgeons in Britain and is generally considered innocuous so that precautions to prevent granuloma formation, previously taken when talc glove powder was in use, are now neglected. Reported here are five cases of starch granulomatosis of the peritoneum occurring over a period of a few months. This condition requires reoperation within a limited time for its diagnosis and may be confused macroscopically with disseminated malignant disease or tuberculosis or may simply cause adhesions. Recognition is dependent on a high degree of suspicion by both surgeon and histopathologist, as special histological techniques may be necessary. Consequently, it is only in a minority of the florid cases that a diagnosis is made, and the condition would appear to be much more common than is generally realized. A plea is made for scrupulous care to avoid starch powder contamination of the operative field.


Immune complex formation impairs the elimination of solutes from the brain: implications for immunotherapy in Alzheimer's disease.
Basement membranes in the walls of cerebral capillaries and arteries form a major lymphatic drainage pathway for fluid and solutes from the brain. Amyloid-β (Aβ) draining from the brain is deposited in such perivascular pathways as cerebral amyloid angiopathy (CAA) in Alzheimer's disease (AD). CAA increases in severity when Aβ is removed from the brain parenchyma by immunotherapy for AD. In this study we investigated the consequences of immune complexes in artery walls upon drainage of solutes similar to soluble Aβ. We tested the hypothesis that, following active immunization with ovalbumin, immune complexes form within the walls of cerebral arteries and impair the perivascular drainage of solutes from the brain. Mice were immunized against ovalbumin and then challenged by intracerebral microinjection of ovalbumin. Perivascular drainage of solutes was quantified following intracerebral microinjection of soluble fluorescent 3kDa dextran into the brain at different time intervals after intracerebral challenge with ovalbumin. Ovalbumin, IgG and complement C3 co-localized in basement membranes of artery walls 24 hrs after challenge with antigen; this was associated with significantly reduced drainage of dextran in immunized mice. Perivascular drainage along artery walls returned to normal by 7 days. These results indicate that immune complexes form in association with basement membranes of cerebral arteries and interfere transiently with perivascular drainage of solutes from the brain. Immune complexes formed during immunotherapy for AD may similarly impair perivascular drainage of soluble Aβ and increase severity of CAA.


Shared decision-making in primary care: tailoring the Charles et al. model to fit the context of general practice.
To explore the application of the original Charles et al. model of shared treatment decision-making [Charles C, Gafni A, Whelan T. Shared decision-making in the medical encounter: what does it mean? (or it takes at least two to tango). Soc Sci Med 1997;44:681-92; Charles C, Gafni A, Whelan T. Decision-making in the physician-patient encounter: revisiting the shared treatment decision-making model. Soc Sci Med 1999;49:651-61] in the context of general practice, and to determine whether the model needs tailoring for use in this clinical context. Conceptual paper, presenting the defining characteristics of general practice compared to the original clinical context for which the model was developed (i.e. life threatening disease with different treatment options), and exploring how the model can be tailored for use in the context of general practice. We identify two areas where the original model requires tailoring: sharing the decision-making around agreeing on an agenda for each consultation; and adapting the information transfer component of the model to acknowledge that doctors may not be the only, or even the main, source of technical information for patients. Finally, we explore the importance of shared decision-making in the context of chronic disease. The Charles et al. model can be tailored for use in general practice. Tailoring the model for use in general practice has implications for research, in terms of identifying the additional physician competencies needed for implementation. Policy makers who wish to promote shared decision-making need to ensure that incentives which prioritize access and health outcomes do not militate against shared decision-making in general practice.


Solid state conformations and antidopaminergic effects of remoxipride hydrochloride and a closely related salicylamide, FLA 797, in relation to dopamine receptor models.
The X-ray structures of two new 2,6-disubstituted benzamides, i.e., remoxipride hydrochloride monohydrate [-)-(S)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,6-dimethoxybenza mide hydrochloride monohydrate) and FLA 797 [-)-(S)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-methoxysalicylamide ), have been determined as well as the distribution coefficients. The difference in dopamine receptor blocking activity is discussed in terms of lipophilicity and solid state conformations of the two benzamides. The major difference between the solid state conformations lies in the orientation of the carboxamide moiety. In remoxipride the carbonyl group is oriented almost perpendicularly to the benzene ring, thus preventing the formation of a hydrogen-bonded pseudo-ring between the amide hydrogen and the methoxy group found in other types of o-methoxybenzamides. In FLA 797, however, this pseudo-ring is present in the planar conformation of the salicylamide moiety. This conformation is further stabilized by a hydrogen bond between the phenol group and the carbonyl oxygen. The side chain in remoxipride adopts an extended conformation in contrast to FLA 797, where the side chain has a folded conformation. The crystal structures are related to current topographic dopamine receptor models developed from more rigid antidopaminergic compounds. Based on these comparisons, it is suggested that benzamides having an N-ethyl-2-pyrrolidinylmethyl side chain interact with the receptor in the folded conformation. The binding affinity is thought to be further increased by the planar conformation of the salicylamide moiety present in FLA 797, which permits an efficient pi-pi stacking interaction.


Follow-up study of olfactory deficits, cognitive functions, and volume loss of medial temporal lobe structures in patients with mild cognitive impairment.
At 3 years after diagnosis, the risk of Alzheimer disease (AD) for patients with mild cognitive impairment (MCI) is estimated to be 18% to 30%. To improve treatment of patients at high dementia risk there is a need for a better prediction of the risk for transition from MCI to AD. Olfactory deficits are a hypothetical predictor of conversion form MCI to AD. Furthermore, several studies point at volumetric reduction of medial temporal lobe structures as predictors of conversion form MCI to AD. The primary aim of this study was to evaluate whether investigations of odor deficits in MCI combined with neuropsychological tests and MRI examinations can improve prediction of the development of dementia. Changes in olfactory functions, cognitive functions, and volume of medial temporal lobe structures (hippocampus, parahippocampal gyrus, and amygdala) were evaluated in a 24-month follow-up study in 49 MCI patients and 33 controls. In the MCI group, a prediction of strong cognitive functions deterioration based on poor performance in Olfactory Identification tests shows sensitivity of 57% and specificity of 88%. The test based on cognitive functions only shows a sensitivity of 44%, and 89%, respectively. Combined tests having a criteria of poor olfactory identification performance AND poor results of neuropsychological tests showed a sensitivity of 100% and specificity of 84%. Furthermore, correlation was found between the results of Olfactory Identification tests at baseline and deterioration of cognitive functions at follow up. Odor identification threshold did not appear to be a dementia predictor. A correlation of progress of cognitive function deterioration, odor identification deterioration, and decrease of volume of the hippocampus was also observed. Prediction of MCI to dementia conversion can be improved by supplementing the neuropsychological tests with odor identification tests. A follow up study of hippocampus volume reduction, OI performance and cognitive functions deterioration will further increase prediction accuracy.


Family interactions in adoptive compared to nonadoptive families.
Despite the large and growing numbers of adoptive families, little research describes interactions in families with adopted adolescents. Yet, adopted adolescents' increased risk for adjustment problems, combined with the association between family interactions and adolescent adjustment in nonadoptive families, raises questions about differences in adoptive and nonadoptive family interactions. We compared observed and self-reported family interactions between 284 adoptive and 208 nonadoptive families and within 123 families with 1 adopted and 1 nonadopted adolescent. Adolescents averaged 14.9 years of age. Comparisons were made using analysis of variance incorporating hierarchical linear methods in SAS PROC MIXED to control family-related correlations in the data. Parents and children reported more conflict in adoptive families when compared with nonadoptive families. Families with 1 adopted and 1 nonadopted adolescent reported more conflict between parents and adopted adolescents. Observed parental behavior was similar across adoptive and nonadoptive children although adopted adolescents were less warm and, in families with 2 adopted children, more conflictual than nonadopted adolescents. These findings suggest a need for further investigation of the association between family interactions and adopted adolescent problem behavior.


A systematic review of qualitative studies on factors associated with smoking cessation among adolescents and young adults.
To summarize findings from qualitative studies on factors associated with smoking cessation among adolescents and young adults. We searched Pubmed, Psychinfo, CINAHL, Embase, Web of Science, and SCOPUS databases, as well as reference lists, for peer-reviewed articles published in English or French between January 1, 2000, and November 18, 2020. We used keywords such as adolescents, determinants, cessation, smoking, and qualitative methods. Of 1,724 records identified, we included 39 articles that used qualitative or mixed methods, targeted adolescents and young adults aged 10-24, and aimed to identify factors associated with smoking cessation or smoking reduction. Two authors independently extracted the data using a standardized form. We assessed study quality using the National Institute for Health and Care Excellence checklist for qualitative studies. We used an aggregative meta-synthesis approach and identified 39 conceptually distinct factors associated with smoking cessation. We grouped them into two categories: [1] environmental factors [tobacco control policies, pro-smoking norms, smoking cessation services and interventions, influence of friends and family], and [2] individual attributes [psychological characteristics, attitudes, pre-quitting smoking behavior, nicotine dependence symptoms, other substances use]. We developed a synthetic framework that captured the factors identified, the links that connect them, and their associations with smoking cessation. This qualitative synthesis offers new insights on factors related to smoking cessation services, interventions, and to attitudes about cessation [embarrassment when using cessation services] not reported in quantitative reviews, supplementing limited evidence for developing cessation programs for young persons who smoke. Using an aggregative meta-synthesis approach, this study identified 39 conceptually distinct factors grouped into two categories: environmental factors and individual attributes. These findings highlight the importance of considering both environmental and individual factors when developing smoking cessation programs for young persons who smoke. The study also sheds light on self-conscious emotions towards cessation, such as embarrassment when using cessation services, which are often overlooked in quantitative reviews. Overall, this study has important implications for developing effective smoking cessation interventions and policies that address the complex factors influencing smoking behavior among young persons.


Leiomyoma of the epididymis.
Epididymal leiomyomas are rare intrascrotal neoplasms. It is a slow growing tumour and usually present as an enlarged, painless scrotal mass. A case with an unusual presentation is reported with a review of the possible sonographic findings of this entity and the differential diagnosis of a mass in the epididymis.


HIV related behaviours and attitudes among Chinese men who have sex with men in Hong Kong: a population based study.
This study was conducted in order to determine the prevalence of men having sex with men (MSM) and their HIV related behaviours and attitudes among Chinese men in Hong Kong. A large scale, random, population based, anonymous telephone survey of 14 963 men between the ages of 18-60 was conducted. The overall response rate was approximately 57%. Of the respondents, 4.6% had ever engaged in MSM activity. In the 6 months preceding the survey, 2.0% had engaged in MSM behaviours (active MSM) and 0.5% reported having engaged in anal sex MSM behaviours. Among anal sex MSM, consistent condom use was 42.9% with male non-commercial sex partners and even lower with male commercial sex partners (35.7%). Approximately 11% of anal sex MSM and 4.1% of the non-anal sex MSM had contracted an STD in the last 6 months. The prevalence of HIV testing was only 20.6% among anal sex MSM and 11.9% among non-anal sex MSM. Active MSM in Hong Kong are at high risk of HIV infection. The belief of low vulnerability to HIV is prevalent among active MSM in Hong Kong with only 2.0% believing that their chances of HIV infection as being "very likely."


Energy deficit in parvalbumin neurons leads to circuit dysfunction, impaired sensory gating and social disability.
Parvalbumin-expressing, fast spiking interneurons have high-energy demands, which make them particularly susceptible to energy impairment. Recent evidence suggests a link between mitochondrial dysfunction in fast spiking cortical interneurons and neuropsychiatric disorders. However, the effect of mitochondrial dysfunction restricted to parvalbumin interneurons has not been directly addressed in vivo. To investigate the consequences of mitochondrial dysfunction in parvalbumin interneurons in vivo, we generated conditional knockout mice with a progressive decline in oxidative phosphorylation by deleting cox10 gene selectively in parvalbumin neurons (PV-Cox10 CKO). Cox10 ablation results in defective assembly of cytochrome oxidase, the terminal enzyme of the electron transfer chain, and leads to mitochondrial bioenergetic dysfunction. PV-Cox10 CKO mice showed a progressive loss of cytochrome oxidase in cortical parvalbumin interneurons. Cytochrome oxidase protein levels were significantly reduced starting at postnatal day 60, and this was not associated with a change in parvalbumin interneuron density. Analyses of intrinsic electrophysiological properties in layer 5 primary somatosensory cortex revealed that parvalbumin interneurons could not sustain their typical high frequency firing, and their overall excitability was enhanced. An increase in both excitatory and inhibitory input onto parvalbumin interneurons was observed in PV-Cox10 CKO mice, resulting in a disinhibited network with an imbalance of excitation/inhibition. Investigation of network oscillations in PV-Cox10 CKO mice, using local field potential recordings in anesthetized mice, revealed significantly increased gamma and theta frequency oscillation power in both medial prefrontal cortex and hippocampus. PV-Cox10 CKO mice did not exhibit muscle strength or gross motor activity deficits in the time frame of the experiments, but displayed impaired sensory gating and sociability. Taken together, these data reveal that mitochondrial dysfunction in parvalbumin interneurons can alter their intrinsic physiology and network connectivity, resulting in behavioral alterations similar to those observed in neuropsychiatric disorders, such as schizophrenia and autism.


Senkyunolides reduce hydrogen peroxide-induced oxidative damage in human liver HepG2 cells via induction of heme oxygenase-1.
Rhizoma Chuanxiong is widely used as folk medicine to treat the diseases caused by oxidative stress and inflammation. To delineate the underlying molecular mechanisms, we recently found that Rhizoma Chuanxiong extract significantly induced heme oxygenase-1 (HO-1), an enzyme that degrades intracellular heme into three bioactive products: biliverdin, carbon monoxide and free iron. The anti-inflammatory, antiapoptotic and antiproliferative actions of these products highlight HO-1 as a key endogenous antioxidant and cytoprotective gene. This study was designed to further characterize HO-1 induction of Rhizoma Chuanxiong through bioactivity-guided fractionation. All isolated fractions were assayed for HO-1 induction in human HepG2 cell line at mRNA and protein levels. Based on chromatographic profiling, nuclear magnetic resonance (NMR) and mass spectrometric analysis, the active compounds were identified as senkyunolide-H and its stereoisomer senkyunolide-I. Both senkyunolide isomers inhibited the formation of reactive oxygen species and lipid peroxidation and enhanced the cellular resistance to hydrogen peroxide-induced oxidative damage. Notably, heme oxygenase inhibitor tin protoporphyrin IX (SnPP) significantly suppressed the antioxidant activity of senkyunolide stereoisomers. Thus, this study demonstrated that senkyunolide-H and -I attenuated oxidative damage via activation of HO-1 pathway.


Maternal fuels, diabetic embryopathy: pathomechanisms and prevention.
Congenital malformations remain the major cause of morbidity and mortality among the offspring of women with diabetes. Animal and human studies indicate that these anomalies occur very early in pregnancy and result from derangements of the maternal metabolic fuels which support embryogenesis. The mechanism for induction of dysmorphogenesis in experimental diabetic pregnancy has been shown to include deficiency states of membrane lipids (myoinositol, arachidonic acid, etc.), alteration in the prostaglandin cascade, and the generation of excess free oxygen radicals. These biochemical alterations result in characteristic morphological and molecular changes which are considered to be the basis of diabetic embryopathy. This article not only discusses the pathomechanism, but also reviews both clinical and experimental strategies to prevent diabetes-associated birth defects.


Restriction enzyme kinetics monitored by UV linear dichroism.
The use of linear dichroism (LD) spectroscopy for biological applications has been brought to the forefront recently by our development of thermostated microvolume Couette cells. We present a method for following the digestion of DNA by restriction endonucleases in real time without the use of any extrinsic dyes or labels. This is accomplished using linear dichroism spectroscopy (the differential absorbance of light polarized parallel and perpendicular to the sample orientation axis). The differential absorbance signal depends on the degree of alignment of the molecules. In this case the DNA is aligned by Couette flow (flowing the solution in the annular gap between two concentric cylinders), and we monitor the increase in alignment upon linearization of a circular DNA molecule. In addition, we observe a decrease in alignment upon further digestion and subsequent shortening of the DNA. Ten enzymes were investigated: seven enzymes with a single cut site (EcoRI, KpnI, NdeI, NotI, NruI, SmaI, XbaI), two enzymes with two cut sites (BstZ17I, EagI), and one enzyme with no cut site (ClaI). LD, as implemented in this new assay, is broadly applicable across a wide range of DNA-modifying enzymes and compounds and, as such, is a useful addition to the toolbox of biological characterization.


A Mobile App to Support Clinical Diagnosis of Upper Respiratory Problems (eHealthResp): Co-Design Approach.
The misuse of antibiotics is a global public health issue that fosters bacterial resistance and jeopardizes generational health. The development of validated tools such as web-based courses and mobile apps to enhance clinical decisions in upper respiratory infections is of great importance in reducing the incorrect use of antibiotics in these situations. The aim of this study was to design and prevalidate the interface of a mobile app to assist and provide clinical support in the diagnosis of upper respiratory problems. We aimed to assess the adequacy and usability of the interface of the tool in the belief that it could be beneficial to health care delivery in the clinical decision setting. Using a co-design approach that brought together professionals in interface design and experts in pharmacology and pharmacoepidemiology, the mobile app interface was evaluated through peer review sessions held by interface design professionals on a heuristic survey. The reviewers accessed a high-fidelity interactive mock-up of the interface and filled in a questionnaire to assess the dimensions of layout and visual design and navigation and tasks. The resulting feedback of this evaluation supported the redesign of the primary interface, which was assessed for the second time by 2 of the previously mentioned reviewers. With 4 as the highest score, the interface scored a mean of 3.16 (SD 0.45; median of the means 3.2) for layout and visual design and a mean of 3.43 (SD 0.33; median of the means 3.51) for navigation and tasks, reflecting an overall positive evaluation. The open-ended commentaries allowed us to better understand specific recommendations of the reviewers. Throughout this section, approximately 0.98 comments per parameter were registered, reflecting a high level of effectiveness of the chosen parameters in identifying potential problems. The resultant beta version of the interface, addressing the majority of the detected problems, was further assessed by 2 of the previous reviewers, validating the new design. Future tests with physicians and pharmacists will help assess credibility and user experience dimensions. Our study revealed that the designed interface is easy to interpret and use. Peer reviewers raised important issues that could be easily fixed and positively reassessed. As a result, the study enabled us to produce a new tool for interface usability assessment and a set of recommendations for developing mobile interfaces for clinical decision support systems in the scope of upper respiratory problems.


Hypoxia stimulates degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase through accumulation of lanosterol and hypoxia-inducible factor-mediated induction of insigs.
Endoplasmic reticulum-associated degradation of the enzyme 3-hydroxy-3-methylglutaryl-CoA reductase represents one mechanism by which cholesterol synthesis is controlled in mammalian cells. The key reaction in this degradation is binding of reductase to Insig proteins in the endoplasmic reticulum, which is stimulated by the cholesterol precursor lanosterol. Conversion of lanosterol to cholesterol requires removal of three methyl groups, which consumes nine molecules of dioxygen. Here, we report that oxygen deprivation (hypoxia) slows demethylation of lanosterol and its metabolite 24,25-dihydrolanosterol, causing both sterols to accumulate in cells. In addition, hypoxia increases the amount of Insig-1 and Insig-2 in a response mediated by hypoxia-inducible factor (HIF)-1alpha. Accumulation of lanosterol together with increased Insigs accelerates degradation of reductase, which ultimately slows a rate-determining step in cholesterol synthesis. These results define a novel oxygen-sensing mechanism mediated by the combined actions of methylated intermediates in cholesterol synthesis and the hypoxia-activated transcription factor HIF-1alpha.


The Role of Host Genetic Factors in Coronavirus Susceptibility: Review of Animal and Systematic Review of Human Literature.
The SARS-CoV-2 pandemic raises many scientific and clinical questions. These include how host genetic factors affect disease susceptibility and pathogenesis. New work is emerging related to SARS-CoV-2; previous work has been conducted on other coronaviruses that affect different species. We reviewed the literature on host genetic factors related to coronaviruses, systematically focusing on human studies. We identified 1,832 articles of potential relevance. Seventy-five involved human host genetic factors, 36 of which involved analysis of specific genes or loci; aside from one meta-analysis, all were candidate-driven studies, typically investigating small numbers of research subjects and loci. Three additional case reports were described. Multiple significant loci were identified, including 16 related to susceptibility (seven of which identified protective alleles) and 16 related to outcomes (three of which identified protective alleles). The types of cases and controls used varied considerably; four studies used traditional replication/validation cohorts. Among other studies, 30 involved both human and non-human host genetic factors related to coronavirus, 178 involved study of non-human (animal) host genetic factors related to coronavirus, and 984 involved study of non-genetic host factors related to coronavirus, including involving immunopathogenesis. Previous human studies have been limited by issues that may be less impactful now, including low numbers of eligible participants and limited availability of advanced genomic methods; however, these may raise additional considerations. We outline key genes and loci from animal and human host genetic studies that may bear investigation in the study of COVID-19. We also discuss how previous studies may direct current lines of inquiry.


Correlation between quality of life and burden of family caregivers of infants with cleft lip and palate.
To evaluate the correlation between measures of quality of life and burden in family caregivers of infants with cleft lip and palate and to analyze possible associations between quality of life and sociodemographic variables. Exploratory, cross-sectional study conducted in hospital specialized in the treatment of craniofacial anomalies, with caregivers who answered the following data collection instruments: sociodemographic characterization form, World Health Organization Quality of Life - BREF questionnaire and the Burden Interview Scale. The statistical analysis was conducted using the Pearson's Correlation test, the Student's t-test and the ANOVA test with a level of significance of 0.05. 77 caregivers participated in the study. There was an inverse correlation between quality of life and burden in the Physical Health, Psychological, Social Relationships and Environment domains. There was a positive correlation between quality of life and family income in the Environment domain. The greater the burden on the caregiver, the lower was their perception of quality of life. Caregivers with higher family income and greater level of education presented a better perception quality of life in the Environment domain.


Evaluation of the NucliSens Basic Kit for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in genital tract specimens using nucleic acid sequence-based amplification of 16S rRNA.
We evaluated a new RNA amplification and detection kit, the NucliSens Basic Kit (Organon Teknika), for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae in genitourinary specimens. The Basic Kit provides an open platform for RNA amplification and detection and contains isolation reagents for nucleic acid extraction, nucleic acid sequence-based amplification (NASBA) reagents (enzymes and buffers), and a generic ruthenium-labeled probe for electrochemiluminescent (ECL) detection of amplified product. Using freshly purified and titrated stocks of C. trachomatis and N. gonorrhoeae and in vitro-generated RNA transcripts for sensitivity determinations, the Basic Kit detected 1 inclusion-forming unit of C. trachomatis, 1 CFU of N. gonorrhoeae, and 100 RNA molecules of 16S rRNA for both bacteria. The clinical performance of the Basic Kit was evaluated by testing a total of 250 specimens for N. gonorrhoeae by culture and NASBA and a total of 96 specimens for C. trachomatis by PCR and NASBA. The Basic Kit detected 139 of 142 N. gonorrhoeae culture-positive specimens and gave a negative result for 73 of 74 culture-negative specimens, for a sensitivity and specificity of 97.9 and 98.7%, respectively. For C. trachomatis, the Basic Kit detected 24 of 24 PCR-positive specimens and gave a negative result for 71 of 72 PCR-negative specimens, for a sensitivity and specificity of 100 and 98.6%, respectively. The Basic Kit also detected specimens containing both N. gonorrhoeae and C. trachomatis, using a multiplex NASBA assay using primers for both bacteria. The NucliSens Basic Kit offers a versatile platform for the development of sensitive RNA detection assays for sexually transmitted diseases.


Design and formulation technique of a novel drug delivery system for azithromycin and its anti-bacterial activity against Staphylococcus aureus.
Azithromycin, an important member of the azalide subclass is effective against both Gram-positive and Gram-negative organisms. Certain physicochemical properties of the drug like poor water solubility and relatively low bioavailability of 37% due to incomplete absorption after ingestion, aroused the need for the development of a novel drug delivery system to enhance the solubilization potential and antibacterial activity against Staphylococcus aureus at a very low concentration. Cinnamon oil (Cinnamonum zeylanicum)-based microemulsion system formulated using non-ionic surfactant, Tween 20, and water was characterized. The drug-incorporated system F4 (oil to surfactant ratio of 1:4 (v/v)) showed enhanced solubilization of the drug, droplet diameter of 5-8 nm, and a good thermodynamic stability. The effect of surfactant concentration exhibited a negative correlation with droplet size diameter and turbidity and a positive correlation with stability and viscosity. The system was investigated for its antibacterial activity that demonstrated a significantly higher activity at a minimum concentration (4 μg/ml) of the novel drug-loaded system in comparison with the conventional formulation (128 μg/ml). Examination through scanning electron microscopy analysis further confirmed a considerable morphologic variation due to alteration in the membrane permeability of the microemulsion-treated system. The small droplet size of the microemulsion system and the antibacterial property of cinnamon oil, together, accounts clearly for the enhanced efficacy of the new formulated system F4 and not just azithromycin alone. Staining with acridine orange/ethidium bromide dyes as examined through fluorescence microscopy also substantiated with the results of membrane permeability of bacteria. Thus, our study discloses a potential oral drug delivery system of azithromycin with improved biocompatibility.


A case of primary bacteraemia caused by Salmonella enterica serovar Corvallis in an immunocompetent adult after travel to Southeast Asia.
Non-typhoidal Salmonella (NTS) that typically causes diarrhoeal disease in humans has a dramatically more severe and more invasive presentation than typhoid fever in immunocompromised adults. However, the incidence and significance of NTS primary bacteraemia in immunocompetent adults have been unclear. A 24-year-old man presented to our hospital with a high fever 14 days after travelling to Vietnam and Cambodia for 14 days. His past medical history, family history and social history were unremarkable, except for his dietary intake history during his stay in Southeast Asia. He did not have any abdominal pain, diarrhoea, enterocolitis, arthritis, or abscesses, as determined by multiple examinations, which included computed tomography. The initial blood cultures identified the presence of Gram-negative bacilli, which were finally identified as the Salmonella enterica subspecies serovar Corvallis. Thus, S. enterica serovar Corvallis was the most likely primary bacteria in this patient. Since domestic outbreaks of NTS infections are extremely rare, our case patient was diagnosed with travel-related bacteraemia. The patient had an uneventful recovery after antibiotic administration. We report a rare case of bacteraemia caused by S. enterica serovar Corvallis in an immunocompetent adult after travelling through Vietnam and Cambodia. From the experience of our case, we suggest that more caution is necessary when diagnosing the unique clinical features of travel-related NTS infections.


Distinct gene expression profiles: nodal versus extranodal diffuse large B-cell lymphoma.
Approximately one third of diffuse large B-cell lymphomas (DLBCL) arises from tissues different from the lymph node. Perceived differences in outcome between extranodal and nodal DLBCL raise the possibility that these subgroups may represent different biological and clinical entities. Microarray GeneChip technology was used for global gene expression profiles from nodal (n = 19) and extranodal (n = 8) DLBCL, to examine possible differences between these subgroups. Quantitative RT-PCR was employed for validation of microarray data. Differential expression levels of p16 (CDKN2A) were confirmed by means of immunohistochemistry on a tissue microarray comprising more than 200 lymphoma samples. A total of 218, over (124)- and underexpressed (94) genes were found to be differentially expressed in extranodal DLBCL compared with nodal DLBCL, including cytokines/chemokines, chromosome-replication-related genes and DNA repair genes. Quantitative RT-PCR confirmed the microarray data. A higher rate of p16 positivity was found in extranodal lymphomas. However, prognostic importance of p16 was associated with nodal rather than extranodal lymphomas. Our data suggest that a better distinction of these subgroups based on molecular classifiers is feasible and may greatly facilitate the determination of specific relevant clinical features and therapeutic implications of DLBCL with primary extranodal or nodal location.


Oxidative stress studies in yeast with a frataxin mutant: a proteomics perspective.
Cellular response of wild-type Saccharomyces cerevisiae and the Delta yfh1 mutant to oxidative stress (OS) was examined by stressing cells through the addition of H(2)O(2) to the growth medium. The Delta yfh1 mutant is unusual in that it accumulates iron in it is mitochondria. Wild-type growth was immediately arrested and recovered in 2 h following H(2)O(2) treatment. No change in viability was observed. Growth of the mutant, on the other hand, was similar to wild-type yeast for 4 h but then rapidly declined, eventually reaching zero. Levels of carbonyl groups and reactive oxygen species (ROS) reached their maximum at 3 h following exposure. The impact of OS on protein function was also evaluated by proteomic techniques targeting protein carbonylation. Oxidized proteins were selected by affinity chromatography, and following trypsin digestion, peptide fragments were identified by RPLC-MS/MS. A total of 53 proteins were identified in both wild-type and mutant cells, respectively.


Issues in women's participation in a phase III community HIV vaccine trial in Thailand.
To assess qualities and outcomes of women participating in a large, community-based HIV vaccine trial, the present study was conducted among female participants of the RV 144 prime-boost trial in Thailand from 2003 to 2009. Qualities of participation refer to complete vaccination, retention, and status change. Outcomes of participation refer to incident rate, adverse event, and participation impact event. A total of 6,334 (38.6%) women participated in the trial, of whom about 50% were classified as low risk and 11% as high risk. About 85% of participants completed four vaccinations and 76% were included in the per-protocol analysis of the on-time vaccination schedule. More women (88%) completed 42 months follow-up compared with men (85%). Women aged 21 and above had more adverse events compared to younger age groups. More women (5%) compared with men (3%) reported participation impact events (PIEs). High-risk women had more PIEs and a higher infection rate compared to the low-risk group. Complete vaccination and retention on last follow-up were more common in married women aged above 21, and being a housewife. Female volunteers showed the same qualities and outcomes of participation as males in the HIV vaccine trial. There was no statistically significant difference in vaccine efficacy between men and women, especially among the high-risk and married women. The study highlighted the important behavioral, social, and cultural issues that could be considered for future HIV vaccine trial designs.


Reliability and validity of the Test of In-Hand Manipulation in children ages 5 to 6 years.
The Test of In-Hand Manipulation (TIHM; Case-Smith, 2000) is a five-task test that uses a 9-hole pegboard to examine 2 key components of in-hand manipulation: rotation and translation with stabilization. The authors used Rasch modeling to examine the TIHM's construct validity, interrater reliability, and test-retest reliability in 45 typically developing children ages 5.5 years to 6.5 years. A version of the test, revised using Rasch modeling, was found to have evidence for adequate construct validity and excellent interrater reliability. However, test-retest reliability over a 2-week retest period was not supported. The TIHM demonstrates potential as a clinically useful assessment of in-hand manipulation. The test does not examine all aspects of in-hand manipulation, however, and it may have limited sensitivity to the performance of finger-to-palm and palm-to-finger translation. Further validation of the test is needed before the TIHM can confidently be used in occupational therapy practice.


The protective effect of ascorbate in retinal light damage of rats.
Cyclic light and dark-reared rats were exposed to intense visible light for various periods and then rhodopsin-measured following recovery in darkness for up to 14 days. Animals were injected with ascorbic acid or ascorbate derivatives at various doses prior to light exposure in green Plexiglas chambers. The results show that ascorbic acid administration elevates retinal ascorbate and reduces the loss of rhodopsin and photoreceptor cell nuclei resulting from intense light. When given in comparable doses, L-ascorbic acid, sodium ascorbate, and dehydroascorbate were equally effective in preserving rhodopsin. The ascorbate protective effect in the retina is also dose dependent in both cyclic light and dark-reared rats and exhibits a requirement for the L-stereoisomer of the vitamin. Ascorbic acid is effective when administered before, but not after, light exposure, suggesting that protection from light damage in the retina occurs during the light period. In some experiments, rod outer segments were isolated from rats immediately after light exposure, lipids extracted, and fatty acid composition determined. As judged by the preservation of rod outer segment docosahexaenoic acid in rats given ascorbate, the vitamin may act in an antioxidative fashion by inhibiting oxidation of membrane lipids during intense light.


Melanesian mtDNA complexity.
Melanesian populations are known for their diversity, but it has been hard to grasp the pattern of the variation or its underlying dynamic. Using 1,223 mitochondrial DNA (mtDNA) sequences from hypervariable regions 1 and 2 (HVR1 and HVR2) from 32 populations, we found the among-group variation is structured by island, island size, and also by language affiliation. The more isolated inland Papuan-speaking groups on the largest islands have the greatest distinctions, while shore dwelling populations are considerably less diverse (at the same time, within-group haplotype diversity is less in the most isolated groups). Persistent differences between shore and inland groups in effective population sizes and marital migration rates probably cause these differences. We also add 16 whole sequences to the Melanesian mtDNA phylogenies. We identify the likely origins of a number of the haplogroups and ancient branches in specific islands, point to some ancient mtDNA connections between Near Oceania and Australia, and show additional Holocene connections between Island Southeast Asia/Taiwan and Island Melanesia with branches of haplogroup E. Coalescence estimates based on synonymous transitions in the coding region suggest an initial settlement and expansion in the region at approximately 30-50,000 years before present (YBP), and a second important expansion from Island Southeast Asia/Taiwan during the interval approximately 3,500-8,000 YBP. However, there are some important variance components in molecular dating that have been overlooked, and the specific nature of ancestral (maternal) Austronesian influence in this region remains unresolved.


Human telomerase reverse transcriptase promoter-driven oncolytic adenovirus with E1B-19 kDa and E1B-55 kDa gene deletions.
We constructed an oncolytic adenovirus, Adeno-hTERT-E1A, with deletions of the viral E1B, E3A, and E3B regions and insertion of a human telomerase reverse transcriptase (hTERT) promoter-driven early viral 1A (E1A) cassette that confers high transcriptional activity in multiple human tumor cell lines. The oncolytic potential of Adeno-hTERT-E1A was characterized in comparison with that of the E1B-55 kDa- and E3B-region-deleted oncolytic adenovirus ONYX-015. Tumor cells infected with Adeno-hTERT-E1A expressed dramatically higher levels of E1A oncoprotein, underwent enhanced lysis, and displayed an earlier and higher apoptotic index than cells infected with ONYX-015. Despite the increase in virus-induced apoptotic death, Adeno-hTERT-E1A replicated and produced functional progeny leading to viral spread, but with reduced efficiency compared with ONYX-015, in particular in A549 cells. Virus-induced E1A expression, host cell apoptosis, viral hexon protein production, and DNA synthesis were markedly reduced in primary human hepatocytes after infection with Adeno-hTERT-E1A as compared with ONYX-015. The strong oncolytic activity of Adeno-hTERT-E1A in tumor cell culture translated into superior antitumor activity in vivo in an MDA-MB-231 solid tumor xenograft model. Adeno-hTERT-E1A thus has strong therapeutic potential and an improved safety profile compared with ONYX-015, which may lead to reduced toxicity in the clinic.


IL-13 induces phosphorylation and activation of JAK2 Janus kinase in human colon carcinoma cell lines: similarities between IL-4 and IL-13 signaling.
We have recently reported that IL-13R may share a component with IL-4R. Here we report that both IL-4 and IL-13 share signaling events in human colon carcinoma cell lines (HT-29 and WiDr). IL-13 caused rapid phosphorylation of the three out of four members of the known Janus family of kinases (JAKs). We show that JAK2 kinase is rapidly phosphorylated and activated in response to IL-13. Within 1 min of activation, JAK2 was phosphorylated, and peaked in 10 min. In addition, IL-13 phosphorylated insulin response substrate-1, IL-4R p140, JAK1, and Tyk2, but not JAK3 kinase. IL-4 also stimulated all three kinases and substrates, but unlike in immune cells, IL-4 did not involve JAK3 activation for its signaling in colon cancer cell lines. Furthermore, JAK2 associated with the IL-4R p140 before and after stimulation with IL-13. Both IL-13 and IL-4 induced phosphorylation of IL-4 STAT (STAT6) but not STAT1, STAT3, or STAT5. 125I-IL-13 did not bind to colon cancer cell lines, but unlabeled IL-13 competed for the binding of 125I-IL-4. Our data suggest that IL-13 utilizes IL-4R and its signaling pathway, and JAK2 may play an important role in the function of IL-4R and IL-13R in colon cancer cells.


Differential expression of Ia antigens by rheumatoid synovial lining cells.
The differential expression of Ia antigens was studied in freshly isolated rheumatoid nonlymphoid synovial lining cells (SLC) and rheumatoid synovial fibroblast cell lines cultured in the presence of Interferon-gamma, using a large panel of anti-Ia reagents with monomorphic or polymorphic specificities. All the HLA-DR or -DQ specificities detectable on the corresponding peripheral blood B cells were also expressed in freshly isolated SLC. However, in all instances, the number of DR-positive SLC exceeded the percentage of cells expressing DQ antigens. In addition, the epitope expression of Ia antigens varied within the DR or DQ populations of Ia molecules as revealed by polymorphic reagents. Double-label experiments or using the ingestion of Latex particles as a marker demonstrated that the synovial macrophages (type I SLC) primarily bear the DR+DQ+ phenotype, while there is an additional population of nonphagocytic SLC (previously termed type II SLC) that has a DR+ and monocyte marker negative phenotype but did not have detectable levels of DQ antigens as analyzed by both fluorescence microscopy and cell sorter analysis. This latter population frequently had a morphology showing dendritic processes and rapidly lost the expression of Ia antigens upon culture. Cells with a similar, primarily DR+ phenotype were readily obtained in synovial fibroblast cultures after treatment with Interferon-gamma. These data suggest that there are two populations of Ia+ synovial lining cells: the synovial macrophages (type I cells) with the DR+DQ+ phenotype, and cells probably related to fibroblasts with a DR+ phenotype without detectable DQ antigens (type II cells). The fact that the latter phenotype could be induced by Interferon-gamma treatment of cultured synovial fibroblasts suggests that this mediator may have a similar role in vivo in the activation of certain synovial cell populations.


Participation in a population-based physical activity programme as an aid for smoking cessation: a randomised trial.
Exercise combined with nicotine therapy may help smoking cessation and minimise weight gain after quitting. Low participation in vigorous-intensity physical activity programmes precludes their population-wide applicability. In a randomised controlled trial, we tested whether a population-based moderate-intensity physical activity programme increases quit rates among sedentary smokers receiving nicotine therapy. Participants (n=481; 57% male; mean age, 42.2 years (SD 10.1); mean cigarette consumption, 27 (SD 10.2) per day) were offered a nine-week smoking cessation programme consisting of a weekly 15-minute counselling session and the prescription of nicotine replacement therapy. In addition, participants in the physical activity group (n=229) also took part in a programme of moderate-intensity physical activity implemented at the national level, and offering nine weekly 60-minute sessions of physical activity. To ensure equal contact conditions, participants in the control group (n=252) attended weekly 60-minute health behaviour education sessions unrelated to physical activity. The primary outcome was continuous CO-verified smoking abstinence rates at 1-year follow-up. Continuous smoking abstinence rates were high and similar in the physical activity group and the control group at the end of the intervention (47% versus 46%, p=0.81) and at 1-year follow-up (27% versus 29%, p=0.71). The mean weight gain after one year was 4.4 kg and 6.2 kg among sustained quitters of the physical activity and control groups, respectively (p=0.06). Participation in a population-based moderate-intensity physical activity programme for 9 weeks in addition to a comprehensive smoking cessation programme did not significantly increase smoking cessation rates. A non-significant reduction in weight gain was observed among participants who quit smoking in the physical activity group. ClinicalTrials.gov; US National Institutes for Health (available online at http://clinicaltrials.gov/; NCT00521391).


Infectious disease and risk of later celiac disease in childhood.
The goal was to examine whether parent-reported infection at the time of gluten introduction increases the risk of future celiac disease (CD). Through the population-based All Infants in Southeast Sweden study, parents recorded data on feeding and infectious disease prospectively. Complete data on gluten introduction and breastfeeding duration were available for 9408 children. Those children had 42 826 parent-reported episodes of infectious disease in the first year of life (including 4003 episodes of gastroenteritis). We identified 44 children with biopsy-verified CD diagnosed after 1 year of age, and we used Cox regression to estimate the risk of future CD for children with infection at gluten introduction. Eighteen children with CD (40.9%) had an infection at the time of gluten introduction, compared with 2510 reference individuals (26.8%; P = .035). Few children had gastroenteritis at the time of gluten introduction (1 child with CD [2.3%] vs 166 reference individuals [1.8%]; P = .546). With adjustment for age at gluten introduction and breastfeeding duration, we found no association between a future diagnosis of CD and either any infection (adjusted hazard ratio: 1.8 [95% confidence interval: 0.9-3.6]) or gastroenteritis (adjusted hazard ratio: 2.6 [95% confidence interval: 0.2-30.8]) at the time of gluten introduction. We found no associations between breastfeeding duration, age at gluten introduction, and future CD. These results indicate that parent-reported infection at the time of gluten introduction is not a major risk factor for CD.


Hamartomas and midline anomalies in association with infantile hemangiomas, PHACE, and LUMBAR syndromes.
The pathogenesis of infantile hemangiomas (IH), PHACE, and LUMBAR syndromes remains unknown. We aim to describe histopathologic features of midline anomalies associated with IH, including patients with PHACE and LUMBAR syndromes. A multicenter retrospective chart review was performed to identify patients with IH, PHACE, and LUMBAR syndrome with histopathologic specimens from sternal or midline anomalies. A total of 18 midline lesions from 13 patients were included. Out of 18, 14 midline lesions underwent both histopathologic and clinical review. Three hamartoma-like chin plaques and one supraumbilical raphe underwent only clinical review. All 13 patients had midline lesions and IH. Histopathologic diagnoses were as follows: rhabdomyomatous mesenchymal hamartoma (3), folliculosebaceous cystic hamartoma (1), fibroepithelial polyp (1), verrucous epidermal hyperplasia with vascular proliferation and fibroplasia (1), congenital midline cervical cleft (1), pericardium with fibrosis (1), fibrous components with increased collagen (1), atrophic skin/membrane (3), angiolipomatous mass with neural components (1), and lipomatous mass (1). Due to the retrospective nature of this study, it was not possible to obtain pathology slides for all midline lesions that had previously been biopsied or resected. We show clinically and histopathologically a new association between PHACE syndrome and rhabdomyomatous mesenchymal hamartoma (RMH), in addition to demonstrating the association between PHACE syndrome and chin hamartomas. We also display histopathologic findings seen in midline lesions resected from LUMBAR patients. Rhabdomyomatous mesenchymal hamartoma is thought to be related to aberrations of mesenchymal cells during development; therefore, this may provide clues to the pathogenesis of IH and related syndromes.


Nucleoside hydrolase from Crithidia fasciculata. Metabolic role, purification, specificity, and kinetic mechanism.
Crithidia fasciculata cells grown on complex medium with added [8-14C, 5'-3H]inosine or [8-14C,5'-3H]adenosine metabolize greater than 50% of the salvaged nucleosides through a pathway involving N-glycoside bond cleavage. Cell extracts contain a substantial nucleoside hydrolase activity but an insignificant purine nucleoside phosphorylase. The nucleoside hydrolase has been purified 1000-fold to greater than 99% homogeneity from kilogram quantities of C. fasciculata. The enzyme is a tetramer of Mr 34,000 subunits to give an apparent holoenzyme Mr of 143,000 by gel filtration. All of the commonly occurring nucleosides are substrates. The Km values vary from 0.38 to 4.7 mM with purine nucleosides binding more tightly than the pyrimidines. Values of Vmax/Km vary from 3.4 x 10(3) M-1 s-1 to 1.7 x 10(5) M-1 s-1 with the pyrimidine nucleosides giving the larger values. The turnover rate for inosine is 32 s-1 at 30 degrees C. The kinetic mechanism with inosine as substrate is rapid equilibrium with random product release. The hydrolytic reaction can be reversed to give an experimental Keq of 106 M with H2O taken as unity. The product dissociation constants for ribose and hypoxanthine are 0.7 and 6.2 mM, respectively. Deoxynucleosides or 5'-substituted nucleosides are poor substrates or do not react, and are poor inhibitors of the enzyme. The enzyme discriminates against methanol attack from solvent during steady-state catalysis, indicating the participation of an enzyme-directed water nucleophile. The pH profile for inosine hydrolysis gives two apparent pKa values of 6.1 with decreasing Vmax/Km values below the pKa and a plateau at higher pH values. These effects are due to the pH sensitivity of the Vmax values, since Km is independent of pH. The pH profile implicates two negatively charged groups which stabilize a transition state with oxycarbonium character.


Periventricular changes associated with spontaneous canine hydrocephalus.
Causes of canine juvenile hydrocephalus have been well documented. However, the effects of hydrocephalus on periventricular white matter have been only partially described. The present report shows that hydrocephalus-associated lesions of the periventricular white matter, i.e., formation of diverticula, clefts, and tears, are prevalent. Marked hydrocephalus was identified at necropsy in 20 juvenile dogs between 1990 and 1999. The severity grade was based upon a ratio of lateral ventricular dimensions to cortical thickness. All animals exhibited ependymal lesions consisting of attenuation, with or without abortive attempts of ependymal regeneration, and ulceration. In 10 dogs (50%), unilateral or bilateral periventricular diverticula and cleft formation in the region of the caudate nucleus were observed. The diverticula were formed at the caudal pole of the caudate nucleus, communicated with the ventricular lumen, and were associated with ependymal denudation. Loss of the ependymal lining probably contributes to a bulk shift of cerebrospinal fluid from the ventricular lumen to the periventricular white matter, leading to diverticulum formation. Clefts were observed within the parenchyma at the border of the internal capsule and putamen, consistent with an ischemic insult. Occasionally tearing with separation of the caudate nucleus from the subcortical white matter was found, representing unification of expanding clefts and diverticula. In one of the few clinically well-documented cases, tearing was correlated with a sudden decline in neurologic function, culminating in euthanasia. However, tears and clefts may exhibit a chronicity of several days, as indicated by the presence of astroglial scars along the lesion margins.


Increasing sampling density improves reproducibility of optical coherence tomography measurements.
Published series of peripapillary retinal nerve fiber layer (RNFL) measurements using optical coherence tomography (OCT) have sampled 100 evenly distributed points on a 360 degrees peripapillary circular scan. The goal of this study was to determine whether a four-fold increase in sampling density improves the reproducibility of OCT measurements. Complete ophthalmic examinations, achromatic automated perimetry, and OCT imaging were performed in all patients. The OCT scanning consisted of three superior and inferior quadrantic scans (100 sampling points/quadrant) and three circular scans (25 points/quadrant). The RNFL thickness measurements and coefficient of variation (CV) were calculated for the superior and inferior quadrants for each sampling density technique. The study included 22 eyes of 22 patients (3 control subjects; 2 patients with ocular hypertension; and 17 patients with glaucoma). Quadrants with associated glaucomatous visual field loss on automated achromatic perimetry had thinner RNFLs than quadrants without functional defects for both the 25- and 100-points/quadrant scans. For quadrants associated with normal visual hemifields (n = 22), there was no difference between the 25- and 100-points/quadrant scans in mean RNFL thickness and CV. Among quadrants with visual field defects (n = 22), RNFL thickness measurements were thinner in the 25-points/quadrant scans than in the 100-points/quadrant scans. The CV for the 25-points/quadrant scans (25.9%) was significantly higher than that for the 100-points/quadrant scans (11.9%). Increasing the sampling density of OCT scans provides less variable representation of RNFL thickness. The optimal sampling density to achieve maximal reliability of OCT scans remains to be determined.


Management of acute grief.
Family physicians must often help patients through the grief process. Acute grief may occur with the loss of a loved one or with the loss of physical health. Normal grief has well-defined stages, which help distinguish it from pathologic grief reactions. Familiarity with the grief process allows the physician to intervene when necessary and to facilitate the normal sequence of grieving which, if thwarted, has serious ramifications.


The effect of volunteers' care and support on the health outcomes of older adults in acute care: A systematic scoping review.
To examine the available evidence on the effects of care and support provided by volunteers on the health outcomes of older adults in acute care services. Acute hospital inpatient populations are becoming older, and this presents the potential for poorer health outcomes. Factors such as chronic health conditions, polypharmacy and cognitive and functional decline are associated with increased risk of health care-related harm, such as falls, delirium and poor nutrition. To minimise the risk of health care-related harm, volunteer programmes to support patient care have been established in many hospitals worldwide. A systematic scoping review. The review followed the PRISMA Extension for Scoping Reviews (PRISMA-ScR) (File S1). Nine databases were searched (CINAHL, MEDLINE, EMBASE, Cochrane, Scopus, Web of Science, PubMed, ScienceDirect and JBI) using the following key terms: 'hospital', 'volunteer', 'sitter', 'acute care', 'older adults', 'confusion', 'dementia' and 'frail'. The search was limited to papers written in English and published from 2002-2017. Inclusion criteria were studies involving the use of hospital volunteers in the care or support of older adult patients aged ≥ 65 years, or ≥ 50 years for Indigenous peoples, with chronic health conditions, cognitive impairment and/or physical decline or frailty, within the acute inpatient settings. Of the 199 articles identified, 17 articles that met the inclusion criteria were critically appraised for quality, and 12 articles were included in the final review. There is evidence that the provision of volunteer care and support with eating and drinking, mobilising and therapeutic activities can impact positively upon patient health outcomes related to nutrition, falls and delirium. Further robust research is needed to determine the impact of volunteers in acute care and the specific care activities that can contribute to the best outcomes for older adults. Volunteers can play a valuable role in supporting care delivery by nurses and other health professionals in acute care services, and their contribution can improve health outcomes for older adults in this setting.


Diarrhetic Shellfish Toxin Monitoring in Commercial Wild Harvest Bivalve Shellfish in New South Wales, Australia.
An end-product market survey on biotoxins in commercial wild harvest shellfish (Plebidonax deltoides, Katelysia spp., Anadara granosa, Notocallista kingii) during three harvest seasons (2015⁻2017) from the coast of New South Wales, Australia found 99.38% of samples were within regulatory limits. Diarrhetic shellfish toxins (DSTs) were present in 34.27% of 321 samples but only in pipis (P. deltoides), with two samples above the regulatory limit. Comparison of these market survey data to samples (phytoplankton in water and biotoxins in shellfish tissue) collected during the same period at wild harvest beaches demonstrated that, while elevated concentrations of Dinophysis were detected, a lag in detecting bloom events on two occasions meant that wild harvest shellfish with DSTs above the regulatory limit entered the marketplace. Concurrently, data (phytoplankton and biotoxin) from Sydney rock oyster (Saccostrea glomerata) harvest areas in estuaries adjacent to wild harvest beaches impacted by DSTs frequently showed elevated Dinophysis concentrations, but DSTs were not detected in oyster samples. These results highlighted a need for distinct management strategies for different shellfish species, particularly during Dinophysis bloom events. DSTs above the regulatory limit in pipis sampled from the marketplace suggested there is merit in looking at options to strengthen the current wild harvest biotoxin management strategies.


The frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude.
With the advent of MRI scanning, the value of lumbar puncture to assess oligoclonal band (OCB) status-for the diagnosis of multiple sclerosis (MS) is increasingly uncertain. One major issue is that the reported frequency of cerebrospinal fluid (CSF)-restricted oligoclonal banding for the diagnosis of MS varies considerably in different studies. In addition, the relationship between OCB positivity and disease outcome remains uncertain, as reported studies are generally too small to assess comparative disability outcomes with sufficient power. In order to further investigate variation of OCB positivity in patients with MS, we utilized MSBase, a longitudinal, Web-based collaborative MS outcomes registry following clinical cohorts in several continents and latitudes. We also assessed whether OCB positivity affects long-term disability outcome. A total of 13,242 patient records were obtained from 37 MS specialist centres in 19 different countries. OCB status was documented in 4481 (34%) patients and 80% of these were OCB positive. The presence of OCB was associated with degree of latitude (p = 0.02). Furthermore, the outcome of patients negative for CSF-specific OCB was significantly better in comparison to the OCB positive patients, as assessed by Expanded Disability Status Scale change (p < 0.001). The results of this study indicate that latitude could explain some of the inconsistencies in OCB status reported in different populations. The study confirms that OCB positivity in MS is associated with a worse long-term prognosis.


Semiquantitative Imaging Biomarkers of Knee Osteoarthritis Progression: Data From the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium.
To determine the association between changes in semiquantitative magnetic resonance imaging (MRI) biomarkers over 24 months and radiographic and pain progression over 48 months in knees with mild-to-moderate osteoarthritis (OA). We undertook a nested case-control study as part of the Foundation for the National Institutes of Health Biomarkers Consortium Project. We used multivariable logistic regression models to examine the association between change over 24 months in semiquantitative MRI markers and radiographic and pain progression in knee OA. MRIs were read according to the MRI OA Knee Score system. We focused on changes in cartilage, osteophytes, meniscus, bone marrow lesions, Hoffa-synovitis, and effusion-synovitis. The most parsimonious model included changes in cartilage thickness and surface area, effusion-synovitis, Hoffa-synovitis, and meniscal morphology (C statistic 0.740). Compared with no worsening, worsening in cartilage thickness in ≥3 subregions was associated with 2.8-fold (95% confidence interval [95% CI] 1.3-5.9) greater odds of being a case, and worsening in cartilage surface area in ≥3 subregions was associated with 2.4-fold (95% CI 1.3-4.4) greater odds of being a case. Worsening of meniscal morphology in any region was associated with 2.2-fold (95% CI 1.3-3.8) greater odds of being a case. Worsening effusion-synovitis and Hoffa-synovitis were also associated with a greater odds of being a case (odds ratios 2.7 and 2.0, respectively). Twenty-four-month changes in cartilage thickness, cartilage surface area, effusion-synovitis, Hoffa-synovitis, and meniscal morphology were independently associated with OA progression, suggesting that these factors may serve as efficacy biomarkers in clinical trials of disease-modifying interventions for knee OA.


Fenofibrate increases homocystinemia through a PPARalpha-mediated mechanism.
Plasma homocysteine levels increase in humans treated with fibrates but the molecular mechanisms are unknown. The goal of the present study was to determine the mechanism of this increase using animal models. Firstly, an increase in homocysteine was observed in mice treated with fenofibrate irrespective of the genetic background C57BL/6 or SV129. Secondly, as the effect of fenofibrate on gene expression is mediated through activation of the peroxisome proliferator-activated receptor alpha (PPARalpha), a transcription factor belonging to the nuclear receptor family, it was determined whether the effect of fenofibrate on homocysteine levels were modulated through PPARalpha activation. Using PPARalpha-deficient mice, it was shown that the homocysteine increase after fenofibrate treatment was completely abolished in these animals. It can be concluded that fibrates increase homocystinemia through a PPARalpha-mediated mechanism and that mice constitute an animal model for analyzing the molecular mechanisms behind the homocysteine increase after fibrate therapy in dyslipidemic patients.


Comparing DNA isolation methods for forest trees: quality, plastic footprint, and time-efficiency.
Genetic and genomic studies are seeing an increase in sample sizes together with a wider range of species investigated in response to environmental change concerns. In turn, these changes may come with challenges including the time and difficulty to isolate nucleic acids (DNA or RNA), the sequencing cost and environmental impacts of the growing amount of plastic waste generated in the process. Pseudotsuga menziesii var. menziesii (Mirbel) Franco (PM), Tsuga heterophylla (Raf.) Sarg. (TH) and Thuja plicata Donn ex D.Don (TP) are conifer species found in diverse woodlands both as natives and naturalized exotics. Our study was carried out whilst investigating their genetics to understand their population structure and potential for adaptation. In the present study, we compared two different DNA isolation methods, i.e., spin-column DNeasy plant mini kit (QIAGEN), and temperature-driven enzymatic cocktail Plant DNA Extraction (MicroGEM). The quantity of recovered DNA and the quality of DNA were assessed along with the plastic footprint and time needed for three tree species. Both methods were optimised and proven to provide enough DNA for each studied species. The yield of DNA for each method depended on the species: QIAGEN showed higher yield in P. menziesii and T. heterophylla, while T. plicata recovered similar amount of DNA for both methods. The DNA quality was investigated using DNA barcoding techniques by confirming species identity and species discrimination. No difference was detected in the PCR amplification of the two barcoding loci, (rbcL and trnH-psbA), and the recovered sequences between DNA isolation methods. Measurement of the plastic use and the processing time per sample indicated that MicroGEM had a 52.64% lower plastic footprint and was 51.8% faster than QIAGEN. QIAGEN gave higher yields in two of the species although both methods showed similar quality results across all species. However, MicroGEM was clearly advantageous to decrease the plastic footprint and improve the time efficiency. Overall, MicroGEM recovers sufficient and reliable DNA to perform common downstream analyses such as PCR and sequencing. Our findings illustrate the benefits of research and efforts towards developing more sustainable methods and techniques to reduce the environmental footprint of molecular analyses.


Immunological relationships between hexons of certain human adenoviruses.
Antisera against hexons of serotypes 2, 4, 5, and 6 (subgroup III), and 15 (subgroup II) were absorbed with purified hexons of various serotypes representing the different subgroups of human adenoviruses. Group, subgroup, and type specificities of hexons could be distinguished. The subgroup specificity of type 4 hexons resembled that of hexons of subgroup I members (types 3, 11, and 16). Antihexon sera gave a type-specific inhibition of virion-associated hemagglutinin. The inhibiting activity of different sera was found to be inversely related to the length of fibers of the serotype concerned. Virions of serotypes carrying fibers shorter than about 20 nm (types 3, 4, 9, 11, and 15) were readily inhibited, whereas those of serotypes with longer fibers (types 2 and 6) were inhibited only by relatively large amounts of antibody measured in terms of homotypic complement fixation activity. The reciprocal cross-neutralization between serotypes 4 and 16 was studied separately. Hexons of both serotypes each carried a type-specific component and, in addition, a unique antigen specificity common to the two types. This common antigen specificity was interpreted to be available to a larger extent at the surface of virions (and probably also isolated hexons) of type 4 than of type 16. These results suggest an explanation for the predominantly one-sided character of the cross-neutralization between types 4 and 16.


Terpene and dextran renewable resources for the synthesis of amphiphilic biopolymers.
The present work shows the synthesis of amphiphilic polymers based on the hydrophilic dextran and the hydrophobic terpenes as renewable resources. The first step concerns the synthesis of functional terpene molecules by thiol-ene addition chemistry involving amino or carboxylic acid thiols and dihydromyrcenol terpene. The terpene-modified polysaccharides were subsequently synthesized by coupling the functional terpenes with dextran. A reductive amination step produced terpene end-modified dextran with 94% of functionalization, while the esterification step produced three terpene-grafted dextrans with a number of terpene units per dextran of 1, 5, and 10. The amphiphilic renewable grafted polymers were tested as emulsifiers for the stabilization of liquid miniemulsion of terpene droplets dispersed in an aqueous phase. The average hydrodynamic diameter of the stable droplets was observed at about 330 nm.


Effects of dietary antioxidant supplementation before and after oral acetaminophen challenge in cats.
To determine effects of lipoic acid, vitamin E, and cysteine before and after oxidant challenge in cats. 24 sexually intact adult cats. Cats were allocated into 4 equal groups. For 25 weeks, group A was fed a control dry diet and groups B, C, and D received this diet supplemented with vitamin E (2200 U/kg [dry matter basis {DMB}]) plus cysteine (9.5 g/kg [DMB]), lipoate (150 mg/kg [DMB]), or all 3 antioxidants together, respectively. Weights were measured every 3 days and venous blood obtained every 5 weeks for CBC; serum biochemical analyses; lymphocyte blastogenesis; thiobarbituric acid reactive substances concentration; and concentrations of plasma protein carbonyl, 8-OH d-guanosine, blood glutathione, plasma amino acid, lipoate, and dihydrolipoate. At 15 weeks, all cats received acetaminophen (9 mg/kg, PO, once), clinical effects were observed, and methemoglobin concentrations were measured. Lymphocyte blastogenesis increased transiently in group C and D cats. After acetaminophen administration, all groups had transient increases in methemoglobin within 4 hours and mild, brief facial edema; group C had decreased glutathione concentration and increased 8-OH d-guanosine concentration versus controls; and protein carbonyl concentration increased least for group B. Plasma lipoate and dihydrolipoate concentrations peaked by week 10 for groups C and D. Conclusions and Clinical Relevance-Lipoate, vitamin E, and cysteine did not have synergistic effects. Lipoate supplementation (150 mg/kg [DMB]) did not act as an antioxidant but appeared to enhance oxidant effects of acetaminophen. Vitamin E plus cysteine had protective effects.


The Tromsøo heart study. Methods and main results of the cross-sectional study.
The mortality from coronary heart disease (CHD) in Norway increased rapidly during 1951-70, the highest mortality rates as well as the most rapid increases being found in Northern Norway. Several surveys of CHD were then planned, one of them is reported here. All men, 20-49 years of age, living in the municipality of Tromsøo, Troms county, were called up for examination. In total, 6595 men, 74.4% of those invited, were examined. Cholesterol, triglyceride and Hb values, BP, body weight and height, the percentage of smokers, and cigarette consumption have been tabulated according to area, age, work schedule, health condition, physical activity and ethnic background. The results suggest that the relatively high mortality from CHD in Northern Norway is associated with high serum cholesterol concentrations as well as a relatively high prevalence of smoking. During the screening there were indications of changes in dietary habits in the municipality, presumably as a result of accompanying publicity.


An unusual foreign body impaction in the pharynx of a child - a case report and literature review.
Foreign body impaction in the upper aero-digestive tract is relatively common in Otorhino/aryngological practice. The aim is to present a case of an unusual impacted foreign body (ear ring), in the pharynx of a child,that was confirmed by plain radiographs. An 8-month old male baby presented in emergency paediatric unit(EPU) of our hospital with a history of ingestion of an empty paracetamol satchel. Plain X-ray soft tissue of the neck however revealed a big metallic ear ring that impacted in the upper aerodigestive tract. It was removed successfully under general anaesthesia. The possible delay in diagnosis and various complications of pharyngeal foreign bodies were highlighted /reviewed. In conclusion foreign body impaction is common in the paediatric age group. Effort should be made by the attending physician to inquire into details of event relating to ingestion of foreign body in order to arrive at early and timely diagnosis and treatment so as to prevent complications.


Microbiota-Orientated Treatments for Major Depression and Schizophrenia.
There is a need to develop new hypothesis-driven treatment for both both major depression (MD) and schizophrenia in which the risk of depression is 5 times higher than the general population. Major depression has been also associated with poor illness outcomes including pain, metabolic disturbances, and less adherence. Conventional antidepressants are partly effective, and 44% of the subjects remain unremitted under treatment. Improving MD treatment efficacy is thus needed to improve the SZ prognosis. Microbiota-orientated treatments are currently one of the most promising tracks. This work is a systematic review synthetizing data of arguments to develop microbiota-orientated treatments (including fecal microbiota transplantation (FMT)) in major depression and schizophrenia. The effectiveness of probiotic administration in MD constitutes a strong evidence for developing microbiota-orientated treatments. Probiotics have yielded medium-to-large significant effects on depressive symptoms, but it is still unclear if the effect is maintained following probiotic discontinuation. Several factors may limit MD improvement when using probiotics, including the small number of bacterial strains administered in probiotic complementary agents, as well as the presence of a disturbed gut microbiota that probably limits the probiotics' impact. FMT is a safe technique enabling to improve microbiota in several gut disorders. The benefit/risk ratio of FMT has been discussed and has been recently improved by capsule administration. Cleaning up the gut microbiota by transplanting a totally new human gut microbiota in one shot, which is referred to as FMT, is likely to strongly improve the efficacy of microbiota-orientated treatments in MD and schizophrenia and maintain the effect over time. This hypothesis should be tested in future clinical trials.


[Choledochal cyst: a 10-year experience]
BACKGROUND: Choledochal cyst is a rare abnormality usually found in infancy and childhood and mainly in females. Outcome depends on early diagnosis, complete resection of the cyst and proper hepaticoenterostomy.OBJECTIVE: The aim of this paper is to evaluate the outcome of 18 patients operated in ten years. METHODS: Retrospective chart review. RESULTS AND DISCUSSION: Age ranged between 20 days and 13 years (mean 3 years). Fifteen (83%) were female and 03 (17%) male. Signs presented included 15 (83%) with jaundice, 11 (61%) with dark urine, 10(55%) with pale colored stools, 09 (50%) with abdominal pain and palpable mass in only 02(11%). Ultrasonography identified the cyst in 14 (77%) patients. Endoscopic retrograde cholangio-pancreatography demonstrated a long common duct in three of four cases. Anatomical types were: 09 type I, 01 type II, 07 type IV and 01 type V. Except for one patient who had a type V cyst, all patients underwent cyst resection plus Roux-en-Y hepaticojejunostomy. There were two (11%) early postoperative deaths related to deterioration of liver function. Thirteen (86%) of the 15 patients available to follow-up were symptom-free without late complications at a mean period of three years, and two (14%) patients developed chronic pancreatitis.


Respiratory function of children in homes insulated with urea formaldehyde foam insulation.
A study was carried out to assess the respiratory function of children living in homes insulated with urea formaldehyde foam insulation (UFFI). A large data base on the effect of environmental variables on the respiratory function of 3500 children in the Hamilton, Ont., area had been collected from 1978 to 1980. From this data base 29 children who lived in UFFI-insulated homes were identified, and each was matched with 2 controls according to nine variables that had been shown to be strongly predictive of respiratory function. Reported respiratory symptoms and results of pulmonary function testing in the year immediately following installation of UFFI were examined. No significant differences in any variable were found between the subjects and controls. A power calculation indicated that the study had adequate power to detect clinically important changes. The authors conclude that there was no evidence of respiratory problems resulting from UFFI in the sample studied.


SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland.
Population-level data on COVID-19 vaccine uptake in pregnancy and SARS-CoV-2 infection outcomes are lacking. We describe COVID-19 vaccine uptake and SARS-CoV-2 infection in pregnant women in Scotland, using whole-population data from a national, prospective cohort. Between the start of a COVID-19 vaccine program in Scotland, on 8 December 2020 and 31 October 2021, 25,917 COVID-19 vaccinations were given to 18,457 pregnant women. Vaccine coverage was substantially lower in pregnant women than in the general female population of 18-44 years; 32.3% of women giving birth in October 2021 had two doses of vaccine compared to 77.4% in all women. The extended perinatal mortality rate for women who gave birth within 28 d of a COVID-19 diagnosis was 22.6 per 1,000 births (95% CI 12.9-38.5; pandemic background rate 5.6 per 1,000 births; 452 out of 80,456; 95% CI 5.1-6.2). Overall, 77.4% (3,833 out of 4,950; 95% CI 76.2-78.6) of SARS-CoV-2 infections, 90.9% (748 out of 823; 95% CI 88.7-92.7) of SARS-CoV-2 associated with hospital admission and 98% (102 out of 104; 95% CI 92.5-99.7) of SARS-CoV-2 associated with critical care admission, as well as all baby deaths, occurred in pregnant women who were unvaccinated at the time of COVID-19 diagnosis. Addressing low vaccine uptake rates in pregnant women is imperative to protect the health of women and babies in the ongoing pandemic.


Asthma guidelines: the Global Initiative for Asthma in relation to national guidelines.
To compare and contrast national asthma guidelines with the Global Initiative for Asthma (GINA) strategy for asthma management and prevention. The common goal of GINA and national asthma guidelines is to improve asthma care using the best evidence available from published data. This evidence-based approach has evolved from an initial perspective of expert opinion but with that evolution has not always considered the breadth of asthma phenotypes. GINA and national guidelines differ in a number of ways. GINA reviews available data and updates the core document and recommendations based on the latest data on a yearly basis to offer local, regional and national guidelines materials needed for knowledge mobilization. It remains the purview of those organizations to structure and implement those locally appropriate guidelines. Both GINA and national guidelines have furthered asthma care to narrow the care gap from what is known to how asthma care is delivered, hopefully in a more directed, personalized manner. As well, both GINA and national guidelines have helped to shape the direction of research for the future benefit of children and their families.


A Cross Sectional Study of ChatGPT in Translation: Magnitude of Use, Attitudes, and Uncertainties.
This preliminary cross-sectional study, focusing on Artificial Intelligence (AI), aimed to assess the impact of ChatGPT on translation within an Arab context. It primarily explored the attitudes of a sample of translation teachers and students through semi-structured interviews and projective techniques. Data collection included gathering information about the advantages and challenges that ChatGPT, in comparison to Google Translate, had introduced to the field of translation and translation teaching. The results indicated that nearly all the participants were satisfied with ChatGPT. The results also revealed that most students preferred ChatGPT over Google Translate, while most teachers favored Google Translate. The study also found that the participants recognized both positive and negative aspects of using ChatGPT in translation. Findings also indicated that ChatGPT, as a recent AI-based translation-related technology, is more valuable for mechanical processes of writing and editing translated texts than for tasks requiring judgment, such as fine-tuning and double-checking. While it offers various advantages, AI also presents new challenges that educators and stakeholders need to address accordingly.