bluuebunny/crossref_metadata_2025 huggingface dataset:
Sniff nasal inspiratory pressure in the longitudinal assessment of young Duchenne muscular dystrophy children
Authors: Nève Véronique , Cuisset Jean-Marie , Edmé Jean-Louis , Carpentier Alain , Howsam Mike , Leclerc Olivier , Matran Régis
Published: December 2012

Traditional measures of respiratory function in children with Duchenne muscular dystrophy (DMD) are based on maximal inspiratory pressure (PImax) and vital capacity (VC). Sniff nasal inspiratory pressure (SNIP) measurements are easily performed by young children with neuromuscular disorders. The clinical value of SNIP in the longitudinal assessment of respiratory weakness remains to be assessed. The objective of the present study was to assess longitudinally the changes in SNIP,PImaxand VC with age in DMD children. We hypothesised that their longitudinal assessment would show an earlier decline in SNIP than VC.

A 3-year, prospective follow-up, at 6-month intervals of, 33 steroid-naïve, 5–20-year-old DMD patients was analysed using a linear mixed model.

SNIP measurements were reliable (within-session coefficient of variation 8%). SNIP and VC increased until 10.5 and 12.5 years of age, respectively, and declined thereafter, whilePImaxdid not change with age.

SNIP was an earlier marker of decline in respiratory muscle strength (at 10.5 years) than VC (at 12.5 years) in young DMD patients. SNIP longitudinal assessment is useful in the detection of inspiratory strength decline in young DMD patients when VC values remain within normal values and as an outcome measure in clinical trials for emerging therapeutics in young DMD patients from the age of 5 years.
Effects of obstructive sleep apnoea on heart rhythm
Authors: Rossi Valentina A. , Stradling John R. , Kohler Malcolm
Published: December 2012

Symptomatic obstructive sleep apnoea (OSA) has been proven to be a risk factor for hypertension and vascular dysfunction, and has been proposed to be causally related with cardiac arrhythmias and sudden cardiac death.

Searches of bibliographical databases revealed that several mechanisms seem to underpin the association between OSA and cardiac arrhythmias: intermittent hypoxia associated with autonomic nervous system activation and increased oxidative stress, which may lead to cardiac cellular damage and alteration in myocardial excitability; recurrent arousals, resulting in sympathetic activation and coronary vasoconstriction; and increased negative intrathoracic pressure which may mechanically stretch the myocardial walls and, thus, promote acute changes in myocardial excitability as well as structural remodelling of the myocardium.

Findings from cross-sectional studies suggest a high prevalence of cardiac arrhythmias in patients with OSA and a high prevalence of OSA in those with cardiac arrhythmias. Preliminary evidence from uncontrolled interventional studies suggests that treatment of OSA may prevent cardiac arrhythmias.

In conclusion, there is preliminary evidence that OSA is associated with the development of cardiac arrhythmias. Data from randomised controlled studies are needed to definitively clarify the role of OSA in arrhythmogenesis.
Pulmonary function and sputum characteristics predict computed tomography phenotype and severity of COPD
Authors: Camiciottoli Gianna , Bigazzi Francesca , Paoletti Matteo , Cestelli Lucia , Lavorini Federico , Pistolesi Massimo
Published: December 2012

Airway obstruction and parenchymal destruction underlie phenotype and severity in chronic obstructive pulmonary disease (COPD). We aimed to predict, by clinical and pulmonary function data, the predominant type and severity of pathological changes quantitatively assessed by computed tomography (CT).

Airway wall thickness (AWT-Pi10) and percentage of lung area with X-ray attenuation values <-950 HU (%LAA-950) were measured in 100 (learning set) out of 473 COPD outpatients undergoing clinical and functional evaluation. Original CT measurements were translated by principal component analysis onto a plane with the novel coordinates CT1 and CT2, depending on the difference (prevalent mechanism of airflow limitation) and on the sum (severity) of AWT-Pi10 and %LAA-950, respectively. CT1 and CT2, estimated in the learning set by cross-validated models of clinical and functional variables, were used to classify 373 patients in the testing set.

A model based on diffusing capacity of the lung for carbon monoxide, total lung capacity and purulent sputum predicted CT1 (r = 0.64; p<0.01). A model based on forced expiratory volume in 1 s/vital capacity, functional residual capacity and purulent sputum predicted CT2 (r = 0.77; p<0.01). Classification of patients in the testing set obtained by model-predicted CT1 and CT2 reflected, according to correlations with clinical and functional variables, both COPD phenotype and severity.

Multivariate models based on pulmonary function variables and sputum purulence classify patients according to overall severity and predominant phenotype of COPD as assessed quantitatively by CT.
Opioids for chronic refractory breathlessness: patient predictors of beneficial response
Authors: Johnson Miriam J. , Bland J. Martin , Oxberry Stephen G. , Abernethy Amy P. , Currow David C.
Published: December 2012

Chronic refractory breathlessness is common and distressing in advanced disease. Despite level I evidence to support the use of opioids for this symptom, not all patients benefit. This study aimed to discover which patient characteristics predict those most likely to gain improvement in breathlessness.

This is an international, multicentre, retrospective analysis of 213 individual pooled datasets from four clinical trials of an opioid for chronic refractory breathlessness. “Response to opioid” was defined as 1) an absolute value of ≥10 mm improvement on the visual analogue scale (VAS) and 2) a relative value of ≥10% improvement from baseline VAS. We investigated baseline predictors using logistic regression.

In the final model, higher baseline breathlessness intensity scores strongly predicted absolute and relative response (p<0.001). Younger age also predicted relative response (p = 0.025); functional status and dominant cause of breathlessness did not. Some evidence supported the descriptor “not enough air”, but was not statistically significant (p = 0.052).

A therapeutic trial of opioids is appropriate, irrespective of the cause of the breathlessness or functional status. Younger people or those with worse breathlessness are more likely to benefit. Opioids have a role in the management of chronic refractory breathlessness, but net benefit for individuals must be optimised.
Serotypes associated with the development of pneumococcal para-pneumonic effusion in adults
Authors: Bewick Thomas , Sheppard Carmen , Greenwood Sonia , Slack Mary , Trotter Caroline , George Robert , Lim Wei Shen
Published: December 2012

Serotypes 1, 3, 7F and 19A are implicated in childhood pneumococcal para-pneumonic effusion (PPE). It is not known whether the same is true for adult PPE.

A prospective cohort study was conducted over a 2-year period. Consecutive adults admitted with community-acquired pneumonia (CAP) were studied. Pneumococcal serotype was identified from urine samples using a multiplex immunoassay.

Of 920 patients recruited, 366 had pneumococcal CAP; 100 of these had PPE and a serotype was determined in 73 patients. Factors associated with PPE were age, pneumonia severity index score and serotype. Serotypes most associated with PPE were 1 (18 (45%) out of 40), 19A (9 (45%) out of 20) and 3 (8 (40%) out of 20). Serotypes common in childhood PPE were independently associated with adult PPE (adjusted OR 2.3; p = 0.003). Serotypes not included in the 7-valent pneumococcal conjugate vaccine (PCV) were more likely to be associated with PPE (OR 2.1; p = 0.024) compared with those in the vaccine. Serotypes included in PCV-13 were as likely to be associated with PPE as those that are not (OR 0.8; p = 0.301).

Serotypes 1, 3, 7F and 19A are independently associated with adult PPE, a similar finding to childhood PPE. Serotype replacement following pneumococcal vaccine implementation may influence the spectrum of clinical disease.
Xpert MTB/RIF for diagnosis of tuberculosis and drug-resistant tuberculosis: a cost and affordability analysis
Authors: Pantoja Andrea , Fitzpatrick Christopher , Vassall Anna , Weyer Karin , Floyd Katherine
Published: December 2012

Xpert MTB/RIF is a rapid test to diagnose tuberculosis (TB) and rifampicin-resistant TB. Cost and affordability will influence its uptake.

We assessed the cost, globally and in 36 high-burden countries, of two strategies for diagnosing TB and multidrug-resistant (MDR)-TB: Xpert with follow-on diagnostics, and conventional diagnostics. Costs were compared with funding available for TB care and control, and donor investments in HIV prevention and care.

Using Xpert to diagnose MDR-TB would cost US$70–90 million per year globally and be lower cost than conventional diagnostics globally and in all high-burden countries. Diagnosing TB in HIV-positive people using Xpert would also cost US$90–101 million per year and be lower cost than conventional diagnostics globally and in 33 out of 36 high-burden countries. Testing everyone with TB signs and symptoms would cost US$434–468 million per year globally, much more than conventional diagnostics. However, in European countries, Brazil and South Africa, the cost would represent <10% of TB funding.

Introducing Xpert to diagnose MDR-TB and to diagnose TB in HIV-positive people is warranted in many countries. Using it to test everyone with TB signs and symptoms is affordable in several middle-income countries, but financial viability in low-income countries requires large increases in TB funding and/or further price reductions.
COPD and air travel: does hypoxia-altitude simulation testing predict in-flight respiratory symptoms?
Authors: Edvardsen Anne , Ryg Morten , Akerø Aina , Christensen Carl Christian , Skjønsberg Ole H.
Published: December 2012

The reduced pressure in an aircraft cabin may cause significant hypoxaemia and respiratory symptoms in patients with chronic obstructive pulmonary disease (COPD). The current study evaluated whether there is a relationship between hypoxaemia obtained during hypoxia-altitude simulation testing (HAST), simulating an altitude of 2438 m, and the reporting of respiratory symptoms during air travel.

82 patients with moderate to very severe COPD answered an air travel questionnaire. Arterial oxygen tensions during HAST (PaO2HAST) in subjects with and without in-flight respiratory symptoms were compared. The same questionnaire was answered within 1 year after the HAST.

Mean±sdPaO2HASTwas 6.3±0.6 kPa and 62 (76%) of the patients hadPaO2HAST<6.6 kPa. 38 (46%) patients had experienced respiratory symptoms during air travel. There was no difference inPaO2HASTin those with and those without in-flight respiratory symptoms (6.3±0.7 kPaversus6.3±0.6 kPa, respectively; p=0.926). 54 (66%) patients travelled by air after the HAST, and patients equipped with supplemental oxygen (n=23, 43%) reported less respiratory symptoms when flying with than those without such treatment (four (17%)versus11 (48%) patients; p=0.039).

In conclusion, no difference inPaO2HASTwas found between COPD patients with and without respiratory symptoms during air travel.
Cluster analysis application identifies muscle characteristics of importance for beef tenderness
Authors: Chriki Sghaier , Gardner Graham E , Jurie Catherine , Picard Brigitte , Micol Didier , Brun Jean-Paul , Journaux Laurent , Hocquette Jean-Francois
Published: December 2012

Background

An important controversy in the relationship between beef tenderness and muscle characteristics including biochemical traits exists among meat researchers. The aim of this study is to explain variability in meat tenderness using muscle characteristics and biochemical traits available in the Integrated and Functional Biology of Beef (BIF-Beef) database. The BIF-Beef data warehouse contains characteristic measurements from animal, muscle, carcass, and meat quality derived from numerous experiments. We created three classes for tenderness (high, medium, and low) based on trained taste panel tenderness scores of all meat samples consumed (4,366 observations from 40 different experiments). For each tenderness class, the corresponding means for the mechanical characteristics, muscle fibre type, collagen content, and biochemical traits which may influence tenderness of the muscles were calculated.

Results

Our results indicated that lower shear force values were associated with more tender meat. In addition, muscles in the highest tenderness cluster had the lowest total and insoluble collagen contents, the highest mitochondrial enzyme activity (isocitrate dehydrogenase), the highest proportion of slow oxidative muscle fibres, the lowest proportion of fast-glycolytic muscle fibres, and the lowest average muscle fibre cross-sectional area. Results were confirmed by correlation analyses, and differences between muscle types in terms of biochemical characteristics and tenderness score were evidenced by Principal Component Analysis (PCA). When the cluster analysis was repeated using only muscle samples fromm. Longissimus thoracis(LT), the results were similar; only contrasting previous results by maintaining a relatively constant fibre-type composition between all three tenderness classes.

Conclusion

Our results show that increased meat tenderness is related to lower shear forces, lower insoluble collagen and total collagen content, lower cross-sectional area of fibres, and an overall fibre type composition displaying more oxidative fibres than glycolytic fibres.
RNAmap2D – calculation, visualization and analysis of contact and distance maps for RNA and protein-RNA complex structures
Authors: Pietal Michal J , Szostak Natalia , Rother Kristian M , Bujnicki Janusz M
Published: December 2012

Background

The structures of biological macromolecules provide a framework for studying their biological functions. Three-dimensional structures of proteins, nucleic acids, or their complexes, are difficult to visualize in detail on flat surfaces, and algorithms for their spatial superposition and comparison are computationally costly. Molecular structures, however, can be represented as 2D maps of interactions between the individual residues, which are easier to visualize and compare, and which can be reconverted to 3D structures with reasonable precision. There are many visualization tools for maps of protein structures, but few for nucleic acids.

Results

We developed RNAmap2D, a platform-independent software tool for calculation, visualization and analysis of contact and distance maps for nucleic acid molecules and their complexes with proteins or ligands. The program addresses the problem of paucity of bioinformatics tools dedicated to analyzing RNA 2D maps, given the growing number of experimentally solved RNA structures in the Protein Data Bank (PDB) repository, as well as the growing number of tools for RNA 2D and 3D structure prediction. RNAmap2D allows for calculation and analysis of contacts and distances between various classes of atoms in nucleic acid, protein, and small ligand molecules. It also discriminates between different types of base pairing and stacking.

Conclusions

RNAmap2D is an easy to use method to visualize, analyze and compare structures of nucleic acid molecules and their complexes with other molecules, such as proteins or ligands and metal ions. Its special features make it a very useful tool for analysis of tertiary structures of RNAs. RNAmap2D for Windows/Linux/MacOSX is freely available for academic users at http://iimcb.genesilico.pl/rnamap2d.html
Abundance, distribution and potential impact of transposable elements in the genome of Mycosphaerella fijiensis
Authors: Santana Mateus F , Silva José CF , Batista Aline D , Ribeiro Lílian E , da Silva Gilvan F , de Araújo Elza F , de Queiroz Marisa V
Published: December 2012

Background

Mycosphaerella fijiensis is a ascomycete that causes Black Sigatoka in bananas. Recently, the M. fijiensis genome was sequenced. Repetitive sequences are ubiquitous components of fungal genomes. In most genomic analyses, repetitive sequences are associated with transposable elements (TEs). TEs are dispersed repetitive DNA sequences found in a host genome. These elements have the ability to move from one location to another within the genome, and their insertion can cause a wide spectrum of mutations in their hosts. Some of the deleterious effects of TEs may be due to ectopic recombination among TEs of the same family. In addition, some transposons are physically linked to genes and can control their expression. To prevent possible damage caused by the presence of TEs in the genome, some fungi possess TE-silencing mechanisms, such as RIP (Repeat Induced Point mutation). In this study, the abundance, distribution and potential impact of TEs in the genome of M. fijiensis were investigated.

Results

A total of 613 LTR-Gypsy and 27 LTR-Copia complete elements of the class I were detected. Among the class II elements, a total of 28 Mariner, five Mutator and one Harbinger complete elements were identified. The results of this study indicate that transposons were and are important ectopic recombination sites. A distribution analysis of a transposable element from each class of the M. fijiensis isolates revealed variable hybridization profiles, indicating the activity of these elements. Several genes encoding proteins involved in important metabolic pathways and with potential correlation to pathogenicity systems were identified upstream and downstream of transposable elements. A comparison of the sequences from different transposon groups suggested the action of the RIP silencing mechanism in the genome of this microorganism.

Conclusions

The analysis of TEs in M. fijiensis suggests that TEs play an important role in the evolution of this organism because the activity of these elements, as well as the rearrangements caused by ectopic recombination, can result in deletion, duplication, inversion and translocation. Some of these changes can potentially modify gene structure or expression and, thus, facilitate the emergence of new strains of this pathogen.
Clostridium difficile 027 infection in Central Italy
Authors: Di Bella Stefano , Paglia Maria Grazia , Johnson Emma , Petrosillo Nicola
Published: December 2012

Background

Clostridium difficile (CD) has increasingly become recognised as a significant international health burden, often associated with the healthcare environment. The upsurge in incidence of CD coincided with the emergence of a hypervirulent strain of CD characterized as 027.

In 2010, 8 cases of CD 027 infections were identified in Italy. Since then, no further reports have been published. We describe 10 new cases of CD 027 infection occurring in Italy.

Methods

Since December 2010, stool samples of patients with severe diarrhea and clinical suspicion of the presence of a hypervirulent strain, were tested for CD 027 by the Xpert C. difficile PCR assay (Cepheid, Sunnyvale, CA). Clinical, epidemiological and laboratory data were collected.

Results

From December 2010 to April 2012, 24 faecal samples from 19 patients who fit the above criteria were submitted to our laboratory. Samples were collected from 7 different hospitals.

Of these, 17 had a positive PCR for CD and 10 were the epidemic 027 strain (59%). All PCR positive samples had a positive EIA toxin A/B test. Nine of 10 patients were recently exposed to antimicrobials and were healthcare-associated, including 4 with a history of long term care facility (LTCF) admission; the remaining case was community-associated, namely the wife of a patient with hospital-acquired CD 027 infection. Five patients experienced at least one recurrence of CD associated diarrhea (CDAD) with a total of 12 relapsing episodes. Of these, two patients had 5 and 6 relapses respectively.

We compared the 10 patients with 027 CDAD versus the 7 patients with non-027 CDAD. None of the 7 patients with non-027 CDAD had a recent history of LTCF admission and no subsequent relapses were observed (p = 0.04).

Conclusions

Our study shows that CD 027 is emerging in healthcare facilities in Italy. Whilst nosocomial acquisition accounted for the majority of such cases, 4 patients had history of a recent stay in a LTCF. We highlight the substantial risks of this highly transmissible organism in such environments. Moreover, 50% of our patients with CDAD from the 027 strain had high relapse rates which may serve to further establish this strain within the Italian health and social care systems.
Determining adult type 2 diabetes-related health care needs in an indigenous population from rural Guatemala: a mixed-methods preliminary study
Authors: Chary Anita , Greiner Miranda , Bowers Cody , Rohloff Peter
Published: December 2012

Background

In Guatemala, diabetes is an emerging public health concern. Guatemala has one of the largest indigenous populations in Latin America, and this population frequently does not access the formal health care system. Therefore, knowledge about the emergence of diabetes in this population is limited.

Methods

Interview participants (n=23) were recruited from a convenience sample of indigenous adults with type 2 diabetes at one rural diabetes clinic in Guatemala. A structured interview was used to assess knowledge about diabetes and its complications; access to diabetes-related health care and treatment; dietary and lifestyle changes; and family and social supports for individuals living with diabetes. Interviews were supplemented with two group interviews with community leaders and health care providers. Thematic analysis was used to produce insights into diabetes knowledge, attitudes, and practices. In addition, a chart review of the clinic’s electronic medical record identified all adult patients (n=80) presenting in one calendar year for a first-time diabetic consultation. Sociodemographic and clinical variables were extracted and summarized from these records.

Results

Salient demographic factors in both the structured interview and chart review samples included low educational levels and high indigenous language preference. In the interview sample, major gaps in biomedical knowledge about diabetes included understanding the causes, chronicity, and long-term end-organ complications of diabetes. Medication costs, medical pluralism, and limited social supports for dietary and lifestyles changes were major practical barriers to disease management. Quantitative data from medical records review revealed high rates of poor glycemic control, overweight and obesity, and medication prescription.

Conclusions

This study provides a preliminary sketch of type 2 diabetes in an indigenous Guatemalan population. Combined qualitative and quantitative data point towards particular needs for implementation and future research, including the need to address gaps in diabetes knowledge, to improve social support systems, and to address the cost barriers associated with disease treatment.
Expression of a type B RIFIN in Plasmodium falciparum merozoites and gametes
Authors: Mwakalinga Steven B , Wang Christian W , Bengtsson Dominique C , Turner Louise , Dinko Bismarck , Lusingu John P , Arnot David E , Sutherland Colin J , Theander Thor G , Lavstsen Thomas
Published: December 2012

Background

The ability ofPlasmodium falciparumto undergo antigenic variation, by switching expression among protein variants encoded by multigene families, such asvar,rifandstevor, is key to the survival of this parasite in the human host. The RIFIN protein family can be divided into A and B types based on the presence or absence of a 25 amino acid motif in the semi-conserved domain. A particular type B RIFIN, PF13_0006, has previously been shown to be strongly transcribed in the asexual and sexual stages ofP. falciparum in vitro.

Methods

Antibodies to recombinant PF13_0006 RIFIN were used in immunofluorescence and confocal imaging of 3D7 parasites throughout the asexual reproduction and sexual development to examine the expression of PF13_0006. Furthermore, reactivity to recombinant PF13_0006 was measured in plasma samples collected from individuals from both East and West African endemic areas.

Results

The PF13_0006 RIFIN variant appeared expressed by both released merozoites and gametes after emergence. 7.4% and 12.1% of individuals from East and West African endemic areas, respectively, carry plasma antibodies that recognize recombinant PF13_0006, where the antibody responses were more common among older children.

Conclusions

The stage specificity of PF13_0006 suggests that the diversity of RIFIN variants has evolved to provide multiple specialized functions in different stages of the parasite life cycle. These data also suggest that RIFIN variants antigenically similar to PF13_0006 occur in African parasite populations.
Plasmodium vivax infection in Anajás, State of Pará: no differential resistance profile among Duffy-negative and Duffy-positive individuals
Authors: Carvalho Tarcisio AA , Queiroz Maíse G , Cardoso Greice L , Diniz Isabela G , Silva Aylla NLM , Pinto Ana YN , Guerreiro João F
Published: December 2012

Background

There is large body of evidence that states that invasion of Plasmodium vivax requires the Duffy antigen, but the universality of this specificity is certainly now under question with recent reports showing that in some parts of the world P. vivax infects and causes disease in Duffy-negative people. These findings reinforce the idea that this parasite is rapidly evolving, being able to use other receptors than Duffy to invade the erythrocytes, which may have an enormous impact in P. vivax current distribution. The presence of P. vivax infection in Duffy-negative individuals was investigated in a cross-sectional study conducted in Anajás, Archipelago of Marajó, State of Pará, which is an area of malaria transmission in the Brazilian Amazonia.

Methods

Duffy genotyping and Plasmodium species diagnostic assays were performed successfully in 678 individuals. An allele-specific primer polymerase chain reaction (PCR) technique was used for Duffy blood group genotyping. Identification of Plasmodium species was achieved by conventional blood smear light microscopy and a TaqMan-based real-time PCR method to detect mitochondrial genome of Plasmodium falciparum and P. vivax.

Results

Plasmodium spp. infection was detected in 137 samples (20.2%). Prevalence of each Plasmodium species was 13.9% P. vivax, 5.8% P. falciparum, and 0.6% P. vivax plus P. falciparum. Overall, 4.3% (29/678) were genotyped as Duffy-negative (FY*B

ES
/*B

ES
). Among Duffy-negative individuals 6.9% were P. vivax PCR positive and among Duffy-positive 14.2% were P. vivax PCR positive. Although lower, the risk of Duffy-negatives to experience a P. vivax blood stage infection was not significantly different to that of Duffy-positives. Furthermore, the genotypic and allelic frequencies of the Duffy blood group among P. vivax-infected patients and in the control group did not differ significantly, also suggesting no reduction in infection rates among the carriers of FY*B

ES
allele.

Conclusions

The data obtained in Anajás showed no differential resistance vivax malaria among Duffy-negative and Duffy-positive individuals. This result needs additional confirmation through a deeper evaluation in a larger sample of patients with P. vivax malaria and molecular parasite characterization. Nonetheless, this genetic profile of the parasite may be contributing to the high incidence of malaria in the municipality.
Absence of subtelomeric rearrangements in selected patients with mental retardation as assessed by multiprobe T FISH
Authors: dos Santos Suely Rodrigues , Freire-Maia Dértia Villalba
Published: December 2012

Background

Mental retardation (MR) is a heterogeneous condition that affects 2-3% of the general population and is a public health problem in developing countries. Chromosomal abnormalities are an important cause of MR and subtelomeric rearrangements (STR) have been reported in 4-35% of individuals with idiopathic MR or an unexplained developmental delay, depending on the screening tests and patient selection criteria used. Clinical checklists such as that suggested by de Vries et al. have been used to improve the predictive value of subtelomeric screening.

Findings

Fifteen patients (1–20 years old; five females and ten males) with moderate to severe MR from a genetics outpatient clinic of the Gaffrée and Guinle Teaching Hospital (HUGG) of the Federal University of Rio de Janeiro State (UNIRIO) were screened with Multiprobe T FISH after normal high resolution karyotyping. No subtelomeric rearrangements were detected even though the clinical score of the patients ranged from four to seven.

Conclusion

In developing countries, FISH-based techniques such as Multiprobe T FISH are still expensive. Although Multiprobe T FISH is a good tool for detecting STR, in this study it did not detect STR in patients with unexplained MR/developmental delay even though these patients had a marked chromosomal imbalance. Our findings also show that clinical scores are not reliable predictors of STR.
Falciform ligament abscess from left sided portal pyaemia following malignant obstructive cholangitis
Authors: Warren Leigh R , Chandrasegaram Manju D , Madigan Daniel J , Dolan Paul M , Neo Eu L , Worthley Christopher S
Published: December 2012

Abscess formation of the falciform ligament is incredibly rare and perplexing when encountered for the first time. It is reported to occur in the setting of cholecystitis and cholangitis, but the pathophysiology is poorly understood.

In this case report, we present a 73-year-old man with falciform ligament abscess following cholangitis from an obstructive ampullary carcinoma. The patient was referred to the Royal Adelaide Hospital from a country hospital, with progressive jaundice, anorexia and nausea. Prior to transfer, he deteriorated with cholangitis, dehydration and renal failure. On arrival, his abdomen was exquisitely tender along the course of the falciform ligament. His blood tests revealed an elevated white cell count of 14.9 x 103/μl, bilirubin of 291μmol/l and creatinine of 347 μmol/l. His CA 19-9 was markedly elevated at 35,000 kU/l. A non-contrast computed tomography (CT) demonstrated gross biliary dilatation and a collection tracking along the path of the falciform ligament to the umbilicus.

The patient was commenced on intravenous antibiotics and underwent an urgent endoscopic retrograde cholangiopancreatogram (ERCP) with sphincterotomy and biliary stent drainage. Cholangiogram revealed a grossly dilated biliary tree, with abrupt transition at the ampulla, which on biopsy confirmed an obstructing ampullary carcinoma. Following ERCP, his jaundice and abdominal tenderness resolved. He was optimized over 4 weeks for an elective pancreaticoduodenectomy.

At operation, we found abscess transformation of the falciform ligament. Copious amounts of pus and necrotic material was drained. Part of the round ligament was resected along the undersurface of the liver. Histology showed that there was prominent histiocytic inflammation with granular acellular eosinophilic components. The patient recovered slowly but uneventfully.

A contrast CT scan undertaken 2 weeks post-operatively (approximately 7 weeks after the initial CT) revealed left portal venous thrombosis, which was likely to be a delayed discovery and was managed conservatively.

We present this patient’s operative images and radiographic findings, which may explain the pathophysiology behind this rare complication. We hypothesize that cholangitis, with secondary portal pyaemia and tracking via the paraumbilical veins, can cause infectious seeding of the falciform ligament, with consequent abscess formation.
Narrowing down the targets for yield improvement in rice under normal and abiotic stress conditions via expression profiling of yield-related genes
Authors: Tripathi Amit K , Pareek Ashwani , Sopory Sudhir K , Singla-Pareek Sneh L
Published: December 2012

Background

Crop improvement targeting high yield and tolerance to environmental stresses has become the need of the hour. Yield improvement via breeding or gene pyramiding aiming comprehensive incorporation of the agronomically favored traits requires an in-depth understanding of the molecular basis of these traits. The present study describes expression profiling of yield-related genes in rice with respect to different developmental stages and various abiotic stress conditions.

Results

Our analysis indicates developmental regulation of the yield-related genes pertaining to the genetic reprogramming involved at the corresponding developmental stage. The gene expression data can be utilized to specifically select particular genes which can potentially function synergistically for enhancing the yield while maintaining the source-sink balance. Furthermore, to gain some insights into the molecular basis of yield penalty during various abiotic stresses, the expression of selected yield-related genes has also been analyzed by qRT-PCR under such stress conditions. Our analysis clearly showed a tight transcriptional regulation of a few of these yield-related genes by abiotic stresses. The stress-responsive expression patterns of these genes could explain some of the most important stress-related physiological manifestations such as reduced tillering, smaller panicles and early completion of the life cycle owing to reduced duration of vegetative and reproductive phases.

Conclusions

Development of high yielding rice varieties which maintain their yield even under stress conditions may be achieved by simultaneous genetic manipulation of certain combination of genes such as LRK1 and LOG, based on their function and expression profile obtained in the present study. Our study would aid in investigating in future, whether over-expressing or knocking down such yield-related genes can improve the grain yield potential in rice.
Abdominal obesity and prolonged prone positioning increase risk of developing sclerosing cholangitis in critically ill patients with influenza A-associated ARDS
Authors: Weig Thomas , Schubert Mirjam I , Gruener Norbert , Dolch Michael E , Frey Lorenz , Miller Jens , Johnson Thorsten , Irlbeck Michael
Published: December 2012

Background

Secondary sclerosing cholangitis is a severe disease of the biliary tract. Over the last decade, several cases of sclerosing cholangitis in critically ill patients (SC-CIP) were reported. Reports in the literature so far are characterized by a wide variety of underlying causes of critical illness, thereby hindering a risk-factor analysis. We report on a homogenous cohort of critically ill patients with influenza A (H1N1) pneumonia and severe acute respiratory distress syndrome (ARDS), of whom a subgroup developed sclerosing cholangitis, allowing for probing of risk factors associated with SC-CIP.

Methods

Twenty-one patients (5 female, 16 male, 46.3 ± 10.8 years) with severe ARDS due to H1N1 pneumonia were retrospectively divided into two groups, characterized by the presence (n = 5) and absence of SC-CIP (n = 16). A large array of clinical data, laboratory parameters, and multi-detector computed tomography-derived measures were compared.

Results

Both patient groups showed severe pulmonary impairment. Severity of disease on admission day and during the first 14 days of treatment showed no difference. The patients developing SC-CIP had a higher body mass index (BMI) (37.4 ± 6.0 kg/m2 vs. 29.3 ± 6.8 kg/m2; P = 0.029) and a higher volume of intraperitoneal fat (8273 ± 3659 cm3 vs. 5131 ± 2268 cm3; P = 0.033) and spent a longer cumulative period in the prone position during the first 14 days (165 ± 117 h vs. 78 ± 61 h; P = 0.038).

Conclusion

Our results suggest that obesity, intraperitoneal fat volume, and a longer cumulative duration spent in the prone position may put patients with ARDS at risk of developing SC-CIP. These results lead us to propose that the prone position should be carefully deployed, particularly in abdominally obese patients, and that frequent checks be made for early hepatic dysfunction.
HLA typing from RNA-Seq sequence reads
Authors: Boegel Sebastian , Löwer Martin , Schäfer Michael , Bukur Thomas , de Graaf Jos , Boisguérin Valesca , Türeci Özlem , Diken Mustafa , Castle John C , Sahin Ugur
Published: December 2012

We present a method, seq2HLA, for obtaining an individual's human leukocyte antigen (HLA) class I and II type and expression using standard next generation sequencing RNA-Seq data. RNA-Seq reads are mapped against a reference database of HLA alleles, and HLA type, confidence score and locus-specific expression level are determined. We successfully applied seq2HLA to 50 individuals included in the HapMap project, yielding 100% specificity and 94% sensitivity at a P-value of 0.1 for two-digit HLA types. We determined HLA type and expression for previously un-typed Illumina Body Map tissues and a cohort of Korean patients with lung cancer. Because the algorithm uses standard RNA-Seq reads and requires no change to laboratory protocols, it can be used for both existing datasets and future studies, thus adding a new dimension for HLA typing and biomarker studies.
Interferon-lambda (IFN-λ) induces signal transduction and gene expression in human hepatocytes, but not in lymphocytes or monocytes
Authors: Dickensheets Harold , Sheikh Faruk , Park Ogyi , Gao Bin , Donnelly Raymond P
Published: December 2012

Interferon-alpha and interferon-lambda induce distinct functional responses in human hepatocytes, lymphocytes, and monocytes.

This study compared the ability of IFN-α and IFN-λ to induce signal transduction and gene expression in primary human hepatocytes, PBLs, and monocytes. IFN-α drug products are widely used to treat chronic HCV infection; however, IFN-α therapy often induces hematologic toxicities as a result of the broad expression of IFNARs on many cell types, including most leukocytes. rIFN-λ1 is currently being tested as a potential alternative to IFN-α for treating chronic HCV. Although IFN-λ has been shown to be active on hepatoma cell lines, such as HepG2 and Huh-7, its ability to induce responses in primary human hepatocytes or leukocytes has not been examined. We found that IFN-λ induces activation of Jak/STAT signaling in mouse and human hepatocytes, and the ability of IFN-λ to induce STAT activation correlates with induction of numerous ISGs. Although the magnitude of ISG expression induced by IFN-λ in hepatocytes was generally lower than that induced by IFN-α, the repertoire of regulated genes was quite similar. Our findings demonstrate that although IFN-α and IFN-λ signal through distinct receptors, they induce expression of a common set of ISGs in hepatocytes. However, unlike IFN-α, IFN-λ did not induce STAT activation or ISG expression by purified lymphocytes or monocytes. This important functional difference may provide a clinical advantage for IFN-λ as a treatment for chronic HCV infection, as it is less likely to induce the leukopenias that are often associated with IFN-α therapy.
Short-Term Estradiol Administration in Aging Ovariectomized Rats Provides Lasting Benefits for Memory and the Hippocampus: A Role for Insulin-Like Growth Factor-I
Authors: Witty Christine F. , Gardella Layne P. , Perez Maria C. , Daniel Jill M.
Published: December 2012

We previously demonstrated that aged ovariectomized rats that had received prior estradiol treatment in middle age exhibited enhanced spatial memory and increased levels of estrogen receptor (ER)-α in the hippocampus long after estradiol treatment was terminated. The implication for cognition of increased levels of ERα resulting from prior estradiol exposure is unknown. In the absence of estrogens, growth factors, including IGF-I, can induce ERα-mediated transcription through ligand-independent mechanisms. Our current goal was to determine whether IGF-I mediates the ability of short-term exposure to estradiol to exert long-term effects on cognition and the hippocampus of aging females. Ovariectomized middle-aged rats were implanted with estradiol or cholesterol vehicle capsules. After 40 days, all capsules were removed and drug treatments were initiated. Half of each hormone treatment group received chronic intracerebroventricular delivery of the IGF-I receptor antagonist JB1, and the other half received artificial cerebrospinal fluid vehicle. Rats were tested on a spatial memory radial-arm maze task and hippocampi were immunostained for proteins of interest by Western blotting. As expected, previous treatment with estradiol enhanced spatial memory and increased levels of ERα in the hippocampus. JB1 reversed these effects. Previous treatment with estradiol resulted in lasting increases in levels of IGF-I receptors and phosphorylation of ERK/MAPK, a downstream signaling molecule of both ERα and IGF-I receptors, and increased levels of the ERα-regulated protein, choline acetyltransferase. JB1 blocked effects on ERK/MAPK and choline acetyltransferase. Results indicate that activation of IGF-I receptors is necessary for prior estradiol exposure to exert lasting impact on the hippocampus and memory.
Cortisol and Interferon Tau Regulation of Endometrial Function and Conceptus Development in Female Sheep
Authors: Dorniak Piotr , Welsh Thomas H. , Bazer Fuller W. , Spencer Thomas E.
Published: December 2012

During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce prostaglandins (PG) via PG synthase 2 (PTGS2) and cortisol via hydroxysteroid (11-β) dehydrogenase 1 (HSD11B1). Ovarian progesterone induces and PG and IFNT stimulates endometrial HSD11B1 expression and keto-reductase activity as well as many epithelial genes that govern trophectoderm proliferation, migration, and attachment during elongation. The primary aim of these studies was to test the hypothesis that HSD11B1-derived cortisol has a biological role in endometrial function and conceptus development during early pregnancy in sheep. In study 1, cyclic ewes received vehicle, cortisol, PF 915275 (PF; a selective inhibitor of HSD11B1), cortisol and PF, meloxicam (a selective inhibitor of PTGS2), cortisol and meloxicam, recombinant ovine IFNT, or IFNT and PF into the uterus from day 10 to day14 after estrus. Cortisol and IFNT stimulated endometrial HSD11B1 expression and activity, increased endometrial PTGS2 activity and the amount of PG in the uterine lumen, and up-regulated many conceptus elongation-related genes in the endometrium. Some effects of cortisol and IFNT were mediated by PTGS2-derived PG. In study 2, bred ewes received PF 915275 or recombinant ovine IFNT and into the uterus from day 10 to day 14 after mating. Inhibition of HSD11B1 activity in utero prevented conceptus elongation, whereas IFNT rescued conceptus elongation in PF-infused ewes. These results suggest that HSD11B1-derived cortisol mediates, in part, actions of ovarian progesterone and the conceptus on endometrial function and support the hypothesis that IFNT, PG, and cortisol coordinately regulate endometrial functions important for conceptus elongation and implantation during early pregnancy in sheep.
Something Went Wrong on the Way to the Courthouse
Authors: Hyman David A.
Published: December 2012

Almost without exception, law professors dismissed the possibility that the Patient Protection and Affordable Care Act (PPACA) might be unconstitutional — but something went wrong on the way to the courthouse. What explains the epic failure of law professors to accurately predict how Article 3 judges would approach the case? This essay identifies three distinct but complementary factors that might help explain the observed failure. First, instead of conducting a neutral assessment of the actual probabilities, law professors engaged in motivated reasoning, based on their preexisting political and policy preferences. Second, the psychology of constitutional law professors led them to massively overstate the probability of success and suppress any misgivings or cautious hedging. Third, once it became clear that the PPACA was in serious jeopardy, our nation's law professors decided to pursue politics by other means, and organized the academic equivalent of a vigilance committee.
The Affordable Care Act and Reproductive Health: Potential Gains and Serious Challenges
Authors: Sonfield Adam , Pollack Harold A.
Published: December 2012

After nearly a century of failed or incomplete legislative efforts, the Patient Protection and Affordable Care Act (PPACA), enacted by Congress in March 2010, establishes the principle that every American is entitled to affordable and effective health insurance coverage regardless of income or health status. Although many aspects of the act have received broad attention, its impact on reproductive health has received considerably less scrutiny, except when debated through the specific lens of particularly polarized ideological concerns. If fully implemented as planned, the PPACA has the potential to improve reproductive health in the United States in at least three ways: increasing the number of women and men with insurance coverage; increasing the value of insurance coverage for addressing reproductive health needs; and improving access to reproductive health services and information more generally. Several PPACA provisions stand out as having particular importance for reproductive health, including Medicaid family planning expansions, standards for an essential health benefits package, expanded coverage for contraception and other clinical preventive services, and teen pregnancy prevention programs. All these potential gains, however, are threatened by political, economic, and logistical challenges to the PPACA and by flaws in the legislation itself.
What Happens to the Women Who Fall Through the Cracks of Health Care Reform? Lessons from Massachusetts
Authors: Dennis Amanda , Blanchard Kelly , Córdova Denisse , Wahlin Britt , Clark Jill , Edlund Karen , McIntosh Jennifer , Tsikitas Lenore
Published: December 2012

We investigated the impact of Massachusetts health care reform on low-income women's experiences accessing insurance and health services, specifically reproductive health services such as contraception. Our findings suggest that concentrated efforts are needed to make sure that health services are available and accessible to populations who fall through the cracks of health care reform, including immigrants, minors and young adults, and women living outside urban areas. In addition, systems changes are needed to ensure that women going through common life transitions, such as pregnancy, marriage, moving, or graduating from school, have continuous access to insurance, and therefore health services, as their lives change. These groups face barriers enrolling in and maintaining their insurance coverage as well as obtaining timely health care benefits they are eligible for through their insurance benefits or public health programs. Without intervention, many in these groups may delay or avoid seeking health care altogether, which may increase health care disparities in the long term. Family planning providers in Massachusetts have played a critical role in mitigating barriers to insurance and health care. However, recent threats to defund family planning providers call into question the ability of these providers to continue providing much-needed services.