Survival bias may explain the appearance of the obesity paradox in hip fracture patients.

Patients with low-energy hip fractures do not follow the obesity paradox as previously reported. In datasets where injury mechanism is not available, the use of age >50 years (as opposed to commonly used >65 years) as a surrogate for a low-energy hip fracture patients may be a more robust inclusion criterion. PURPOSE: In elderly patients with a hip fracture, limited data suggests that obese patients counterintuitively have improved survival compared to normal-weight patients. This "obesity paradox" may be the byproduct of selection bias. We hypothesized that the obesity paradox would not apply to elderly hip fracture patients. METHODS: The National Surgical Quality Improvement Project dataset identified 71,685 hip fracture patients ≥50 years-of-age with complete body mass index (BMI) data that underwent surgery. Patients were stratified into under and over 75-year-old cohorts (n=18,956 and 52,729, respectively). Within each age group, patients were stratified by BMI class and compared with respect to preoperative characteristics and 30-day mortality. Significant univariate characteristics (p<0.1) were included in multivariate analysis to determine the independent effect of obesity class on 30-day mortality (p<0.05). RESULTS: Multivariate analysis of <75-year-old patients with class-III obesity were more likely to die within 30-days than similarly aged normal-weight patients (OR 1.91, CI 1.06-3.42, p=0.030). Multivariate analysis of ≥75-year-old overweight (OR 0.69, CI 0.62-0.77, p<0.001), class-I obese (OR 0.62, CI 0.51-0.74, p<0.001), or class-II obese (OR=0.69, CI 0.50-0.95, p=0.022) patients were less likely to die within 30-days when compared to similarly aged normal-weight patients. CONCLUSIONS: Our data suggest that obesity is a risk factor for mortality in low-energy hip fracture patients, but the appearance of the "obesity paradox" in elderly hip fracture patients results from statistical bias that is only evident upon subgroup analysis.

Calpain-activated mTORC2/Akt pathway mediates airway smooth muscle remodelling in asthma.

BACKGROUND: Allergic asthma is characterized by inflammation and airway remodelling. Airway remodelling with excessive deposition of extracellular matrix (ECM) and larger smooth muscle mass are correlated with increased airway responsiveness and asthma severity. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodelling. However, the role of calpain in airway smooth muscle remodelling remains unknown. OBJECTIVE: To investigate the role of calpain in asthmatic airway remodelling as well as the underlying mechanism. METHODS: The mouse asthma model was made by ovalbumin sensitization and challenge. Calpain conditional knockout mice were studied in the model. Airway smooth muscle cells (ASMCs) were isolated from smooth muscle bundles in airway of rats. Cytokines IL-4, IL-5, TNF-α, and TGF-ß1, and serum from patients with asthma were selected to treated ASMCs. Collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs were analysed. RESULTS: Inhibition of calpain using calpain knockout mice attenuated airway smooth muscle remodelling in mouse asthma models. Cytokines IL-4, IL-5, TNF-α, and TGF-ß1, and serum from patients with asthma increased collagen-I synthesis, cell proliferation, and phosphorylation of Akt in ASMCs, which were blocked by the calpain inhibitor MDL28170. Moreover, MDL28170 reduced cytokine-induced increases in Rictor protein, which is the most important component of mammalian target of rapamycin complex 2 (mTORC2). Blockage of the mTORC2 signal pathway prevented cytokine-induced phosphorylation of Akt, collagen-I synthesis, and cell proliferation of ASMCs and attenuated airway smooth muscle remodelling in mouse asthma models. CONCLUSIONS AND CLINICAL RELEVANCE: Our results indicate that calpain mediates cytokine-induced collagen-I synthesis and proliferation of ASMCs via the mTORC2/Akt signalling pathway, thereby regulating airway smooth muscle remodelling in asthma.

Phase I study of weekly nab-paclitaxel + weekly cetuximab + intensity-modulated radiation therapy (IMRT) in patients with stage III-IVB head and neck squamous cell carcinoma (HNSCC).

BACKGROUND: There is a clinical need to improve the efficacy of standard cetuximab + concurrent intensity-modulated radiation therapy (IMRT) for patients with locally and/or regionally advanced HNSCC. Taxanes have radiosensitizing activity against HNSCC, and nab-paclitaxel may offer therapeutic advantage in comparison with other taxanes. PATIENTS AND METHODS: This was a single-institution phase I study with a modified 3 + 3 design. Four dose levels (DLs) of weekly nab-paclitaxel were explored (30, 45, 60, and 80 mg/m(2)), given with standard weekly cetuximab (450 mg/m(2) loading dose followed by 250 mg/m(2) weekly) and concurrent IMRT (total dose, 70 Gy). RESULTS: Twenty-five eligible patients (20 M, 5 F) enrolled, with median age 58 years (range, 46-84 years). Primary tumor sites were oropharynx, 19 (10 human papillomavirus [HPV] pos, 8 HPV neg, 1 not done); neck node with unknown primary, 2; larynx 2; and oral cavity and maxillary sinus, 1 each. Seven patients had received prior induction chemotherapy. Maximum tolerated dose (MTD) was exceeded at DL4 (nab-paclitaxel, 80 mg/m(2)) with three dose-limiting toxicities (DLTs) (grade 3 neuropathy, grade 3 dehydration, with grade 3 mucositis grade 3 anemia) among five assessable patients. There was only one DLT (grade 3 supraventricular tachycardia) among six patients at DL3 (nab-paclitaxel, 60 mg/m(2)), and this was deemed the MTD. Among 23 assessable patients, the most common ≥ g3 AEs were lymphopenia 100%, functional mucositis 65%, and pain in throat/oral cavity 52%. At a median follow-up of 33 months, 2-year failure-free survival (FFS) is 65% [95% confidence interval (CI) 42% to 81%] and 2-year overall survival (OS) is 91% (95% CI 69-97). CONCLUSION: The recommended phase II dose for nab-paclitaxel is 60 mg/m(2) weekly when given standard weekly cetuximab and concurrent IMRT. This regimen merits further study as a nonplatinum alternative to IMRT + cetuximab alone. CLINICALTRIALSGOV ID: NCT00736619.

CYP11A1 microsatellite (tttta)n polymorphism in PCOS women from South India.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a condition with central feature of hyperandrogensism that affects 5-12 % of women worldwide. P450sec the cholesterol side chain cleavage enzyme encoded by CYP11A1 gene is instrumental in the synthesis of sex hormones. A promoter pentanucleotide repeat (tttta)(n) polymorphism of this gene is reported to be associated with several hormone related diseases including PCOS. Here we aimed to examine the involvement of CYP11A1 polymorphism with PCOS susceptibility in a case-control study conducted among South Indian women. METHODS: A total of 542 subjects comprised of 267 PCOS patients and 275 controls were recruited. DNA was extracted from blood and CYP11A1 (tttta)(n) polymorphism was genotyped by PCR-PAGE. RESULTS: Fifteen different alleles ranging between 2-16 repeats were identified in the studied group and the most frequent allele observed in controls was of 8 repeats. The presence of >8 repeat allele was common in patients (64 % vs. 38 %) and showed a three-fold risk for PCOS susceptibility than controls (OR = 2.93; p < 0.05). PCOS women with higher BMI were markedly elevated in early quartile (p < 0.05). CONCLUSION: CYP11A1 (tttta)(n) repeat polymorphism appeared to be a potential molecular marker for PCOS risk in our population. Gene-gene and gene-environmental interactions with respect to obesity may play a role in the early onset of this multifactorial condition. This is the first report from South India; however, replicative studies considering other probable causative factors for PCOS risk are warranted.

Interface magnetism in epitaxial BiFeO3-La0.7Sr0.3MnO3 heterostructures integrated on Si(100).

We report on the heteroepitaxial growth of ferroelectric (FE)-antiferromagnetic (AFM) BiFeO3 (BFO) on ferromagnetic La0.7Sr0.3MnO3 (LSMO), integrated on Si(100) using pulsed laser deposition via the domain matching epitaxy paradigm. The BFO/LSMO films were epitaxially grown on Si(100) by introducing epitaxial layers of SrTiO3/MgO/TiN. X-ray diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, X-ray photo absorption spectroscopy, and atomic force microscopy were employed to fully characterize the samples. Furthermore, we have investigated the magnetic behavior of this five layer heterostructure, in which a d(5) system (Fe(3+)) manifested in FE-AFM BFO is epitaxially conjoined at the interface to a multivalent transition metal ion such as Mn(3+)/Mn(4+) in LSMO. The temperature- and magnetic field-dependent magnetization measurements reveal an unexpected enhancement in magnetic moment and improved magnetic hysteresis squareness originating from the BFO/LSMO interface. We observe a stronger temperature dependence of HEB when the polarity of field cooling is negative as compared to positive field cooling. We believe such an enhancement in magnetic moment and magnetic coupling is likely directly related to an electronic orbital reconstruction at the interface and complex interplay between orbital and spin degrees of freedom, similar to what has previously been reported in the literature. Future work will involve the linearly polarized X-ray absorption measurements to prove this hypothesis. This work represents a starting step toward the realization of magneto-electronic devices integrated with Si(100).

Dilute acid pretreatment and enzymatic hydrolysis of sorghum biomass for sugar recovery--a statistical approach.

Sorghum is one of the commercially feasible lignocellulosic biomass and has a great potential of being sustainable feedstock for renewable energy. As with any lignocellulosic biomass, sorghum also requires pretreatment which increases its susceptibility to hydrolysis by enzymes for generating sugars which can be further fermented to alcohol. In the present study, sorghum biomass was evaluated for deriving maximum fermentable sugars by optimizing various pretreatment parameters using statistical optimization methods. Pretreatment studies were done with H2SO4, followed by enzymatic saccharification. The efficiency of the process was evaluated on the basis of production of the total reducing sugars released during the process. Compositional analysis was done for native as well as pretreated biomass and compared. The biomass pretreated with the optimized conditions could yield 0.408 g of reducing sugars /g of pretreated biomass upon enzymatic hydrolysis. The cellulose content in the solid portion obtained after pretreatment using optimised conditions was found to be increased by 43.37% with lesser production of inhibitors in acid pretreated liquor.

Ferromagnetism in graphene nanoribbons: split versus oxidative unzipped ribbons.

Two types of graphene nanoribbons: (a) potassium-split graphene nanoribbons (GNRs), and (b) oxidative unzipped and chemically converted graphene nanoribbons (CCGNRs) were investigated for their magnetic properties using the combination of static magnetization and electron spin resonance measurements. The two types of ribbons possess remarkably different magnetic properties. While a low-temperature ferromagnet-like feature is observed in both types of ribbons, such room-temperature feature persists only in potassium-split ribbons. The GNRs show negative exchange bias, but the CCGNRs exhibit a "positive exchange bias". Electron spin resonance measurements suggest that the carbon-related defects may be responsible for the observed magnetic behavior in both types of ribbons. Furthermore, information on the proton hyperfine coupling strength has been obtained from hyperfine sublevel correlation experiments performed on the GNRs. Electron spin resonance finds no evidence for the presence of potassium (cluster) related signals, pointing to the intrinsic magnetic nature of the ribbons. Our combined experimental results may indicate the coexistence of ferromagnetic clusters with antiferromagnetic regions leading to disordered magnetic phase. We discuss the possible origin of the observed contrast in the magnetic behaviors of the two types of ribbons studied.

Cyclobacterium qasimii sp. nov., a psychrotolerant bacterium isolated from Arctic marine sediment.

A novel Gram-stain-negative, horseshoe-shaped, non-motile bacterium, designated strain M12-11B(T), was isolated from a marine sediment sample collected at a depth of 200 m from Kongsfjorden, Svalbard. The colony colour was orangish red due to the presence of carotenoids. Fatty acids were dominated by branched and unsaturated fatty acids (90.8 %), with a high abundance of iso-C(15 : 0) (14.9 %), anteiso-C(15 : 0) (11.4 %), iso-C(15 : 1) G (13.1 %), C(15 : 1)ω6c (5.4 %), C(17 : 1)ω6c (6.7 %), summed feature 3 (C(16 : 1)ω7c and/or C(16 : 1)ω6c; 9.3 %) and summed feature 9 (10-methyl C(16 : 0) and/or iso-C(17 : 1)ω9c; 5.9 %). Strain M12-11B(T) contained MK-7 as the major respiratory quinone. The polar lipids consisted of phosphatidylcholine, phosphatidylethanolamine, one unidentified aminolipid and three unidentified lipids. Based on 16S rRNA gene sequence similarities, the type strains of Cyclobacterium amurskyense, Cyclobacterium marinum and Cyclobacterium lianum were most closely related to M12-11B(T) with sequence similarities of 98.2, 96.8 and 93.3 %, respectively. Other members of the family Cyclobacteriaceae had sequence similarities of <92.0 %. However, DNA-DNA hybridization with Cyclobacterium amurskyense KCTC 12363(T) and Cyclobacterium marinum DSM 745(T) showed relatedness values of only 24.5 and 32.5 % with respect to strain M12-11B(T). Based on the results of DNA-DNA hybridization experiments and phenotypic and chemotaxonomic data, it appears that strain M12-11B(T) represents a novel species of the genus Cyclobacterium, for which the name Cyclobacterium qasimii sp. nov. is proposed; the type strain is M12-11B(T) (= KCTC 23011(T) = NBRC 106168(T)) and it has a DNA G+C content of 40.5 mol%.

Barostat or dynamic balloon distention test: which technique is best suited for esophageal sensory testing?

Esophageal sensation is commonly assessed by barostat-assisted balloon distension (BBD) or dynamic balloon distension (DBD) technique, but their relative merits are unknown. Our aim was to compare the usefulness and tolerability of both techniques. Sixteen healthy volunteers (male/female = 6/10) randomly underwent graded esophageal balloon distensions, using either BBD (n= 8) or DBD (n= 8). BBD was performed by placing a 5-cm long highly compliant balloon attached to a barostat, and DBD by placing a 5-cm long balloon attached to a leveling container. Intermittent phasic balloon distensions were performed in increments of 6 mm Hg. Sensory thresholds and biomechanical properties were assessed and compared. Sensory thresholds for first perception (mean ± standard deviation; 21 ± 6 vs. 21.2 ± 5, mm Hg, P= 0.9), discomfort (38 ± 8 vs. 35 ± 9, P= 0.5), and pain (44 ± 4 vs. 45 ± 3, P= 0.7) were similar with BBD and DBD techniques. However, more subjects tolerated DBD (7/8, 88%) when compared with BBD (4/8, 50%). Forceful expulsion of balloon into stomach (n= 4), pulling around the mouth (n= 4), chest discomfort (n= 2) and retching (n= 2) were overlapping reasons for intolerance with BBD. Esophageal wall distensibility was similar with both techniques. Both techniques provided comparable data on biomechanical properties. However, DBD was better tolerated than BBD for evaluation of esophageal sensation. Hence, we recommend DBD for performing esophageal balloon distension test.

Retraction. Cyclobacterium qasimii sp. nov., a psychrotolerant bacterium isolated from a marine sediment of Kongsfjorden, Svalbard.

The authors would like to retract this publication in order to improve the chemotaxonomic data as it has become apparent that there are inconsistencies in the data presented in this paper. This paper has been retracted from IJSEM Papers in Press and will not be published in print in IJSEM.

Adenosine modulates oesophageal sensorimotor function in humans.

BACKGROUND AND AIMS: Adenosine mediates somatic and visceral pain, but its effects on gut visceral nociception are unknown. The aim of the present study was to test the hypothesis that adenosine alters oesophageal sensorimotor function. METHODS: In a double-blind, randomised, placebo-controlled study, 14 healthy volunteers (M/F = 4/10) received either intravenous adenosine 100 microg/kg/min or placebo infusion. Prior to and during infusion, all subjects underwent stepwise graded oesophageal balloon distensions using impedance planimetry. Sensory responses and biomechanical properties were assessed and compared. RESULTS: Adenosine significantly lowered thresholds for first perception (median (25th-75th), cm H(2)O; 10 (10-20) vs 30 (20-30), p = 0.007), discomfort (40 (30-40) vs 50 (50-60), p = 0.011) and pain (50 (40-60) vs 70 (60-70), p = 0.007) when compared with placebo. Also, the median threshold pressures required to induce first perception (p = 0.017), discomfort (p = 0.024) and pain (p = 0.026) were lower when compared with baseline. The cross-sectional area of the oesophagus increased (p = 0.032), and the circumferential wall tension/strain relationship shifted to the left (the wall became stiffer) (p = 0.043) after adenosine, when compared with baseline or placebo. CONCLUSIONS: Adenosine can induce visceral hyperalgesia and decrease oesophageal distensibility in humans. These evoked sensorimotor changes are similar to those described in patients with functional oesophageal (non-cardiac) chest pain. Thus, adenosine modulates oesophageal sensorimotor function and may play a role in the pathogenesis of functional chest pain.

Indian Resuscitation Council (IRC) suggested guidelines for Comprehensive Cardiopulmonary Life Support (CCLS) for suspected or confirmed coronavirus disease (COVID-19) patient.

Management of the recent outbreak of the novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) remains challenging. The challenges are not only limited to its preventive strategies, but also extend to curative treatment, and are amplified during the management of critically ill patients with COVID-19. Older persons with comorbidities like diabetes mellitus, cardiac diseases, hepatic impairment, renal disorders and respiratory pathologies or immune impairing conditions are more vulnerable and have a higher mortality from COVID-19. Earlier, the Indian Resuscitation Council (IRC) had proposed the Comprehensive Cardiopulmonary Life Support (CCLS) for management of cardiac arrest victims in the hospital setting. However, in patients with COVID-19, the guidelines need to be modified,due to various concerns like differing etiology of cardiac arrest, virulence of the virus, risk of its transmission to rescuers, and the need to avoid or minimize aerosolization from the patient due to various interventions. There is limited evidence in these patients, as the SARS-CoV-2 is a novel infection and not much literature is available with high-level evidence related to CPR in patients of COVID-19. These suggested guidelines are a continuum of CCLS guidelines by IRC with an emphasis on the various challenges and concerns being faced during the resuscitative management of COVID-19 patients with cardiopulmonary arrest.

Realizing the 'hindered charge ordered phase' in nanoscale charge ordered manganites: magnetization, magneto-transport and EPR investigations.

We report three prominent observations made on the nanoscale charge ordered (CO) manganites RE(1-x)AE(x)MnO(3) (RE = Nd,Pr; AE = Ca; x = 0.5) probed by temperature dependent magnetization and magneto-transport, coupled with electron magnetic/paramagnetic resonance spectroscopy (EMR/EPR). First, evidence is presented to show that the predominant ground state magnetic phase in nanoscale CO manganites is ferromagnetic and it coexists with a residual anti-ferromagnetic phase. Secondly, the shallow minimum in the temperature dependence of the EPR linewidth shows the presence of a charge ordered phase in nanoscale manganites which was shown to be absent from the DC static magnetization and transport measurements. Thirdly, the EPR linewidth, reflective of spin dynamics, increases significantly with a decrease of particle size in CO manganites. We discuss the interesting observations made on various samples of different particle sizes and give possible explanations. We have shown that EMR spectroscopy is a highly useful technique to probe the 'hindered charge ordered phase' in nanoscale CO manganites, which is not possible by static DC magnetization and transport measurements.

Bacterial diversity and bioprospecting for cold-active lipases, amylases and proteases, from culturable bacteria of kongsfjorden and Ny-alesund, Svalbard, Arctic.

Culturable bacterial diversity of seven marine sediment samples of Kongsfjorden and a sediment and a soil sample from Ny-Alesund, Svalbard, Arctic was studied. The bacterial abundance in the marine sediments of Kongsfjorden varied marginally (0.5 x 10(3)-1.3 x 10(4) cfu/g sediment) and the bacterial number in the two samples collected from the shore of Ny-Alesund also was very similar (0.6 x 10(4) and 3.4 x 10(4), respectively). From the nine samples a total of 103 bacterial isolates were obtained and these isolates could be grouped in to 47 phylotypes based on the 16S rRNA gene sequence belonging to 4 phyla namely Actinobacteria, Bacilli, Bacteroidetes and Proteobacteria. Representatives of the 47 phylotypes varied in their growth temperature range (4-37 degrees C), in their tolerance to NaCl (0.3-2 M NaCl) and growth pH range (2-11). Representatives of 26 phylotypes exhibited amylase and lipase activity either at 5 or 20 degrees C or at both the temperatures. A few of the representatives exhibited amylase and/or lipase activity only at 5 degrees C. None of the phylotypes exhibited protease activity. Most of the phylotypes (38) were pigmented. Fatty acid profile studies indicated that short chain fatty acids, unsaturated fatty acids, branched fatty acids, the cyclic and the cis fatty acids are predominant in the psychrophilic bacteria.

A gene-based avian influenza vaccine in poultry.

Highly pathogenic avian influenza A (HPAI) viruses, specifically H5N1 strains, cause widespread morbidity and mortality in domestic and wild bird populations, and recent outbreaks have resulted in severe economic losses. Although still largely confined to birds, more than 300 human cases resulting in deaths have been reported to the World Health Organization. These sporadic human cases result from direct transmission from infected birds; however, a sustained outbreak of HPAI H5N1 increases the potential for the emergence of a human pandemic strain. One approach to the containment of HPAI H5N1 is the development of vaccines for use in poultry. Currently, the majority of avian influenza vaccines for poultry are traditional whole-virus vaccines produced in eggs. Although highly efficacious, these vaccines are hindered by long production times, inflexibility in quickly altering antigenic composition, and limited breadth of protection. Newer vaccines with more efficient manufacturing processes, enhanced efficacy, and cross-protection against multiple strains would improve preparedness. Reverse genetics technology has provided one such method, and emerging gene-based vaccines offer another approach that reduces dependence on egg-based production and human exposure to pathogenic viruses. Gene-based vaccines also provide rapid manufacturing, enhanced precision and versatility, and the capacity to protect against a broad range of viral subtypes. Vectors for these vaccines include replication-defective viruses, bacterial vectors, and DNA. Here we review the features of gene-based vaccination that may facilitate the control of HPAI H5N1 in poultry, and highlight the development of a hemagglutinin-based multivalent DNA vaccine that confers protection in mice and chickens.

Cross-country transport and isolation and identification of Streptococcus pneumoniae by use of alternate sources of blood supplemented media among laboratories in India.

Background: The isolation of S. pneumoniae (Sp) depends on specimen integrity / transport, media and expertise. The non-availability of sheep blood agar poses a challenge in identification of colonial morphology and identification in India. Methods: Laboratories processed swabs containing either pure Sp or Sp in mixed cultures with a second (confounding) bacterium shipped across the country in cold conditions. Duplicate set of swabs was shipped back to the central laboratory to assess the impact of shipping on culture viability. The identical swab was cultured on sheep, human blood and one additional agar plate used in the laboratory. Results: 46/60(77%) of cultures containing only Sp were correctly identified. In specimens where Sp was present in mixed culture, the proportion of isolates in which Sp was correctly identified varied, with most variability attributed to the particular confounding organism rather than the media. There was no discernible impact of temperature-controlled (4-6°C) transport on the isolation of Sp from culture swabs. Conclusions: The study clearly elucidates the ability of laboratories for isolation of S. pneumoniae on human blood agar in resource limited settings. The results highlight the difficulties inherent in correctly identifying pathogens in mixed cultures in needs improvement using standardized tests across the study centers. The study also reaffirms the ability to transport biological specimens over long geographical distances without loss.

Meningitis in a butcher.

Streptococcus suis is a common pathogen in swine and infection in humans is rarely reported. When it does occur, it is considered an occupational risk associated with the handling of carcasses. Meningitis is one of the most life-threatening manifestations of S suis infection. This case of meningitis in a butcher is reported to create awareness of this zoonotic disease. The report highlights the importance of an occupational history and a meticulous general physical examination looking for cuts and abrasions in patients with suspicion of meningitis.

Development, content validity, and cross-cultural adaptation of a patient-reported outcome measure for real-time symptom assessment in irritable bowel syndrome.

BACKGROUND: End-of-day questionnaires, which are considered the gold standard for assessing abdominal pain and other gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS), are influenced by recall and ecological bias. The experience sampling method (ESM) is characterized by random and repeated assessments in the natural state and environment of a subject, and herewith overcomes these limitations. This report describes the development of a patient-reported outcome measure (PROM) based on the ESM principle, taking into account content validity and cross-cultural adaptation. METHODS: Focus group interviews with IBS patients and expert meetings with international experts in the fields of neurogastroenterology & motility and pain were performed in order to select the items for the PROM. Forward-and-back translation and cognitive interviews were performed to adapt the instrument for the use in different countries and to assure on patients' understanding with the final items. KEY RESULTS: Focus group interviews revealed 42 items, categorized into five domains: physical status, defecation, mood and psychological factors, context and environment, and nutrition and drug use. Experts reduced the number of items to 32 and cognitive interviewing after translation resulted in a few slight adjustments regarding linguistic issues, but not regarding content of the items. CONCLUSIONS AND INFERENCES: An ESM-based PROM, suitable for momentary assessment of IBS symptom patterns was developed, taking into account content validity and cross-cultural adaptation. This PROM will be implemented in a specifically designed smartphone application and further validation in a multicenter setting will follow.

A high-resolution anorectal manometry parameter based on integrated pressurized volume: A study based on 204 male patients with constipation and 26 controls.

BACKGROUND: Conventional anorectal manometric parameters based on linear waves cannot properly predict balloon expulsion (BE) time. We aimed to determine the correlation between integrated pressurized volume (IPV) parameters during simulated evacuation (SE) and BE time in healthy individuals and constipated patients and to assess the correlation between each parameter and symptoms. METHODS: A total of 230 male participants (including 26 healthy volunteers and 204 chronically constipated patients) underwent high-resolution anorectal manometry (HRAM) and BE tests. The IPV was calculated by multiplying the amplitude, distance, and time from the HRAM profile. Receiver operating characteristic curve (ROC) analysis and partial least square regression (PLSR) were performed. KEY RESULTS: ROC analysis indicated that the IPV ratio between the upper 1 cm and lower 4 cm of the anal canal was more effective for predicting BE time (area under the curve [AUC]: 0.74, 95% confidence interval [CI]: 0.67-0.80, P < .01) than the conventional anorectal parameters, including defecation index and rectoanal gradient (AUC: 0.60, 95% CI: 0.52-0.67, P = .01). PLSR analysis of a linear combination of IPV parameters yielded an AUC of 0.79. Moreover, the IPV ratio showed a greater clinical correlation with patient symptoms than conventional parameters. CONCLUSIONS AND INFERENCES: The IPV parameters and the combination of IPV parameters via PLSR were more significantly correlated with BE time than the conventional parameters. Thus, this study presents a useful diagnostic tool for the evaluation of pathophysiologic abnormalities in dyssynergic defecation using IPV and BE time.

Ectopic expression of cyclin D1 prevents activation of gene transcription by myogenic basic helix-loop-helix regulators.

Activation of muscle gene transcription in differentiating skeletal myoblasts requires their withdrawal from the cell cycle. The effects of ectopic cyclin expression on activation of muscle gene transcription by myogenic basic helix-loop-helix (bHLH) regulators were investigated. Ectopic expression of cyclin D1, but not cyclins A, B1, B2, C, D3, and E, inhibited transcriptional activation of muscle gene reporter constructs by myogenic bHLH regulators in a dose-dependent manner. Ectopic expression of cyclin D1 inhibited the activity of a myogenic bHLH regulator mutant lacking the basic region protein kinase C site, indicating that phosphorylation of this site is not relevant to the mechanism of inhibition. Analysis of cyclin D1 mutants revealed that the C-terminal acidic region was required for inhibition of myogenic bHLH regulator activity, whereas an intact N-terminal pRb binding motif was not essential. Together, these results implicate expression of cyclin D1 as a central determinant of a putatively novel mechanism that links positive control of cell cycle progression to negative regulation of genes expressed in differentiated myocytes.