[Recent transmission of tuberculosis in an area with low incidence: epidemiological and molecular study].
Few reports have analysed the transmission of tuberculosis in rural areas with a low incidence of disease. A population-based molecular epidemiological study of patients with tuberculosis, diagnosed by culture, was conducted in Segovia (Spain) between 1995 and 1999. Clinical, demographic and epidemiological data were reviewed. Patients whose clinical isolates of Mycobacterium tuberculosis had identical restriction-fragment-length-polymorphism (RFLP) patterns with IS6110 and spoligotyping were included in clusters. Of 96 patients with positive-culture for M. tuberculosis complex, 6 were considered as false-positive results. The mean incidence rate was 12.3 cases/100,000 inhabitants. Median age was 50.3 (SD: 23.1), 14% was HIV-infected, and 92% of them were living in urban areas (p < 0.01). There were no cases of primary resistance to isoniazid. DNA fingerprint was performed in 87 samples. We identified 8 clusters including 24 patients (27.7%). Clusters had between 2 and 6 cases. Patients aged < 35 years (OR = 3.1; CI 95%, 1.0-9.6) and with lung involvement (OR = 6.8; CI 95%, 1.3-46.4) were more represented in the clusters. Classical epidemiological investigation confirmed a recent transmission in 33% of clustered cases. The use of both classical and molecular epidemiology reveals the existence of recent transmission cases of tuberculosis in an area with a low incidence of the disease.


Monitoring thymidine kinase and ganciclovir-induced changes in rat malignant glioma in vivo by nuclear magnetic resonance imaging.
We have used high resolution magnetic resonance imaging to monitor malignant rat BT4C gliomas in vivo following herpes simplex virus thymidine kinase gene and ganciclovir (GCV) treatment. Twenty-six female BDIX rats were used for the study including four controls. Serial magnetic resonance imaging was performed every 72 hours to quantify tumor volume, transverse relaxation time (T2) ,and apparent diffusion constant (ADC) of water in the tumors and in the contralateral brain. GCV treatment was given twice a day, intraperitoneally, for 21 days. The gliomas exhibited low T2 and ADC values (before treatment), compared to normal brain, indicating the presence of high cell density tumors. Following GCV treatment, a regional increase in T2 and ADC was observed as early as day 4 of the treatment, even though the tumor volume was still increasing. These observations suggested evolution of local necroses which were confirmed by histology. In a group of five tumor bearing rats, retrovirus-producing packaging cell injections were given intratumorally to mimic clinically relevant gene therapy. In these cases, only small and short-lasting T2 and ADC elevations were found following GCV treatment without an effect on the overall tumor growth and outcome. Our results show that quantitative magnetic resonance imaging including T2 and ADC, is superior to robust volume measurements in predicting an early response to retrovirus-mediated gene therapy in vivo.


Building research capacity at FQHCs: A model of support from the All of Us Research Program.
The All of Us Research Program is an historic effort to gather data over 10+ years from one million or more people living in the United States to accelerate research and advance precision medicine. There is a particular focus on populations historically underrepresented in biomedical research who are often served by Federally Qualified Health Centers (FQHCs). However, FQHCs face significant challenges in participating in research. This paper addresses three common barriers faced by FQHCs and describes a management model that was used to support a group of FQHCs participating in the All of Us Research Program. Specifically, the paper addresses the challenges of building FQHC research capacity to operationalize and manage research activities, transforming and sharing Electronic Health Records and other data, and recruiting and retaining research participants. The central coordination management model, which was used to support the FQHCs, is a generalizable framework and can serve as an exemplar of how to engage FQHCs in other longitudinal research efforts. To date, the FQHCs have enrolled more than 10,000 participants in the All of Us Research Program. Their success is an indicator that with the proper support, FQHCs can successfully implement a complex biomedical research program in the context of their health centers.


Neutrophilic eccrine hidradenitis secondary to topotecan.
Neutrophilic eccrine hidradenitis (NEH) is a self-restricted inflammatory condition, usually secondary to chemotherapeutic agents and less frequently to other drugs such as zidovudine or various infections. NEH clinical features include erythematous, occasionally painful nodules and plaques. Histological examinations reveal neutrophilic infiltrates and degeneration of eccrine glands. A 45-year-old female was treated with topotecan and colony-stimulating factor for ovarian cancer. The erythematous and slightly pruritic plaques on the upper and lower limbs and ear lobes appeared approximately 1 week after chemotherapy and spontaneously subsided in about 10 days, only to recur after the next drug dose. A skin biopsy revealed NEH; all skin cultures were negative. It is believed that this patient developed topotecan-induced NEH; this relationship with therapy rather than the underlying disease rules out a paraneoplastic reaction, and negative cultures excluded infectious causes. In addition, since skin lesions recurred after CSF was discontinued, this agent was not involved. Studies relating NEH to topotecan, a topoisomerasa I inhibitor, have not reported such an event in the literature.


Hetero-grafting affects flavonoid biosynthesis in sweet orange 'Newhall' (Citrus sinensis) peels: a metabolomics and transcriptomics analysis.
Citrus cultivation involves the widespread practice of grafting, which has a significant impact on citrus development and fruit quality and yield. However, understanding the effect of flavonoid compounds after different rootstock grafting have been limited. Flavonoid compounds, found at the highest levels in citrus peels, contribute to improving fruit quality and nutritional value. In this study, scion-rootstock interaction was investigated at various developmental stages when sweet orange 'Newhall' was hetero-grafted with two commonly used rootstocks (Poncirus trifoliate population, C. junos Siebold ex Tanaka). Physiological index detection showed a higher concentration of total flavonoid content in peels of sweet orange 'Newhall' grafted on Poncirus trifoliate population (ct) than C. junos Siebold ex Tanaka (cj). Further metabolomic analysis identified 703 flavonoid compounds, including flavones, flavonols, and flavanones. Out of the 25 flavonoids affected by different rootstock grafting and developmental stages, most were flavones. Transcriptomic analysis identified 8,562 differentially expressed genes (DEGs). Co-expression and Pearson's correlation analysis discovered six hub structure genes and 19 transcription factors (TFs) that affected flavonoid biosynthesis. In addition to increasing the transcript levels of genes that synthesize flavones, flavonols, and flavanones, the scion-rootstock interaction also affected the expression of many TFs. Taken together, our findings suggested that hetero-grafting could promote the accumulation of flavonoid compounds in citrus peels during the development stages. These results offered fresh perspectives on grafting's application usefulness and the enhancement of the accumulation of nutritive flavonoid components by grafting in citrus.


Trends in the epidemiology of purple urine bag syndrome: A systematic review.
Purple urine bag syndrome (PUBS) is rarely observed in clinical practice. The present study aimed to identify the epidemiological trends in PUBS in recent decades. A search of PubMed articles published between 1980 October and 2016 August was conducted, in which 106 articles (174 cases) described PUBS. Of these cases, 58 cases were excluded: 14 cases without mention of gender, 4 cases without description of age, 37 cases without mention of white blood cell (WBC) count, shock status, fever status or description of etiology, and 3 cases without information on mortality. The remaining 116 PUBS cases were collected and analyzed in the present study. The articles were divided into three groups by publication year: 1991 to 2000, 2001 to 2010 and 2011 to 2016. The χ2 test was used for statistical analysis, with P<0.05 (two-tailed) defined as the threshold for significance. Of the total enrolled cases, there were 47 men (40.5%) and 69 women (59.5%), with a mean age ± standard deviation of 75.6±12.8 years. Of these, 98 cases (84.5%) were elderly (≥65 years old). A total of 93.1% of cases had a urine pH >7 while 6.9% of cases had acidic urine (pH <7). Furthermore, although WBC count elevated progressively, the mortality rate of patients with PUBS decreased over subsequent decades. This necessitates the advancement of antibiotics and application of early goal-directed therapy. Additionally, the overall mortality rate of PUBS (1980-2016) was 6.8%, which decreased to 4.3% in the last 5 years (2011-2016). In conclusion, although PUBS has previously been considered a benign process in the majority of indwelling catheterized patients, emphasis is required on early examination and aggressive antibiotic administration.


Thermostable T Cell Multiepitope Nanoparticle Antigens Inducing Potent Immune Responses against the Swine Fever Virus.
African swine fever (ASF) is caused by the African swine fever virus (ASFV) and is a highly contagious, acute, febrile disease that has high morbidity and mortality rates in domestic and wild swine. However, a safe and effective vaccine against ASF remains unavailable as single antigens fail to provide sufficient protection. Therefore, a combination of multiple antigens with an efficient delivery system might be an alternative strategy. Herein, a de novo-designed antigen with multiple T-cell epitopes (TEPs) of ASFV was conjugated for surface display on self-assembled nanoparticles (NPs) of Aquifex aeolicus lumazine synthase (AaLS) and Quasibacillus thermotolerans encapsulin (QT) through the SpyCatcher/SpyTag system to construct nanovaccines (TEP-Spy-NPs). TEP-Spy-NPs exhibited significantly more thermal, storage, and freeze-thaw stability in comparison to TEP monomers. TEP-Spy-NPs were highly immunogenic and induced strong polyclonal antibody responses in mice and pigs. The specific antibody titers against the TEP of the TEP-Spy-AaLS and TEP-Spy-QT groups were significantly higher than those of the TEP monomer immune group after the second booster immunization. The antibody titer against TEP of the TEP-Spy-QT group was approximately twice that of the TEP-Spy-AaLS group in mice. ELISpot analysis demonstrated that more IFN-γ- and IL-2-secreting splenic lymphocytes were produced by TEP-Spy-AaLS- and TEP-Spy-QT-immunized mice than by TEP monomer-immunized mice. TEP-Spy-NPs elicited stronger cellular immunity and in vivo immunity in immunized pigs than did TEP monomers. Thus, the TEP nanovaccine successfully induced strong humoral and cellular immune responses in mice and pigs, and TEP-Spy-NPs have the potential as candidate vaccines for ASFV.


What makes Dutch youth comply with preventive COVID-19 measures? An explorative study.
The measures to contain the spread of COVID-19 are challenging for youth, especially the social isolation measures. These measures are antagonistic to healthy youth development, which requires sufficient social contact with peers and adults. This explorative study examined what factors are associated with adherence to COVID-19 measures in a sample of Dutch youth (N = 263; 79.8% female) with ages ranging between 16 and 24 years (M = 21.1 years; SD = 2.44 years), who completed an online questionnaire about their compliance to measures, resilience, coping strategies, mental health, and availability of a natural mentor. Results showed that youth with fewer depressive symptoms adhered better to measures of social distance. Youth who were less suspicious, more resilient, and those with an active coping strategy or a natural mentor more often complied with COVID-19 measures. These results can be used to help youth comply with the COVID-19 measures.


Pimasertib, a selective oral MEK1/2 inhibitor: absolute bioavailability, mass balance, elimination route, and metabolite profile in cancer patients.
This trial (NCT: 01713036) investigated the absolute bioavailability, mass balance and metabolite profile of pimasertib in a new design combining these investigations in a single group of patients. Six male patients with pathologically confirmed, locally advanced or metastatic solid tumours were enrolled. Exclusion criteria included Eastern Cooperative Oncology Group performance status >1. In Part A of the trial, patients received a 60 mg oral dose of unlabelled pimasertib followed by an intravenous (i.v.) tracer dose of [14 C]pimasertib 2 μg (equalling 9 kBq) as a bolus injection, one hour after the oral dose, on Day 1. On Day 8, all patients received 60 mg pimasertib capsules spiked with 2.6 MBq of [14 C]pimasertib. Patients received 60 mg oral unlabelled pimasertib twice daily from Day 3 to Day 21 of Part A and in subsequent 21-day cycles in Part B. Following i.v. administration, [14 C]pimasertib exhibited a geometric mean total body clearance of 45.7 l h-1 (geometric coefficient of variation [geometric CV]: 47.2%) and a volume of distribution of 229 l (geometric CV: 42.0%). Absolute bioavailability was 73%. The majority of the oral [14 C] dose (85.1%) was recovered in excreta. Total radioactivity was mainly excreted into urine (52.8%) and faeces (30.7%) with 78.9% of the [14 C] dose recovered as metabolites. Two major circulating metabolites were identified in plasma: a carboxylic acid (M445) and a phosphoethanolamine conjugate (M554). The safety profile was in line with the published pimasertib trials. Pimasertib showed a favourable pharmacokinetic profile with high absolute bioavailability and a unique metabolic pathway (conjugation with phosphoethanolamine).


A Two Question Screen for Mental Health Opportunities.
Shortened versions of validated PRO measures of coping strategies e.g. PSEQ-2, may facilitate screening and monitoring of psychological conditions such as depression and anxiety. The primary research question in this study assesses the sensitivity and specificity of a PSEQ-2 score of less than 10 for important symptoms of depression (a PHQ-2 score greater than 2), anxiety (GAD-2 score greater than 2), any impactful prior episode of psychological trauma, and QuickDASH greater than 49. Secondarily we assess the associations between self-efficacy and other demographic and psychological factors on the magnitude of limitations and pain intensity. We performed a retrospective PRO evaluation in 926 adult patients attending an upper extremity clinic between 1st January 2018 and 31st January 2019. Demographic factors were assessed using electronic medical records and PRO data using an online platform. Patients included 556 (60%) women, 370 (40%) men (mean 51 years ± 14 (range, 19-88), mostly (n=584, 63%) with safety net insurance. A PSEQ-2 scoring threshold of less than 10 was 81% sensitive for a PHQ-2 score of 3 or greater, 84% sensitive for a GAD-2 score of 3 or greater, 84% sensitive for one or more important psychological traumas, and 82% sensitive for a QuickDASH of 50 or greater. PSEQ-2 less than 10 was independently associated with greater upper extremity limitations (β=11 [6.3 to 17, 95% Confidence interval [C.I], P<0.001) and pain intensity (β=0.92 (0.31 to 1.5, 95% C.I) P=0.003) amongst other psychological and demographic factors. A PSEQ-2 score of less than 10 might, along with verbal and non-verbal signs of distress, be a useful way to introduce the use of more sensitive screening questionnaires about anxiety or depression, or open up the option of speaking directly to mental or social health professionals. Future studies are required to test this hypothesis.


Whole-brain connectivity to the bed nucleus of the stria terminalis calretinin-expressing interneurons in male mice.
The bed nucleus of the stria terminalis (BNST) is a neuropeptide-enriched brain region that modulates a wide variety of emotional behaviours and states, including stress, anxiety, reward and social interaction. The BNST consists of diverse subregions and neuronal ensembles; however, because of the high molecular heterogeneity within BNST neurons, the mechanisms through which the BNST regulates distinct emotional behaviours remain largely unclear. Prior studies have identified BNST calretinin (CR)-expressing neurons, which lack neuropeptides. Here, employing virus-based cell-type-specific retrograde and anterograde tracing systems, we mapped the whole-brain monosynaptic inputs and axonal projections of BNST CR-expressing neurons in male mice. We found that BNST CR-expressing neurons received inputs mainly from the amygdalopiriform transition area, central amygdala and hippocampus and moderately from the medial preoptic area, basolateral amygdala, paraventricular thalamus and lateral hypothalamus. Within the BNST, plenty of input neurons were primarily located in the oval and interfascicular subregions. Furthermore, numerous BNST CR-expressing neuronal boutons were observed within the BNST but not in other brain regions, thus suggesting that these neurons are a type of interneuron. These results will help further elucidate the neuronal circuits underlying the elaborate and distinct functions of the BNST.


Effect of revascularization of chronic total occlusion on tandem stenoses in a "donor" artery.
The presence, severity, and extent of ischemia predict the outcome of coronary artery disease. Indeed the extent of myocardial ischemia and viability determines the value of revascularization in coronary stenosis after acute myocardial infarction. In multivessel coronary artery disease, noninvasive methods for the evaluation of ischemia are often inadequate to guide percutaneous coronary intervention. It is a common misperception that revascularization might not benefit a myocardial segment in the chronic total occlusion distribution when that segment is supplied by well-developed collateral vessels, because severe ischemia is unlikely to be present under these circumstances. An 82-year-old man presented with acute coronary syndrome, tandem stenoses in a "donor" artery, and a chronic total occlusion of the right coronary artery. We present a rationale for using fractional flow reserve to determine the existence of ischemia and to aid in deciding the best approach to the treatment of that ischemia.


Microenvironmental regulation of tumour angiogenesis.
Tumours display considerable variation in the patterning and properties of angiogenic blood vessels, as well as in their responses to anti-angiogenic therapy. Angiogenic programming of neoplastic tissue is a multidimensional process regulated by cancer cells in concert with a variety of tumour-associated stromal cells and their bioactive products, which encompass cytokines and growth factors, the extracellular matrix and secreted microvesicles. In this Review, we discuss the extrinsic regulation of angiogenesis by the tumour microenvironment, highlighting potential vulnerabilities that could be targeted to improve the applicability and reach of anti-angiogenic cancer therapies.


A Study of 5-(1,2,4-Triazol-C-yl)tetrazol-1-ols: Combining the Benefits of Different Heterocycles for the Design of Energetic Materials.
The synthesis and full structural and spectroscopic characterization of three 5-(1,2,4-triazol-C-yl)tetrazol-1-ol compounds with selected energetic moieties including nitrimino (5), nitro (6) and azido (7) groups are reported. The influence of those energetic moieties as well as the C-C connection of a tetrazol-1-ol and a 1,2,4-triazole on structural and energetic properties has been investigated. All compounds were well characterized by various means, including IR and multinuclear NMR spectroscopy, mass spectrometry, and DSC. The molecular structures of 5-8 were determined in the solid state by single-crystal X-ray diffraction. The standard heats of formation were calculated on the CBS-4M level of theory utilizing the atomization energy method, revealing highly positive values for all compounds. The detonation parameters were calculated with the EXPLO5 program and compared to the common secondary explosive RDX. Additionally, sensitivities towards impact, friction and electrostatic discharge were determined.


Revisiting the role of spatial frequencies in the holistic processing of faces.
V. Goffaux and B. Rossion (2006) argued that holistic processing of faces is largely supported by low spatial frequencies (LSFs) but less so by high spatial frequencies (HSFs). We addressed this claim using a sequential matching task with face composites. Observers judged whether the top halves of aligned or misaligned composites were identical. We replicated the V. Goffaux and B. Rossion (2006) results, finding a greater alignment effect in accuracy for LSF compared with HSF faces on same trials. However, there was also a greater bias for responding "same" for HSF compared with LSF faces, indicating that the alignment effects arose from differential response biases. Crucially, comparable congruency effects found for LSF and HSF suggest that LSF and HSF faces are processed equally holistically. These results demonstrate that it is necessary to use measures that take response biases into account in order to fully understand the holistic nature of face processing.


Single brain metastasis of non-small cell lung carcinoma. Study of survival among 54 patients.
We studied 54 patients treated for non-small cell lung carcinoma with single brain metastasis presenting between 1980 and 1985. Better survival was obtained in cases of patients presenting a fair neurological condition who were treated by surgery. Histological condition and date of onet of metastasis had no significant influence on survival. Combined treatment of both primary lung tumour and brain metastasis was a favourable prognosis element, and surgical resection of both locations led to the best results in terms of duration and quality of survival.


Prevalence, Awareness, Treatment and Control of Diabetes in India From the Countrywide National NCD Monitoring Survey.
To determine the prevalence, awareness, treatment and control of diabetes mellitus (DM) and associated factors amongst adults (18-69 years) in India from the National Noncommunicable Disease Monitoring Survey (NNMS). NNMS was a comprehensive, cross-sectional survey conducted in 2017-18 on a national sample of 12,000 households in 600 primary sampling units. In every household, one eligible adult aged 18-69 years were selected. Information on NCD risk factors and their health-seeking behaviors were collected. Anthropometric measurements, blood pressure and fasting capillary blood glucose were measured. DM was defined as fasting blood glucose (FBG) ≥126 mg/dl including those on medication. Awareness, treatment, and control of DM were defined as adults previously diagnosed with DM by a doctor, on prescribed medication for DM, and FBG <126 mg/dl, respectively. The weighted data are presented as mean and proportions with 95% CI. We applied the Student t-test for continuous variables, Pearson's chi-square test for categorical variables and multivariate regression to determine the odds ratio. For statistical significance, a p-value < 0.05 was considered. Prevalence of DM and impaired fasting blood glucose (IFG) in India was 9.3% and 24.5% respectively. Among those with DM, 45.8% were aware, 36.1% were on treatment and 15.7% had it under control. More than three-fourths of adults approached the allopathic practitioners for consultation (84.0%) and treatment (78.8%) for diabetes. Older adults were associated with an increased risk for DM [OR 8.89 (95% CI 6.66-11.87) and were 16 times more aware of DM. Better awareness, treatment and control levels were seen among adults with raised blood pressure and raised cholesterol. The prevalence of DM and IFG is high among adults, while the levels of awareness, treatment and control are still low in India, and this varied notably between the age groups. Multifaceted approaches that include improved awareness, adherence to treatment, better preventive and counseling services are crucial to halt diabetes in India. Also, expanding traditional systems of medicine (Ayurveda, Yoga, Naturopathy, Unani, Siddha, and Homeopathy [AYUSH]) into diabetes prevention and control practices open solutions to manage this crisis.


Spontaneous non-aneurysmal popliteal artery dissection managed without operative treatment: A case report and literature review.
Primary arterial dissection in peripheral arteries of the extremities is exceedingly rare. Isolated dissection of peripheral arteries (femoropopliteal or popliteal) primarily has been reported in aneurysmal arteries. Spontaneous dissection limited to a non-aneurysmal popliteal artery was first described in 1999 by Rabkin et al. We report a case of a non-aneurysmal popliteal artery dissection to emphasize its rare condition. A 61-year-old man consulted because of sudden onset of pain and cramps in his left leg after walking 60 metres. A high-resolution duplex ultrasonography could identify a dissection of a non-aneurysmal popliteal artery. Computed tomography angiography could confirm the diagnosis. An operative repair was scheduled 3 weeks later and the patient was put on antiplatelet medication (acetylsalicylic acid 80 mg 1x/day) in the meantime. After 3 weeks the dissection was resolved spontaneously and the patient didn't undergo surgery. Check-ups remained reassuring and we scheduled a duplex ultrasonography within one year. Antiplatelet medication was continued. Spontaneous dissection limited to a non-aneurysmal popliteal artery is extremely rare. Diagnosis can be made by duplex ultrasonography and/or CT angiography. Treatment options consist of conservative management or operative treatment. Operative treatments consist of an open repair with bypass or interposition graft or minimal invasive endovascular stent grafting. A standardized protocol for conservative treatment in this specific condition is not available. Annual follow-up of these patients is essential.


Multiple phosphorylation events control chicken ovalbumin upstream promoter transcription factor I orphan nuclear receptor activity.
Chicken ovalbumin upstream promoter transcription factor I (COUP-TFI) is an orphan member of the nuclear hormone receptor superfamily that comprises key regulators of many biological functions, such as embryonic development, metabolism, homeostasis, and reproduction. Although COUP-TFI can both actively silence gene transcription and antagonize the functions of various other nuclear receptors, the COUP-TFI orphan receptor also acts as a transcriptional activator in certain contexts. Moreover, COUP-TFI has recently been shown to serve as an accessory factor for some ligand-bound nuclear receptors, suggesting that it may modulate, both negatively and positively, a wide range of hormonal responses. In the absence of any identified cognate ligand, the mechanisms involved in the regulation of COUP-TFI activity remain unclear. The elucidation of several putative phosphorylation sites for MAPKs, PKC, and casein kinase II within the sequence of this orphan receptor led us to investigate phosphorylation events regulating the various COUP-TFI functions. After showing that COUP-TFI is phosphorylated in vivo, we provide evidence that in vivo inhibition of either MAPK or PKC signaling pathway leads to a specific and pronounced decrease in COUP-TFI-dependent transcriptional activation of the vitronectin gene promoter. Focusing on the molecular mechanisms underlying the MAPK- and PKC-mediated regulation of COUP-TFI activity, we show that COUP-TFI can be directly targeted by PKC and MAPK. These phosphorylation events differentially modulate COUP-TFI functions: PKC-mediated phosphorylation enhances COUP-TFI affinity for DNA and MAPK-mediated phosphorylation positively regulates the transactivation function of COUP-TFI, possibly through enhancing specific coactivator recruitment. These data provide evidence that COUP-TFI is likely to integrate distinct signaling pathways and raise the possibility that multiple extracellular signals influence biological processes controlled by COUP-TFI.


Altered gene expression of cytokine, ICAM-1, and class II molecules precedes mouse intestinal allograft rejection.
Rapid and severe rejection remains a major obstacle to successful clinical intestinal transplantation (IT). The aggressive nature of rejection in IT has been attributed to the increased massive immune stimulus provided by large numbers of resident lymphocytes, antigen presentation capacity of enterocytes, and graft damage mediated by luminal microflora. Early small bowel expression of proinflammatory cytokines, MHC class II, and adhesion molecules may also promote IT rejection, but the lack of a mouse model has hampered extensive studies of gene expression in IT. Using a recently developed surgical model, we examined the temporal pattern of gene expression in CB6F1 (H-2b/d) vascularized, heterotopic intestinal allografts transplanted into BALB/c (H-2d) mice. Although histological evidence of rejection was not present until day 7 in allografts, Northern blot analysis demonstrated increases in TNF alpha gene transcripts as early as day 3, followed by the expression of IL-1 beta, intercellular adhesion molecule-1, and MHC class II by day 5. Using reverse-transcriptase polymerase chain reaction, IFN-gamma was detected in allografts by day 3 and persisted to day 10. In contrast, IL-2, IL-4, IL-5, and IL-6 mRNA transcripts peaked by day 5 and then decreased, suggesting that both Th1 and Th2 subsets are involved in the rejection of unmodified small bowel allografts. The early and progressive expression of TNF alpha and IL-1 beta as well as IFN-gamma, intercellular adhesion molecule-1, and MHC class II in IT rejection may contribute to the difficulty in controlling IT rejection with present immunosuppression.


The effect of blood transfusion on cerebral blood-flow in preterm infants: a Doppler study.
Stable infants with anaemia needing a transfusion with adult red blood-cells were studied to elucidate changes in brain blood-flow velocity. Within 24 hours and at five to six days following transfusion a substantial mean flow velocity reduction was observed. Haemodynamic factors contributing to the reduction were an increase in cerebrovascular resistance and an increase in whole blood viscosity, as reflected by a raised pulsatility index. Transfusion with adult red blood-cells causes an elevation in haemoglobin concentration, thereby increasing the total oxygen-carrying capacity of arterial blood; however, this lowers the concentration of fetal haemoglobin which possesses a higher affinity for oxygen. Since cerebral oxygen transport is equal to the product of cerebral blood-flow and arterial oxygen content, this finding suggests the existence of a homeostatic mechanism for cerebral oxygen transport. The actual amount of cerebral oxygen transport was found to increase progressively as the percentage of fetal haemoglobin rose above 30 per cent. At higher fetal haemoglobin levels, appropriate elevations in cerebral blood-flow occurred, causing an increase in the supply of oxygen to the brain.


Activation of the kynurenine pathway predicts poor outcome in patients with clear cell renal cell carcinoma.
To investigate the expression of the kynurenine (KYN) pathway components and the prognostic role of the KYN-to-tryptophan ratio (KTR) in a cohort of patients with clear cell renal cell carcinoma (ccRCC). The expression of KYN pathway components was investigated by tissue microarray-based immunohistochemistry, indirect immunofluorescence, and confocal microscopy analysis in 100 ccRCC cases and 30 normal renal samples. The role of this pathway in sustaining cancer cell proliferation, migration, and chemoresistance was evaluated. In addition, tryptophan and KYN concentrations and their ratio were measured in serum of 195 patients with ccRCC using a sandwich enzyme-linked immunosorbent assay. The role of KTR as a prognostic factor for ccRCC cancer-specific survival (CSS) and progression-free survival (PFS) was assessed. Tissue microarray-based immunohistochemistry and indirect immunofluorescence staining showed an increased signal for KYN pathway components in ccRCC. Kaplan-Meier curves showed significant differences in CSS and PFS among groups of patients with high vs. low KTR. In particular, patients with high KTR values had a 5-year survival rate of 76.9% as compared with 92.3% for subjects with low levels (P < 0.0001). Similar findings were observed for PFS (72.8% vs. 96.8% at 5y). At multivariate analysis, KTR was an independent adverse prognostic factor for CSS (hazard ratio = 1.24, P = 0.001), and PFS (hazard ratio = 1.14, P = 0.001). The involvement of the KYN pathway enzymes and catabolites in ccRCC occurs via both immune and nonimmune mechanisms. Our data suggest that KTR could serve as a marker of ccRCC aggressiveness and as a prognostic factor for CSS and PFS.


Characterization and functional analysis of hypoxia-inducible factor HIF1α and its inhibitor HIF1αn in tilapia.
Hypoxia is a major cause of fish morbidity and mortality in the aquatic environment. Hypoxia-inducible factors are very important modulators in the transcriptional response to hypoxic stress. In this study, we characterized and conducted functional analysis of hypoxia-inducible factor HIF1α and its inhibitor HIF1αn in Nile tilapia (Oreochromis niloticus). By cloning and Sanger sequencing, we obtained the full length cDNA sequences for HIF1α (2686bp) and HIF1αn (1308bp), respectively. The CDS of HIF1α includes 15 exons encoding 768 amino acid residues and the CDS of HIF1αn contains 8 exons encoding 354 amino acid residues. The complete CDS sequences of HIF1α and HIF1αn cloned from tilapia shared very high homology with known genes from other fishes. HIF1α show differentiated expression in different tissues (brain, heart, gill, spleen, liver) and at different hypoxia exposure times (6h, 12h, 24h). HIF1αn expression level under hypoxia is generally increased (6h, 12h, 24h) and shows extremely highly upregulation in brain tissue under hypoxia. A functional determination site analysis in the protein sequences between fish and land animals identified 21 amino acid sites in HIF1α and 2 sites in HIF1αn as significantly associated sites (α = 0.05). Phylogenetic tree-based positive selection analysis suggested 22 sites in HIF1α as positively selected sites with a p-value of at least 95% for fish lineages compared to the land animals. Our study could be important for clarifying the mechanism of fish adaptation to aquatic hypoxia environment.


Two cases of hereditary diabetes insipidus, with an autopsy finding in one.
Two cases of hereditary diabetes insipidus (DI) are described, with an autopsy finding in one. The patients were brothers and 7 other relatives had symptoms of DI. The transmission of the disease in this family seemed to be an autosomal dominant trait with incomplete penetration. Both patients had the incomplete type of DI, which is diagnosed by the response of plasma AVP and the change in Uosm/Posm to 14 h water deprivation. The post-mortem examination in Case 1 showed that there was no atrophy of the supraoptic nucleus and paraventricular nucleus, but immunohistochemical studies revealed, that the paraventricular nucleus scarcely had any vasopressin positive cells in contrast to an autopsy control. This finding suggests that there may be a congenital defect in AVP synthesis in some cases of hereditary DI.


Deblurring of x-ray spectra acquired with a Nal-photomultiplier detector by constrained least-squares deconvolution.
A constrained least-squares technique to correct diagnostic x-ray tube energy spectra for inherent blurring by scintillation detectors was developed. The measured detector response function to monoenergetic sources was used to construct a matrix that modeled the energy broadening in the crystal. This blurring operator, along with an estimate of statistical noise in the count data, comprised the a priori system knowledge required for application of the method. Tungsten anode spectra up to 90 kVp were acquired with a Nal-photomultiplier detector system at a source-to-detector distance of 30 cm. X-ray tube output was collimated at the detector by a 0.5 mm diameter pinhole collimator. Measured Nal spectra were compared to both published reference data and to spectra acquired in our laboratory with a Ge detector system. Application of the constrained least-squares technique involved first defining a criterion function that combined an assessment of the goodness of fit with a weighted measure of the smoothness of the solution. Minimization of this function resulted in the corrected spectrum. While it is not possible to recover the characteristic tungsten peaks, the success of our method in deconvolving the measured spectra was demonstrated by a significant improvement in agreement with reference data. To provide a measure of this agreement, a histogram of the differences between the two curves was generated. The full width at half maximum (FWHM) of the Gaussian distribution fit to the histogram was used to quantify the similarity between the spectra and the reference data, both before and after correction. As spectral agreement improves, the FWHM becomes smaller. We show that application of the constrained least-squares technique improved spectral matching by 20%-60%.


Tricuspid regurgitation, right ventricular function, and renal congestion: a cardiorenal triangle.
There is a growing interest in the evaluation of tricuspid regurgitation due to its increasing prevalence and detrimental impact on clinical outcomes. Historically, it has been coined the "forgotten" defect in the field of valvular heart disease due to the lack of effective treatments to improve prognosis. However, the development of percutaneous treatment techniques has led to a new era in its management, with promising results and diminished complication risk. In spite of these advances, a comprehensive exploration of the pathophysiological mechanisms is essential to establish clear indications and optimal timing for medical and percutaneous intervention. This review will address the most important aspects related to the diagnosis, pathophysiology and treatment of tricuspid regurgitation from a cardiorenal perspective, with a special emphasis on the interaction between right ventricular dysfunction and the development of hepatorenal congestion.


Visualization and analysis of co-occurrence and cross-tabulation data in medical research.
Analyzing raw data can be prohibitively time consuming. A variety of graphical techniques have been developed to address this problem. Although graphical analysis can provide a simple yet comprehensive overview of a large dataset, often these techniques fail to capture the essence of data trends. In addition, the ability to easily query any component of the data subset frequently remains burdensome. In this paper, we present a general method to address these issues for cross-tabulation tables and provide examples of their use in medical research.


AIMSWISS-Ab initio multiple spawning with informed stochastic selections.
Ab initio multiple spawning (AIMS) offers a reliable strategy to describe the excited-state dynamics and nonadiabatic processes of molecular systems. AIMS represents nuclear wavefunctions as linear combinations of traveling, coupled Gaussians called trajectory basis functions (TBFs) and uses a spawning algorithm to increase as needed the size of this basis set during nonadiabatic transitions. While the success of AIMS resides in this spawning algorithm, the dramatic increase in TBFs generated by multiple crossings between electronic states can rapidly lead to intractable dynamics. In this Communication, we introduce a new flavor of AIMS, coined ab initio multiple spawning with informed stochastic selections (AIMSWISS), which proposes a parameter-free strategy to beat the growing number of TBFs in an AIMS dynamics while preserving its accurate description of nonadiabatic transitions. The performance of AIMSWISS is validated against the photodynamics of ethylene, cyclopropanone, and fulvene. This technique, built upon the recently developed stochastic-selection AIMS, is intended to serve as a computationally affordable starting point for multiple spawning simulations.


Selection and Validation of Appropriate Reference Genes for Quantitative Real-Time PCR Normalization in Staminate and Perfect Flowers of Andromonoecious Taihangia rupestris.
Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) is the most commonly used and powerful method for gene expression analysis due to its high sensitivity, specificity, and high throughput, and the accuracy of this approach depends on the stability of reference genes used for normalization. Taihangia rupestris Yu and Li (Rosaceae), an andromonoecious plant, produces both bisexual flowers and unisexual male flowers within the same individual. Using qRT-PCR technique, investigation of the gene expression profiling in staminate and perfect flowers would improve our understanding of the molecular mechanism in regulation of flower formation and sex differentiation in andromonoecious T. rupestris. To accurate normalize the gene expression level in Taihangia flower, 16 candidate reference genes, including 10 traditional housekeeping genes, and 6 newly stable genes, were selected based on transcriptome sequence data and previous studies. The expressions of these genes were assessed by qRT-PCR analysis in 51 samples, including 30 staminate and perfect flower samples across developmental stages and 21 different floral tissue samples from mature flowers. By using geNorm, NormFinder, BestKeeper, and comprehensive RefFinder algorithms, ADF3 combined with UFD1 were identified as the optimal reference genes for staminate flowers, while the combination of HIS3/ADF3 was the most accurate reference genes for perfect floral samples. For floral tissues, HIS3, UFD1, and TMP50 were the most suitable reference genes. Furthermore, two target genes, TruPI, and TruFBP24, involved in floral organ identity were selected to validate the most and least stable reference genes in staminate flowers, perfect flowers, and different floral tissues, indicating that the use of inappropriate reference genes for normalization will lead to the adverse results. The reference genes identified in this study will improve the accuracy of qRT-PCR quantification of target gene expression in andromonoecious T. rupestris flowers, and will facilitate the functional genomics studies on flower development and sex differentiation in the future.


[Os lunatum partitum: critical comment on the contribution of C.Hoffmann].
This paper refers to the case published in "Handchirurgie" 14, 109-113 (1982). The author has conducted a critical analysis of the original records and of the literature. He concludes that the diagnosis is one of necrosis of the lunate (Kienböck's disease), not os lunatum partitum.


Durability of Pt/graphitized carbon catalysts for the oxygen reduction reaction prepared by the nanocapsule method.
Monodisperse Pt nanoparticles supported on a graphitized carbon black (GC; 150 m(2) g(-1)), which exhibits higher resistance to carbon corrosion than a conventional high-surface-area carbon black (CB; 800 m(2) g(-1)), were prepared by the nanocapsule method. Three kinds of 50 wt%-Pt loaded catalysts (our nanocapsule Pt/GC, a commercial Pt/GC, and a commercial Pt/CB) were subjected to the durability test by a standard potential step protocol (E = 0.9 V <--> 1.3 V vs. RHE, holding 30 s at each E, 1 min for one cycle) in N(2)-saturated 0.1 M HClO(4) solution at 25 degrees C. The oxygen reduction reaction (ORR) activities at these catalysts were evaluated from the hydrodynamic voltammograms in O(2)-saturated 0.1 M HClO(4) solution at 25 degrees C by the rotating ring-disk electrode technique. The kinetically-controlled mass activities (MA) for the ORR at these catalysts at E = 0.85 to 0.70 V vs. RHE were found to decrease in proportion to log [number of potential step cycles] from 100 to 5000 cycles. It was found that our nanpcapsule Pt/GC showed the highest durability; the time elapsed for the reduction of MA(0.8V) to 700 A g(-1) (ca. 1/2 of the initial MA(0.8V)) at our Pt/GC was 30 and 60 times longer than those for the commercial Pt/GC and Pt/CB, respectively. It was found that the most important factor leading to both high MA and high durability is highly dispersed state of Pt nanoparticles with uniform size over the whole surface of the corrosion-resistant GC support, to which our nanocapsule method has contributed greatly.


Giant neutrophils with increased peroxidase activity. Another evidence of dysgranulopoiesis in AIDS.
Using the automated hematologic analyzer Technicon H6000, which classifies leukocytes by their size and peroxidase activity, the authors have observed in nine patients with full-blown acquired immune deficiency syndrome (AIDS) a consistent increase in peroxidase content of circulating neutrophils. The increase in peroxidase activity was homogeneous in three patients (P less than 0.05). The most striking finding, however, was the occurrence of single abnormal neutrophils with peroxidase activity higher than the major neutrophil population (i.e., HPX [high peroxidase] cells). The importance of this phenomenon was correlated with the clinical status, higher HPX values being found in patients with more advanced disease. These instrumental observations were associated with the morphologic finding of atypical neutrophils, much larger than normal, with irregular nuclei and abundant cytoplasm filled with peroxidase-positive granulations. Such cells represent, in the authors' experience, the most common expression of dysgranulopoiesis in AIDS.


Depression in women treated for gynecological cancer: clinical and neuroendocrine assessment.
To determine the prevalence of major depression in cancer patients and assess the usefulness of the dexamethasone suppression test (DST) and the thyrotropin-releasing hormone (TRH) stimulation test for diagnosing major depression in these patients, the authors studied 83 women hospitalized for gynecological cancer. Nineteen (23%) had major depression according to DSM-III criteria. The sensitivity and specificity of the DST were 40% and 88%, respectively. No relationship between DST and TRH test results was found. These findings indicate a high prevalence of depression in cancer patients, but further research on these tests in cancer patients is needed; their routine use with cancer patients is premature at this time.


Laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) for refractory malignant ascites in patients unsuitable for cytoreductive surgery.
Malignant ascites (MA) is the abnormal accumulation of fluid in the peritoneal cavity of patients with intraperitoneal dissemination of their disease and is associated with a short life expectancy. The most common clinical feature is a progressive increase of abdominal distention resulting in pain, discomfort, anorexia and dyspnoea. Currently, no treatment is established standard of care due to limited efficacy or considerable toxicity. The objective was to examine the efficacy of laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) in the palliation of refractory MA in patients who were unsuitable for cytoreductive surgery. From May 2009 to June 2015, 12 patients with MA due to their peritoneal malignancy were treated with laparoscopic HIPEC. The time between operation and repeat paracentesis, in-hospital data, and the proportion of patients that did not require repeat paracentesis was analyzed. One patient (8%) was admitted to ICU for 1 day. The mean operating time and hospital stay was 149.3 min (range 79-185) and 4.6 days (range 2-11) respectively. Neither high-grade morbidity nor mortality was observed. The median OS was 57 days. In our experience, a complete and definitive disappearance of MA was observed in 83% of patients. Two patients (17%) developed recurrent MA 124 days and 283 days post-HIPEC. Laparoscopic HIPEC is a beneficial treatment for the management and palliation of refractory MA and results in an excellent clinical and radiological resolution in patients with a complete resolution observed in selected patients.


Three-dimensional organization of pKi-67: a comparative fluorescence and electron tomography study using FluoroNanogold.
The monoclonal antibody (MAb) Ki-67 is routinely used in clinical studies to estimate the growth fraction of tumors. However, the role of pKi-67, the protein detected by the Ki-67 MAb, remains elusive, although some biochemical data strongly suggest that it might organize chromatin. To better understand the functional organization of pKi-67, we studied its three-dimensional distribution in interphase cells by confocal microscopy and electron tomography. FluoroNanogold, a single probe combining a dense marker with a fluorescent dye, was used to investigate pKi-67 organization at the optical and ultrastructural levels. Observation by confocal microscopy followed by 3D reconstruction showed that pKi-67 forms a shell around the nucleoli. Double labeling experiments revealed that pKi-67 co-localizes with perinucleolar heterochromatin. Electron microscopy studies confirmed this close association and demonstrated that pKi-67 is located neither in the fibrillar nor in the granular components of the nucleolus. Finally, spatial analyses by electron tomography showed that pKi-67 forms cords 250-300 nm in diameter, which are themselves composed of 30-50-nm-thick fibers. These detailed comparative in situ analyses strongly suggest the involvement of pKi-67 in the higher-order organization of perinucleolar chromatin.


Hypoxia-related risk factors for death by suicide in a national clinical sample.
The relationship between three markers of chronic hypoxia (altitude, smoking and chronic obstructive pulmonary disease (COPD)) and suicide risk has not been well-studied. We conducted a population-based cohort study evaluating the association between chronic hypoxia and suicide risk. Patients entered the cohort in their first year with a documented healthcare encounter and remained in the cohort until their death or the end of the study period. Generalized estimating equation (GEE) methodology was used to assess the association between suicide and three risk markers of chronic hypoxia. Findings were summarized using odds ratio (OR) and 95% confidence intervals (CI). Among the 9,620,944 patients in the cohort, there were 22,403 suicide deaths. There was a statistically significant progression of suicide risk as altitude rose in increments of 1000 m (OR: 1.22). There was a strong association between the number of hypoxic conditions and the odds of suicide. Patients with three markers of chronic hypoxia was nearly four times more likely to die by suicide than patients with no markers (OR: 3.96). Chronic hypoxia is a risk factor for suicide and having multiple indicators of hypoxia confers a greater risk for suicide, indicating a dose-response relationship.


Differential recruitment of pre-mRNA splicing factors to alternatively spliced transcripts in vivo.
Alternative splicing in mammalian cells has been suggested to be largely controlled by combinatorial binding of basal splicing factors to pre-mRNA templates. This model predicts that distinct sets of pre-mRNA splicing factors are associated with alternatively spliced transcripts. However, no experimental evidence for differential recruitment of splicing factors to transcripts with distinct splicing fates is available. Here we have used quantitative single-cell imaging to test this key prediction in vivo. We show that distinct combinations of splicing factors are recruited to sites of alternatively spliced transcripts in intact cells. While a subset of serine/arginine protein splicing factors, including SF2/ASF, SC35, and SRp20, is efficiently recruited to the tau gene when exon 10 is included, these factors are less frequently associated with tau transcription sites when exon 10 is excluded. In contrast, the frequency of recruitment of several other splicing factors is independent of splicing outcome. Mutation analysis of SF2/ASF shows that both protein-protein as well as protein-RNA interactions are required for differential recruitment. The differential behavior of the various splicing factors provides the basis for combinatorial occupancy at pre-mRNAs. These observations represent the first in vivo evidence for differential association of pre-mRNA splicing factors with alternatively spliced transcripts. They confirm a key prediction of a stochastic model of alternative splicing, in which distinct combinatorial sets of generic pre-mRNA splicing factors contribute to splicing outcome.


alpha1-Antitrypsin deficiency presenting with panniculitis and incidental discovery of chronic obstructive pulmonary disease.
A 60-year-old man presented to the Emergency Department (ED) with large, painful, indurated plaques on the right thigh, left abdomen, left chest, and right chest, which began without any preceding trauma on the right thigh 3 weeks prior to presentation in the ED. He was initially treated with cefazolin 1 g three times daily as home infusions. When the lesions continued to progress, he was admitted to the hospital and placed on amoxicillin/clavulanate and vancomycin. He had a single episode of fever of 102 degrees F, but his white blood cell count and differential remained normal. An initial biopsy showed a dermal inflammatory infiltrate composed primarily of neutrophils and eosinophils with rare flame figures in the dermis. There was minimal fat seen in this biopsy. A differential diagnosis of Wells or Sweet's syndrome was entertained, and he was placed on 60 mg/day prednisone with no resolution of his symptoms. The patient's past medical history included hypertension, hyperlipidemia, peripheral neuropathy, and hiatal hernia. His family history was significant for emphysema in both parents and coronary artery disease in his father. Both of his parents smoked cigarettes. His grandfather, who was a coal miner, also had emphysema. Whilst on antibiotics and prednisone, the plaques on the patient's right thigh, right abdomen, and left chest expanded and ulcerated, draining an oily liquid (Figs 1 and 2). An incisional biopsy was obtained from his thigh. Histopathology showed a septal and lobular panniculitis with fat necrosis, neutrophils, and histiocytes (Fig. 3). Special stains for organisms were negative. Tissue sent for bacterial and fungal culture had no growth. Amylase and lipase levels were normal. Rheumatoid factor, antinuclear antibody (ANA), antineutrophil cytoplasmic antibody (ANCA), cryoglobulins, and antiphospholipid antibodies were all normal. The alpha1-antitrypsin level was low at 25 mg/dL (ref. 75-135). The alpha1-antitrypsin phenotype was PiZZ. The patient had a normal glucose-6-phosphate dehydrogenase level and was placed on dapsone 200 mg/day. The inflammation resolved and, over the course of several months, the involved areas healed with scarring. The patient denied any pulmonary complaints but, during his hospitalization, was found incidentally to have an oxygen saturation of 88% on room air. He was sent for evaluation by a pulmonologist, and pulmonary function tests revealed a mixed restrictive and obstructive pattern with a forced expiratory volume in 1 to forced vital capacity (FEV(1)/FVC) ratio of 63% of predicted. He had never smoked. He was placed on supplemental oxygen but, as his pulmonary disease has been stable, he has not been treated with intravenous antitrypsin inhibitor.


[Role of leukotriene antagonists in non-asthmatic disorders].
It has been shown that the leukotriens play a role in the pathobiologic process of allergic asthma and wheezing due to infection. Their specific role in other respiratory disorders or in other diseases is not yet fully understood. A recent consensus has elaborated the guidelines for the treatment of asthma in the paediatric age. According to these guidelines, the leukotriene-antagonists are recommended as a possible alternative to inhaled corticosteroids in the long-term treatment of mild persistent asthma. The association of antileukotrienes with the usual classical therapy led to a great improvement in the treatment of the most severe forms of the disease. Moreover, a growing number of disorders such as allergic rhinitis, chronic urticaria, atopic dermatitis and nasal polyposis seem to benefit from the use of these new drugs. In allergic rhinitis, the most common allergic disorder, the leukotrienes seem to be, together with histamine, important mediators of both the early and late stage of the allergic reaction. They seem to be responsible for the vasodilation and therefore for the nasal obstruction. There is a production of leukotrienes also in chronic urticaria, which is more frequent in adults, and in atopic dermatitis, which usually has its onset in the paediatric age. This paper summarizes the results of several clinical trials evaluating the therapeutical efficacy and safety of the leukotriene-antagonists. Despite the promising results, further studies are however necessary on a greater number of patients before recommending the use of this type of drug in this kind of disorders.


'Collective fictions': similarities in reasons for accepting maternal serum alpha-fetoprotein screening among women of diverse ethnic and social class backgrounds.
We analyzed the decisions of an ethnically and socioeconomically diverse group of women to accept or refuse a prenatal diagnostic test. We found that how women were informed about the test and the kind of information they were given determined their decisions more than their ethnic or social class background. To explain this, we argue that the women and their health care providers created a 'collective fiction' which situated the testing within the domain of routine prenatal care and denied its central connection to selective abortion and its eugenic implications.


Development and implementation of a nutrition education program for medical students: a new challenge.
Teaching nutrition to medical students is constrained by limitations in curricular time and competition with other topics. To identify time slots and teaching methods for incorporating nutrition into the medical school curriculum, determine students' nutritional knowledge following the program, and their perception of the effectiveness of the program. A nutritional workshop was added to the clinical experience weeks of second-year medical students. The first class included 66 students and the second class included 56 students. In order to fully acquaint the students with nutrition, four topics were included: nutritional policy, dietary assessment, nutritional recommendations, and obesity. Students were encouraged to actively participate in the program which included dietary intake interviews, debates regarding nutritional treatments, and actual practice in class. The main outcome measures were nutritional knowledge and evaluation of the program by the students. Over 90% of the students answered the knowledge questions correctly. The effectiveness of the training was graded (on a scale of 1-7) between 3.7-5.4 in the first year and 3.4-5.7 in the second year. The ten-hour nutritional workshops within the clinical weeks were well-received by second-year medical students. Using cases relevant to the students' age seems to enhance their interest in the program.


Pre-operative mediastinal evaluation in primary bronchial carcinoma--a review of staging investigations.
A review of staging investigations in the preoperative evaluation of mediastinal involvement in primary bronchial carcinoma is presented. The following conclusions are offered as guidelines for the use of mediastinal staging procedures in clinical practice: Surgical staging methods have the over-riding advantage of superior specificity over indirect imaging techniques. Where 67Ga-imaging or CT scanning are not available, routine pre-operative mediastinoscopy or, when appropriate, mediastinotomy will identify most patients with non-resectable disease but this approach entails a high proportion of true negative examinations. Radioisotope ventilation and perfusion lung imaging has no place in the pre-operative staging of lung cancer. Where the techniques are available, 67Ga-imaging and CT scanning have a use in selecting patients for mediastinal exploration. A negative mediastinal 67Ga scan or a negative CT examination suggest that mediastinal exploration will be unrewarding in the vast majority of cases and may be omitted prior to thoracotomy. A positive mediastinal 67Ga scan or the demonstration of abnormal mediastinal nodes by CT is an indication for mediastinal exploration which, if negative should be followed by thoracotomy.


Emergence of vaccine-derived poliovirus type 2 after using monovalent type 2 oral poliovirus vaccine in an outbreak response, Philippines.
In response to an outbreak of circulating vaccine-derived poliovirus (cVDPV) type 2 in the Philippines in 2019-2020, several rounds of supplementary immunization activities using the monovalent type 2 oral poliovirus vaccine (OPV) were conducted for the first time in the Western Pacific Region. After use of the monovalent vaccine, the emergence of vaccine-derived poliovirus unrelated to the outbreak virus was detected in healthy children and environmental samples. This report describes the detection of this poliovirus in the Philippines after use of the monovalent type 2 OPV for outbreak response. We describe the emergence of vaccine-derived poliovirus unrelated to the outbreak detected after supplementary immunization activities using the monovalent type 2 OPV. This analysis included virus characterization, phylogenetic analyses and epidemiological investigations. Three environmental samples and samples from six healthy children tested positive for the emergent vaccine-derived poliovirus. All isolates differed from the Sabin type 2 reference strain by 6-13 nucleotide changes, and all were detected in the National Capital Region and Region 4, which had conducted supplementary immunization activities. Since the 2016 removal of type 2 strains from the OPV, vaccine-derived poliovirus outbreaks have occurred in communities that are immunologically naive to poliovirus type 2 and in areas with recent use of monovalent OPV. To prevent the emergence and further spread of cVDPV type 2, several interventions could be implemented including optimizing outbreak responses by using the monovalent type 2 OPV, accelerating the availability of the novel type 2 OPV, strengthening routine immunization using inactivated polio vaccine and eventually replacing OPV with inactivated poliovirus vaccine for routine immunization.


'Who else is in the drawer?' Trauma, personhood and prophylaxis among Cuban scientific spiritists.
In this paper the author explores notions of illness and health among a particular group of spirit mediums in Havana: the Sociedad de Estudios Psicologicos Amor y Caridad Universal. For its members and leaders, the development of mediumship is not just therapeutic but prophylactic. And traumas (of spirits and persons) must not simply be acknowledged but metabolised through the execution of good mediumship. More importantly, people's existences are chemically and psychologically entangled with those of their protective spirits, making of their 'selves' systems, rather than bounded essences. The author argues that such concepts of personhood offer alternative modes of understanding the self in relation to forms of otherness, including dysfunction and pathology.


Intestinal ischemia following laparoscopic surgery: a case series.
Intestinal ischemia is a rare complication of laparoscopic surgery. Its prognosis depends on a high index of suspicion and effective early treatment. In the present report, we describe three cases where intestinal ischemia developed following laparoscopic surgery. Case 1 concerns a 52-year-old Caucasian man who developed large bowel ischemia following laparoscopic adjustable gastric band surgery. Case 2 concerns an 82-year-old Caucasian woman who developed fatal intestinal ischemia following laparoscopic cholecystectomy. Case 3 concerns a 58-year old Caucasian woman who developed right-sided lower intestinal ischemia following open cholecystectomy. Intestinal ischemia is a rare complication of laparoscopic surgery. The identification of high-risk patients is an essential primary preventive measure. A high index of suspicion is required to make an early diagnosis, which may help improve outcomes.


Delirium and sleep disturbances-A narrative review.
Delirium is considered a severe complication. It increases morbidity and mortality and represents a major financial burden for healthcare systems. Thus, prevention becomes a focal point of research. Sleep disturbances have been linked to the occurrence of delirium. Consequently, several interventions that target a possible connection have been studied in recent years. This narrative literature review explores the published data for an association between delirium and different types of sleep disturbances, the pathophysiological interactions and prevention methods. A literature search was carried out utilizing PubMed, the Cochrane Library, Livivo and Google Scholar. Although an association between several types of sleep disturbances and delirium has been shown, no causality has been proven so far. Nevertheless, several pharmacological and nonpharmacological interventions for delirium prevention have been attempted; however, the level of evidence is insufficient at this point. Further research is required to prove causality between sleep disturbances and delirium. Nonpharmacological interventions should be used in construction and maintenance of intensive care units and hospitals. Pharmacological interventions could be effective for prevention but further research is needed. Screening patients at risk of delirium for sleep disturbances and antihistaminergic/anticholinergic medication seems beneficial.


[Ano-rectal abnormalities and esophageal atresia; familial and epidemiological studies].
The authors estimate the frequency of anorectal malformations (0.30 p. 1,000) and oesophageal atresia (0.20 p. 1,000) and record an increase in the sex-ratio along with a high percentage of associated malformations. From the available data and a family study on 366 anorectal malformations and 327 oesophageal atresia, they suggest the possibility of a dominant autosomal inheritance with weak penetrance, in certain cases of anorectal malformations and of a polygenic heredity in oesophageal atresia. The findings do not allow to reassure the parents completely of the sporadic cases, since the recurrence risk is 1-2 p. 100.


Entropy and enthalpy of interaction between amino acid side chains in nanopores.
Understanding the stabilities of proteins in nanopores requires a quantitative description of confinement induced interactions between amino acid side chains. We use molecular dynamics simulations to study the nature of interactions between the side chain pairs ALA-PHE, SER-ASN, and LYS-GLU in bulk water and in water-filled nanopores. The temperature dependence of the bulk solvent potentials of mean force and the interaction free energies in cylindrical and spherical nanopores is used to identify the corresponding entropic and enthalpic components. The entropically stabilized hydrophobic interaction between ALA and PHE in bulk water is enthalpically dominated upon confinement depending on the relative orientations between the side chains. In the case of SER-ASN, hydrogen bonded configurations that are similar in bulk water are thermodynamically distinct in a cylindrical pore, thus making rotamer distributions different from those in the bulk. Remarkably, salt bridge formation between LYS-GLU is stabilized by entropy in contrast to the bulk. Implications of our findings for confinement-induced alterations in protein stability are briefly outlined.


Combination therapy of radiofrequency ablation and transarterial chemoembolization in recurrent hepatocellular carcinoma after hepatectomy compared with single treatment.
To assess the efficacy and safety of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) in recurrent hepatocellular carcinoma (HCC) after hepatectomy and to compare its outcome with a single modality. We retrospectively studied 103 patients with recurrent HCCs after hepatectomy who were excluded from repeat hepatectomy. Of them, 81 patients were male and 22 were female (mean age 55.8 +/- 10.7 years; range, 30-80 years). According to treatment modality, these patients were divided into three groups: RFA was used as the sole first-line anticancer treatment in 37 patients (RFA group); TACE was used as the sole first-line anticancer treatment in 35 patients (TACE group). RFA followed by TACE was performed in 31 patients (combination group). There was no significant difference in clinical material between the three groups. Indices including treatment success rate, intrahepatic recurrence rate and survival were obtained for analysis and comparison. The treatment success rate of the combination group was significantly higher than that of the TACE group (93.5 vs. 68.6%, P = 0.011). The intrahepatic recurrence rate of the combination group was significantly lower than that of the TACE group (20.7 vs 57.1%, P = 0.002) and the RFA group (20.7 vs 43.2%, P = 0.036). The overall 1-, 3- and 5-year survival rates were 73.9, 51.1 and 28.0% respectively in the RFA group; 65.8, 38.9 and 19.5% respectively in the TACE group; and 88.5, 64.6 and 44.3% respectively in the combination group. There was a significant difference in survival between the combination group and the TACE group (P = 0.028). RFA combined with TACE was more effective in treating recurrent HCC after hepatectomy compared to single RFA or TACE treatment. This combination therapy can thus be a valuable choice of treatment for recurrent HCC.


Screening of Anti-Biofilm Compounds from Marine-Derived Fungi and the Effects of Secalonic Acid D on Staphylococcus aureus Biofilm.
Biofilm formation of Staphylococcus aureus is one of its mechanisms of drug resistance. Antibiofilm screening of 106 compounds from marine-derived fungi displayed that 12 compounds inhibited S. aureus biofilm formation by >50% at the concentration of 100 μg/ml, and only secalonic acid D (SAD) and B inhibited by >90% at 6.25 μg/ml without inhibiting cell growth after 24-h incubation. Meanwhile, it was found that the double bond between C-1 and C-10 of citrinin derivatives and the C-C connection position of two chromone monomers may be important for their anti-biofilm activities. Moreover, SAD slightly facilitated biofilm eradication and influenced its architecture. Furthermore, SAD slowed the cell growth rate in the preceding 18-h incubation and differentially regulated transcriptional expression of several genes, such as agr, isaA, icaA, and icaD, associated with biofilm formation in planktonic and biofilm cells, which may be the reason for the anti-biofilm activity of SAD. Finally, SAD acted synergistically against S. aureus growth and biofilm formation with other antibiotics. These findings indicated that various natural products from marine-derived fungi, such as SAD, could be used as a potential biofilm inhibitor against S. aureus.


Listeners' effects on autobiographical memory for recent events.
The current study tested the effects of attentive versus distracted listening on both speakers and listeners in recall of an autobiographical memory. Participants included 128 pairs of friends who spoke with each other over a video call about recent negative experience that one of them had. Participants were randomly assigned to be speakers or listeners, and listeners were randomly assigned to an attentive and a distracted condition. Memory narratives were coded for factual and interpretive content. Participants returned approximately 4 weeks later, when both speaker and listener separately reported their memories of the prior conversation. Attentive listening was linked both to greater recall by the speaker at time 1 and greater listener recall at time 2, but not to speaker's recall at time 2. Results show the effects of listener contributions to recall in the moment but raise questions as to whether they persist beyond the conversation in many scenarios.


Abnormal Static and Dynamic Functional Connectivity in Left and Right Temporal Lobe Epilepsy.
Temporal lobe epilepsy (TLE) can be conceptualized as a network disease. However, the network characteristics in lateralization remain controversial. In this study, resting-state functional MRI scans were acquired from 53 TLE patients [22 with left-side TLE (LTLE) and 31 with right-side TLE (RTLE)] and 37 matched healthy controls. We focused on the characteristics of static and dynamic functional connectivity, including static connectivity patterns and topological properties, as well as temporal properties of the dynamic connectivity state and the variability of the dynamic connectivity and network topological organization. Correlation analyses were conducted between abnormal static and dynamic properties and cognitive performances. The static functional connectivity analysis presented a significantly decreased cortical-cortical connectivity pattern and increased subcortical-cortical connectivity pattern in RTLE. The global-level network in RTLE showed a significant decrease in global efficiency. The dynamic functional connectivity analysis revealed that RTLE patients exhibited aberrant connectivity states, as well as increased variability in the subcortical-cortical connectivity. The global-level network in RTLE revealed increased variance in global efficiency and local efficiency. The static or dynamic functional connectivity in LTLE did not show any significant abnormalities. The altered dynamic properties were associated with worsening cognitive performance in language and conceptual thinking by the TLE patients. Our findings demonstrated the presence of abnormalities in the static and dynamic functional connectivity of TLE patients. RTLE patients exhibited more pronounced aberrant connectivity patterns and topological properties, which might represent a mechanism for reconfiguration of brain networks in RTLE patients. These observations extended our understanding of the pathophysiological network mechanisms of TLE.


2-amino-4H-3,1-benzoxazin-4-ones as inhibitors of C1r serine protease.
A series of 2-amino-4H-3,1-benzoxazin-4-ones have been synthesized and evaluated as inhibitors of the complement enzyme C1r. C1r is a serine protease at the beginning of the complement cascade, and complement activation by beta-amyloid may represent a major contributing pathway to the neuropathology of Alzheimer's disease. Compounds such as 7-chloro-2-[(2-iodophenyl)-amino]benz[d][1,3]oxazin-4-one (32) and 7-methyl-2-[(2-iodophenyl)amino]benz[d][1,3]oxazin-4-one (37) show improved potency compared to the reference compound FUT-175. Many of these active compounds also possess increased selectivity for C1r compared to trypsin and enhanced hydrolytic stability relative to 2-(2-iodophenyl)-4H-3,1-benzoxazin-4-one (1).


Cardiolipin dynamics and binding to conserved residues in the mitochondrial ADP/ATP carrier.
Cardiolipin in eukaryotes is found in the mitochondrial inner membrane, where it interacts with membrane proteins and, although not essential, is necessary for the optimal activity of a number of proteins. One of them is the mitochondrial ADP/ATP carrier, which imports ADP into the mitochondrion and exports ATP. In the crystal structures, cardiolipin is bound to three equivalent sites of the ADP/ATP carrier, but its role is unresolved. Conservation of residues at these cardiolipin binding sites across other members of the mitochondrial carrier superfamily indicates cardiolipin binding is likely to be important for the function of all mitochondrial carriers. Multiscale simulations were performed in a cardiolipin-containing membrane to investigate the dynamics of cardiolipin around the yeast and bovine ADP/ATP carriers in a lipid bilayer and the properties of the cardiolipin-binding sites. In coarse-grain simulations, cardiolipin molecules bound to the carriers for longer periods of time than phosphatidylcholine and phosphatidylethanolamine lipids-with timescales in the tens of microseconds. Three long-lived cardiolipin binding sites overlapped with those in the crystal structures of the carriers. Other shorter-lived cardiolipin interaction sites were identified in both membrane leaflets. However, the timescales of the interactions were of the same order as phosphatidylcholine and phosphatidylethanolamine, suggesting that these sites are not specific for cardiolipin binding. The calculation of lipid binding times and the overlap of the cardiolipin binding sites between the structures and simulations demonstrate the potential of multiscale simulations to investigate the dynamics and behavior of lipids interacting with membrane proteins.


Magnetooptical modulator with crystal in a separated auxiliary field.
The classical magnetooptic modulator based on Faraday rotation is improved by using the separated auxiliary field instead of a perpendicular one. Theoretical analysis indicates an improvement in some modulator parameters. Experiments have confirmed growth of the modulation depth and reduction in nonlinear characteristics of the modulator.


Newborn screening for congenital adrenal hyperplasia in New Zealand, 1994-2013.
The objective of the study was to evaluate the efficacy of national newborn screening for severe congenital adrenal hyperplasia (CAH) in New Zealand over the past 20 years. Newborn screening for CAH is performed through the estimation of 17-hydroxyprogesterone by a Delfia immunoassay. CAH cases diagnosed in the newborn period from 1994 to 2013 were identified from Newborn Metabolic Screening Programme records. Between 1994 and 2013, 44 neonates (28 females, 16 males) were diagnosed with CAH, giving an incidence of 1:26 727. Almost half (n = 21) of the newborns with CAH were detected solely via screening (not clinically suspected), including 21% of all affected females. Among the group solely ascertained by screening, 17-hydroxyprogesterone sampling occurred at a mean age of 3.3 days (range 2-8 d), the duration from sampling to notification was 5.2 days (0-12 d), and treatment was initiated at 12.0 days (6-122 d). Vomiting was present in 14% of those ascertained by screening, but none had hypotension or collapse at diagnosis. Increasing age at treatment was correlated with a progressive decrease in serum sodium (r = -0.56; P < .0001) and an increase in serum potassium concentrations (r = 0.38; P = .017). Compared with newborns diagnosed by screening alone, those clinically diagnosed were predominantly female (96% vs 29%; P < .0001), notification occurred earlier (4.8 vs 8.5 d; P = .002), and had higher serum sodium (136.8 vs 130.8 mmol/L; P < .0001) and lower serum potassium (5.3 vs 6.0 mmol/L; P = .011) concentrations. Screening alone accounted for nearly 50% cases of CAH detected in the newborn period, including a fifth of affected females, indicating that clinical diagnosis is unreliable in both genders. Symptoms were mild at diagnosis and there were no adrenal crises. This study confirms the benefits of newborn CAH screening.


On the nature of DNA-duplex stability.
The unwinding free energy of 128 DNA octamers was correlated with the sum of interaction energies among DNA bases and their solvation energies. The former energies were determined by using the recently developed density functional theory procedure augmented by London dispersion energy (RI-DFT-D) that provides accurate hydrogen-bonding and stacking energies highly comparable with CCSD(T)/complete basis set limit benchmark data. Efficient tight-binding DFT covering dispersion energy was also used and yielded satisfactory results. The latter method can be used for extended systems. The solvation energy was determined by using a C-PCM continuum solvent at HF level calculations. Various models were adopted to correlate theoretical energies with experimental unwinding free energies. Unless all energy components (hydrogen-bonding, intra- and interstrand-stacking, and solvation energies) were included and weighted individually, no satisfactory correlation resulted. The most advanced model yielded very close correlation (RMSE=0.32 kcal mol(-1)) fully comparable with the entirely empirical correlation introduced in the original paper. Analysis of the theoretical results shows the importance of inter- and intramolecular stacking energies, and especially the latter term plays a key role in determining DNA-duplex stabilization.


Enigmatic pain referred to the teeth and jaws.
A number of obscure syndromes can mimic dental or jaw pain in the absence of pathosis within these structures. This enigmatic dental pain includes conditions such as pretrigeminal neuralgia, complex regional pain syndrome, temporal tendinitis, and carotodynia. Each of these syndromes is described through a pertinent case report to illustrate appropriate diagnosis and treatment.


[Postmastectomy breast reconstruction. 10-year experience in the hospital of Santarém].
The authors describe ten years of experience in breast reconstruction in the Department of Plastic and Reconstructive Surgery in the District Hospital of Santarém--Portugal. Ninety-nine patients were treated with 106 reconstructions, most of these were immediate and some were delayed. The authors were interested in providing an adequate volume, but also into obtaining an acceptable aesthetic result. This contributes considerably to the psychological recovery of the patients.


[Differential aspects of treatment dropout risk in cocaine dependent patients with and without personality disorders].
The aim of this study was to examine the link between psychosocial adjustment, impulsivity and comorbid Axis II psychopathology, and the risk of treatment dropout in cocaine dependent patients. The sample consisted of 95 cocaine dependent participants, 53.7% of whom had been diagnosed with Axis II personality disorders. We utilised a descriptive methodology, which allowed us to examine correlations between the different variables, group differences in these variables, and their ability to predict different dimensions associated with the risk of dropout. Results show that the risk of dropout during the first two months of treatment is not associated with the existence of comorbid personality disorders. With regard to the cognitive profiles of personality disorders, we show that the antisocial profile is associated with higher risk of dropout. The profile of patients at higher risk of treatment dropout is characterised by lower levels of perceived quality of life and elevated levels of impulsivity, especially the experience of strong impulses under positive affect. Therefore, the presence of psychological dimensions tightly associated with emotions, affects and subjective feelings are the more relevant to estimate the risk of treatment dropout in cocaine dependent patients. This study stresses the variables that need to be specifically addressed during early phases of cocaine addiction treatment, since they are associated with higher risk of treatment dropout.


Activity and tissue-specific expression of lipases and tumor-necrosis factor alpha in lean and obese cats.
Post-heparin plasma activity of lipoprotein lipase (LPL) and hepatic lipase (HL), and fat and muscle activity of LPL were measured in neutered lean and obese cats. Lipoprotein lipase, hormone-sensitive lipase (HSL), and tumor necrosis factor a (TNF) mRNA were measured in muscle and fat tissue with real-time PCR using primers for feline LPL, HSL, and TNF. Lipoprotein lipase plasma and fat activity and fat mRNA levels were significantly lower (50, 80, and 50%, respectively) in obese cats than lean cats, whereas the muscle/fat ratio of LPL was significantly higher in obese compared to lean cats. The activity of HL was not different between the groups. Hormone-sensitive lipase mRNA levels were significantly higher in obese than lean cats. The level of fat TNF also was significantly higher in obese cats than in lean cats, whereas the level in muscle was not different. The lower LPL activity and mRNA expression in fat and the higher LPL and HSL mRNA expression in muscle in obese cats compared to lean cats expectedly favor a redistribution of fatty acids from fat to muscle tissue where they can be deposited or used for energy in times of need. Tumor necrosis factor alpha may regulate this repartitioning process through suppression of adipocyte LPL.


Histopathological findings for prediction of liver cirrhosis and survival in biliary atresia patients after Kasai procedure.
Without early recognition and Kasai procedure, biliary atresia (BA) results in liver cirrhosis and leads to either transplantation or death at a young age. We aimed to characterize the liver histopathological findings for prediction of cirrhosis and survival in BA patients after Kasai surgery. We retrospectively reviewed all histopathological results for BA patients who underwent liver biopsy during Kasai surgery from August 2012 to December 2018 in Dr. Sardjito Hospital, Yogyakarta, Indonesia. Fifty infants with BA were ascertained in our study, of whom 27 were males and 23 were females. The median age of Kasai procedure was 102.5 days (interquartile range (IQR), 75.75-142.25 days). There were 33 (66%) and 17 (34%) BA patients with and without liver cirrhosis, respectively, while the overall survival was 52%. The patients with a severe bile duct proliferation, severe cholestasis, and severe portal inflammation have a higher risk by 27-, 22-, and 19.3-fold, respectively, to develop liver cirrhosis compared with patients with a moderate/mild bile duct proliferation, moderate/mild/without cholestasis, and moderate/mild portal inflammation, respectively (p = 3.6 × 10- 6, 5.6 × 10- 4, and 1.6 × 10- 3, respectively), while the giant cell transformation was not associate with the development of liver cirrhosis (p = 0.77). The bile duct proliferation was strongly correlated with cholestasis and portal inflammation (p = 7.3 × 10- 5 and 2 × 10- 4, respectively), and cholestasis was also significantly correlated with portal inflammation (p = 0.016). Interestingly, the age at Kasai procedure was strongly associated with the development of liver cirrhosis (p = 0.02), but not with the patients' survival (p = 0.33), while the degree of fibrosis and cholestasis were significantly correlated with the patients' survival, with HR of 3.9 (95% CI = 1.7-9.0; p = 0.017) and 3.1 (95% CI = 1.4-7.0; p = 0.016), respectively. Histopathological findings of bile duct proliferation, cholestasis, and portal inflammation can predict the liver cirrhosis development in patients with BA. Furthermore, degree of fibrosis and cholestasis affect the patients' survival following the Kasai operation.


The Relationship Between FoxP3 and SOCs3 Gene Expressions and Disease Activity in Rheumatoid Arthritis.
Immune dysregulation plays an important role in the pathogenesis of rheumatoid arthritis (RA). The CD4+CD25 high FoxP3+ subset of regulatory T cells plays an essential role in preventing autoimmunity and maintaining immune homeostasis. Negative regulation of JAK/STAT signaling is controlled by Suppressor of Cytokine Signaling (SOCs3) proteins. SOCs is produced at lower levels in RA. Our aim was to evaluate the expressional dysregulation of SOCs3 and FoxP3 genes in RA patients in relation to disease activity. We have recruited 90 patients with RA and 60 healthy controls in case control study. Whole blood samples were collected from RA patients and healthy subjects. The measurement of FoxP3 and SOCs3 gene expression was performed by real-time PCR (qPCR). Patients with RA had significantly decreased expression levels of FoxP3 and SOCs3 genes in comparison with controls (P<0.001), in addition to the insignificance correlation of both genes with disease activity in RA patients. FoxP3 and SOCs3 genes showed significant defects in rheumatoid arthritis patients with no significant difference in disease activity.


A Diagnostic Score (DS) in the Difficult Diagnosis of Non-specific Abdominal Pain (NSAP).
The diagnostic scores (DSs) for patients with non-specific abdominal pain (NSAP) have been rarely evaluated. In the NSAP study group there were 614 patients (268 females and 346 males) versus 719 patients in the non-NSAP group including 368 females and 351 males. The clinical symptoms (n=22), signs and tests (n=14) and laboratory analyses (n=3) were recorded in each patient. Meta-analytical techniques were used to detect the summary sensitivity (Se) and specificity (Sp) estimates for each data set (symptoms, signs and tests as well as DS models). In receiver operating characteristic (ROC) analysis, the area under curve (AUC) values for i) symptoms ii) signs and tests and iii) DS were as following: i) AUC=0.542 (95% CI=0.512-0.572); ii) AUC=0.625 (95% CI=0.550-0.700), and iii) AUC=0.874 (95% CI=0.850-0.898). The differences between these AUC values are as following: between i and ii, p=0.097; between i and iii, p<0.0001 and between ii and iii, p<0.0001. This is the first study to provide evidence that DS may help in the difficult diagnosis of NSAP.


Patient dose and image quality in five standard x-ray examinations.
Patient doses and image quality in five standard x-ray examination projections (22-36 measurements per each projection) have been measured, using homogeneous phantoms. The means and range of variation for the entrance skin air kerma values were: abdomen AP 5.2 mGy (1.1-21 mGy), chest PA 0.27 mGy (0.035-0.84 mGy), lumbar spine AP 8.4 mGy (2.9-28 mGy), skull LAT 3.1 mGy (1.1-7.7 mGy), and thoracic spine AP 7.9 mGy (1.3-22 mGy). Considerable variation was found in image quality parameters: film optical densities, image contrasts, and resolutions as well as in exposure values, tube voltages, exposure times, and in half-value thicknesses. The study indicated the need to standardize medical x-ray examination techniques in different x-ray departments. The measuring method can be used for comparing the patient dose and image quality of an individual x-ray unit to the doses and image quality in general use. The results can be used as the reference values for quality control of x-ray equipment.


Changes in the hemagglutinin molecule of influenza type A (H3N2) virus associated with increased virulence for mice.
The H3N2 influenza virus A/Philippines/82 (Phil82) and its bovine serum-resistant mutant, Phil82/BS, were used to investigate factors that influence virulence of influenza virus for mice. Phil82/BS, which lacks the high-mannose oligosaccharide at residue 165 of the hemagglutinin (HA) molecule, was found to replicate to a much higher titer in mouse lung than the parent Phil82, and had acquired lethality for mice. Further adaptation of Phil82/BS by sequential lung passage in mice yielded a strain of greater virulence, Phil82/BS/ML 10, in which a change at residue 246 of HA resulted in loss of a second potential glycosylation site. Phil82 is highly sensitive to neutralization in vitro by murine serum- and lung-associated mannose-binding lectins (collectins). Characterization of the two mutant viruses indicated that resistance to murine collectins can account for the enhanced virulence of Phil82/BS but not for the further increase in virulence of Phil82/BS/ML10. Evidence is presented that residue 246 is not in fact glycosylated in Phil82/BS HA, nor presumably in the parent Phil82 virus. The HA molecule of Phil82/BS/ML10 displayed functional differences from Phil82/BS, including a change in the optimum pH of fusion and a minor change in receptor-binding specificity, which may allow improved efficiency of replication in the mouse lung.


Free-Sustaining Three-Dimensional S235 Steel-Based Porous Electrocatalyst for Highly Efficient and Durable Oxygen Evolution.
A novel oxygen evolution reaction (OER) catalyst (3 D S235-P steel) based on a steel S235 substrate was successfully prepared by facile one-step surface modification. The standard carbon-manganese steel was phosphorized superficially, which led to the formation of a unique 3 D interconnected nanoporous surface with a high specific area that facilitated the electrocatalytically initiated oxygen evolution reaction. The prepared 3 D S235-P steel exhibited enhanced electrocatalytic OER activities in the alkaline regime, as confirmed by a low overpotential (326 mV at a 10 mA cm-2 ) and a small Tafel slope of 68.7 mV dec-1 . Moreover, the catalyst was found to be stable under long-term usage conditions, functioning as an oxygen-evolving electrode at pH 13, as evidenced by the sufficient charge-to-oxygen conversion rate (faradaic efficiency: 82.11 and 88.34 % at 10 and 5 mA cm-2 , respectively). In addition, it turned out that the chosen surface modification delivered steel S235 as an OER electrocatalyst that was stable under neutral pH conditions. Our investigation revealed that the high catalytic activities likely stemmed from the generated Fe/(Mn) hydroxide/oxohydroxides generated during the OER process. Phosphorization treatment therefore not only is an efficient way to optimize the electrocatalytic performance of standard carbon-manganese steel but also enables for the development of low-costing and abundant steels in the field of energy conversion.


The role of microglia in multiple sclerosis.
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). Microglia are the resident innate immune cells in the CNS; they play an important role in the processes of demyelination and remyelination in MS. Microglia can function as antigen-presenting cells and phagocytes. In the past, microglia were considered to be the same cell type as macrophages, and researchers have different opinions about the role of microglia in MS. This review focuses on the original classification of microglia and their role in the pathogenesis of MS. Moreover, we present a hypothetical model for the role of microglia in the pathogenesis of MS based on recent findings.


Mechatronic Design and Experimental Research of an Automated Photogrammetry-Based Human Body Scanner.
The article concerns the mechatronic design and experimental investigations of the HUBO automated human body scanning system. Functional problems that should be solved by using the developed scanning system are defined. These include reducing the number of sensors used while eliminating the need to rotate a human and ensuring the automation of the scanning process. Research problems that should be the subject of experimental research are defined. The current state of the art in the field of systems and techniques for scanning the human figure is described. The functional and technical assumptions for the HUBO scanning system are formulated. The mechanical design of the scanner, the hardware and information system architectures as well as the user's mobile application are presented. The method of operation of the scanning system and its innovative features are discussed. It is demonstrated that the developed solution of the scanning system allows the identified problems to be overcome. The methodology of the experimental research of the scanning system based on the photogrammetry technique is described. The results of laboratory studies with the use of dummies and experimental research with human participation are presented. The scope of the research carried out allows answers to the identified research problems related to the scanning of the human figure using the photogrammetry technique to be obtained. As part of laboratory tests using a measuring dummy, a mean error of 0.65 mm and standard deviation of the mean of 0.65 mm were obtained for the best scanner configuration. Research with human participation was carried out for the scanner version, in which the scanning time was 30 s, with the possibility of its reduction to 15 s. The results of studies using realistic dummies and with human participation were compared using the root mean square error parameter (RMSE) provided by the AliceVision framework, which was available for all analyzed objects. As a result, it was observed that these results are comparable, i.e., the RMSE parameter is equal to about 1 px.


Energy-Efficient Nitrogen Reduction to Ammonia at Low Overpotential in Aqueous Electrolyte under Ambient Conditions.
The electrochemical nitrogen reduction reaction (NRR) under ambient conditions is a promising alternative to the traditional energy-intensive Haber-Bosch process to produce NH3 . The challenge is to achieve a sufficient energy efficiency, yield rate, and selectivity to make the process practical. Here, we demonstrate that Ru nanoparticles (NPs) enable NRR in 0.01 m HCl aqueous solution at very high energy efficiency, that is, very low overpotentials. Remarkably, the NRR occurs at a potential close to or even above the H+ /H2 reversible potential, significantly enhancing the NRR selectivity versus the production of H2 . NH3 yield rates as high as ≈5.5 mg h-1 m-2 at 20 °C and 21.4 mg h-1 m-2 at 60 °C were achieved at a redox potential (E) of -100 mV versus the reversible hydrogen electrode (RHE), whereas a highest Faradaic efficiency (FE) of ≈5.4 % is achievable at E=+10 mV vs. RHE. This work demonstrates the potential use of Ru NPs as an efficient catalyst for NRR at ambient conditions. This ability to catalyze NRR at potentials near or above RHE is imperative in improving the NRR selectivity towards a practical process as well as rendering the H2 viable as byproduct. Density functional theory calculations of the mechanism suggest that the efficient NRR process occurring on these predominantly Ru (0 0 1) surfaces is catalyzed by a dissociative mechanism.