Assessment of CT perfusion indices of the clinicoradiological response to anti-tubercular therapy in patients with intestinal tuberculosis.

AIM: To explore the possibility of using a novel technique, CT perfusion imaging, to monitor the response to anti-tubercular therapy (ATT) in patients with intestinal tuberculosis. MATERIALS AND METHODS: A prospective observational study was performed in adults with treatment naive-intestinal tuberculosis. Clinical, endoscopic, and conventional radiological findings of patients were compared at baseline and post-ATT. CT perfusion imaging was performed with recording of six perfusion parameters (blood flow, blood volume, mean transit time, time to peak, maximum peak intensity, and permeability/blood flow extraction). RESULTS: Twenty-two patients (13 women, 59%) with a median age of 25 years were recruited. The terminal ileum and ileocaecal junction were the most frequent sites of involvement (59%), with multiple segments of the intestine being involved in 16 patients (73%). Median duration of ATT was 6 months (range 6-10 months). Complete clinical response was observed in 22/22 (100%) patients, endoscopic response in 12/12 (100%) patients, and radiological response in 10/13 (76%) patients. There was a significant decrease in mean blood flow, blood volume, maximum peak intensity, and an increase in mean transit time and time to peak on follow-up CT perfusion imaging performed after 6 months of ATT. CONCLUSION: Significant alterations in CT perfusion parameters were demonstrated following treatment, consistent with a decline in inflammation and vascularity. CT perfusion imaging of the bowel is a novel means to assess the radiological response to ATT in intestinal tuberculosis, although at the cost of a higher dose of radiation exposure.

Points to consider in seeking biosafety approval for research, testing, and environmental release of experimental genetically modified biocontrol products during research and development.

Novel genetically modified biological control products (referred to as "GM biocontrol products") are being considered to address a range of complex problems in public health, conservation, and agriculture, including preventing the transmission of vector-borne parasitic and viral diseases as well as the spread of invasive plant and animal species. These interventions involve release of genetically modified organisms (GMOs) into the environment, sometimes with intentional dissemination of the modification within the local population of the targeted species, which presents new challenges and opportunities for regulatory review and decision-making. Practices developed for GMOs, primarily applied to date for GM crops may need to be adapted to accommodate different types of organisms, such as insects, and different technologies, such as gene drive. Developers of new GM biocontrol products would benefit from an early understanding of safety data and information that are likely to be required within the regulatory dossier for regulatory evaluation and decision making. Here a generalizable tool drawing from existing GM crop dossier requirements, forms, and relevant experience is proposed to assist researchers and developers organize and plan their research and trialing. This tool requires considering specifics of each investigational product, their intended use, and country specific requirements at various phases of potential product development, from laboratory research through contained field testing and experimental release into the environment. This may also be helpful to risk assessors and regulators in supporting their systematic and rigorous evaluation of new biocontrol products.

Hydrodynamically Coupled Brownian Dynamics: A coarse-grain particle-based Brownian dynamics technique with hydrodynamic interactions for modeling self-developing flow of polymer solutions.

We present a novel coarse-grain particle-based simulation technique for modeling self-developing flow of dilute and semi-dilute polymer solutions. The central idea in this paper is the two-way coupling between a mesoscopic polymer model and a phenomenological fluid model. As our polymer model, we choose Responsive Particle Dynamics (RaPiD), a Brownian dynamics method, which formulates the so-called "conservative" and "transient" pair-potentials through which the polymers interact besides experiencing random forces in accordance with the fluctuation dissipation theorem. In addition to these interactions, our polymer blobs are also influenced by the background solvent velocity field, which we calculate by solving the Navier-Stokes equation discretized on a moving grid of fluid blobs using the Smoothed Particle Hydrodynamics (SPH) technique. While the polymers experience this frictional force opposing their motion relative to the background flow field, our fluid blobs also in turn are influenced by the motion of the polymers through an interaction term. This makes our technique a two-way coupling algorithm. We have constructed this interaction term in such a way that momentum is conserved locally, thereby preserving long range hydrodynamics. Furthermore, we have derived pairwise fluctuation terms for the velocities of the fluid blobs using the Fokker-Planck equation, which have been alternatively derived using the General Equation for the Non-Equilibrium Reversible-Irreversible Coupling (GENERIC) approach in Smoothed Dissipative Particle Dynamics (SDPD) literature. These velocity fluctuations for the fluid may be incorporated into the velocity updates for our fluid blobs to obtain a thermodynamically consistent distribution of velocities. In cases where these fluctuations are insignificant, however, these additional terms may well be dropped out as they are in a standard SPH simulation. We have applied our technique to study the rheology of two different concentrations of our model linear polymer solutions. The results show that the polymers and the fluid are coupled very well with each other, showing no lag between their velocities. Furthermore, our results show non-Newtonian shear thinning and the characteristic flattening of the Poiseuille flow profile typically observed for polymer solutions.

Effect of maternal oxygen inhalation on foetal free radical activity: a prospective, randomized trial.

BACKGROUND: Maternal inhalation of 35-40% oxygen concentration has no significant effect on foetal partial pressure of oxygen, and 60-100% produced maternal and foetal hyperoxia with increased free radical activity. The benefit of 50% maternal oxygen inhalation on foetal oxygenation, oxidant stress and total antioxidant status (TAS) during Caesarean section (CS) has not been simultaneously evaluated. METHODS: In this prospective, randomized, controlled trial 120 ASA physical status I-II, term pregnant women were recruited to elective CS (n = 60) and emergency CS (n = 60) and received either 50% oxygen or air inhalation following subarachnoid block (SAB). Patients and investigators were blinded to the inhaled oxygen concentration. The primary outcome of the study was foetal umbilical artery (UA) malondialdehyde (MDA) at birth. RESULTS: In both elective and emergency CS, there was no difference in foetal oxidative stress and TAS in spite of increase in maternal PaO2. In elective CS, maternal MDA was higher at delivery in mothers breathing 50% oxygen as compared to their own baseline values (P = 0.04). In emergency CS, maternal TAS at 10 min was lower in mothers inhaling 50% oxygen as compared to air (P = 0.01). The average duration of maternal oxygen supplementation was ~10.3 min in elective and ~7.4 min in emergency CS. Neonatal outcome, episodes of maternal hypotension and oxygen desaturation were similar in both the groups. CONCLUSION: Brief duration of 50% oxygen maternal inhalation during elective or emergency CS did not significantly affect foetal MDA and TAS under SAB.

Correlation of Serum Vitamin A Levels with Disease Activity Indices and Colonic IL-23R and FOXP3 mRNA Expression in Ulcerative Colitis Patients.

Genome-wide association studies have identified IL-23 receptor (IL-23R) as a susceptibility locus for the pathogenesis of ulcerative colitis (UC), which is characterized by exaggerated Th2/Th17 response. Studies have shown that vitamin A (VA) reduces disease progression by promoting FOXP3⁺ T cells and curbing Th17 cells. In this study, we explored the association of colonic IL-23R and FOXP3 expression in fifty-one UC patients (23 in remission and 28 with active disease) with serum VA levels and disease activity. We observed that decreased serum VA levels were associated with increased disease activity. However, there was no significant difference in mucosal IL-23R and FOXP3 expression in UC patients with moderate-to-severe disease activity compared to those in remission. Also, no significant correlation was drawn between serum VA levels and mucosal IL-23R and FOXP3 expression. Our study suggests that even after an established role of VA in inhibiting Th17 responses in mice models and humans, serum VA levels and disease activity do not correlate with FOXP3 and IL-23R expression in colonic mucosa of UC patients.

I.V. paracetamol as an adjunct to patient-controlled epidural analgesia with levobupivacaine and fentanyl in labour: a randomized controlled study.

BACKGROUND: Use of i.v. paracetamol for postoperative pain is well documented, but it is unclear if it can reduce the consumption of opioids during patient-controlled epidural analgesia (PCEA) in labouring parturients. METHODS: In this randomized, double-blind, placebo-controlled clinical trial conducted in a tertiary care hospital, 80parturients were randomly assigned to two groups of 40 each, to receive either 1000 mg (100 ml) i.v. paracetamol or 100 ml normal saline as placebo, 30 min before the procedure. After insertion of the epidural catheter, all patients received 10 ml of levobupivacaine 0.1% with 2 µg ml-1 fentanyl, followed by continuous background epidural infusion of 6 ml h-1 with a provision of patient-controlled bolus 5 ml of same drug with a lock-out interval of 12 min.The primary outcome was hourly mean consumption of levobupivacaine and fentanyl mixture (ml.h-1). Secondary outcomes included pain score ,: sensory and motor block, haemodynamic parameters of mother, duration of second stage of labour, mode of delivery, Apgar scores, foetal heart rate and adverse effects. RESULTS: The hourly mean drug consumption in the Paracetamol group was significantly lower as compared with the Placebo group (7.03 ml.h-1, SD 0.83 vs. 8.12 ml.h-1, SD 1.34; p < 0.001). The mean number of boluses taken were also significantly less in the paracetamol group (1.00, SD 0.93 vs. 1.43, SD 0.90; p = 0.036). Pain scores decreased in both the groups without significant inter-group differences. CONCLUSIONS: Use of 1000 mg i.v. paracetamol decreases the mean hourly drug consumption through epidural route. Thus i.v. paracetamol is a safe and effective adjunct to PCEA in labour analgesia. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry-India (http://ctri.nic.in/Clinicaltrials/login.php), trial registration number 2013/09/003968.

Coarse-grained simulations for flow of complex soft matter fluids in the bulk and in the presence of solid interfaces.

We present a coarse-grained particle-based simulation technique for modeling flow of complex soft matter fluids such as polymer solutions in the presence of solid interfaces. In our coarse-grained description of the system, we track the motion of polymer molecules using their centers-of-mass as our coarse-grain co-ordinates and also keep track of another set of variables that describe the background flow field. The coarse-grain motion is thus influenced not only by the interactions based on appropriate potentials used to model the particular polymer system of interest and the random kicks associated with thermal fluctuations, but also by the motion of the background fluid. In order to couple the motion of the coarse-grain co-ordinates with the background fluid motion, we use a Galilean invariant, first order Brownian dynamics algorithm developed by Padding and Briels [J. Chem. Phys. 141, 244108 (2014)], which on the one hand draws inspiration from smoothed particle hydrodynamics in a way that the motion of the background fluid is efficiently calculated based on a discretization of the Navier-Stokes equation at the positions of the coarse-grain coordinates where it is actually needed, but also differs from it because of the inclusion of thermal fluctuations by having momentum-conserving pairwise stochastic updates. In this paper, we make a few modifications to this algorithm and introduce a new parameter, viz., a friction coefficient associated with the background fluid, and analyze the relationship of the model parameters with the dynamic properties of the system. We also test this algorithm for flow in the presence of solid interfaces to show that appropriate boundary conditions can be imposed at solid-fluid interfaces by using artificial particles embedded in the solid walls which offer friction to the real fluid particles in the vicinity of the wall. We have tested our method using a model system of a star polymer solution at the overlap concentration.

Post-operative analgesia using intermittent vs. continuous adductor canal block technique: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Intermittent boluses for neural blockade provide better post-operative analgesia when compared to continuous infusion. However, these techniques of administration have not yet been compared while performing adductor canal block (ACB). We compared intermittent vs. continuous ACB for managing post-operative pain following anterior cruciate ligament (ACL) reconstruction. The primary endpoint was total morphine consumption for 24 h post-operatively in both the groups. Secondary outcomes included evaluation of pain scores and opioid-related side effects. METHODS: After ethics board approval, subjects presenting for ACL reconstruction were randomized to receive either continuous ACB (n = 25) with 0.5% ropivacaine infusing at 2.5 ml/h or intermittent boluses (n = 25) of 15 ml of 0.5% ropivacaine every 6 h. Total morphine consumption 24 h following surgery was recorded in each group. RESULTS: Fifty subjects completed this study. The mean 24-h total morphine consumption in the intermittent group, [11.36 (6.82) mg], was significantly reduced compared with the continuous group, [23.40 (10.45) mg] (P < 0.001). The mean visual analogue scale (VAS) pain score at rest and on knee flexion was significantly reduced in the intermittent group at 4, 6, 8, and 12 h compared with the continuous group. CONCLUSION: Intermittent ACB allowed significantly reduced consumption of morphine for 24 h in the post-operative period compared with continuous ACB when identical doses of ropivacaine were used in each group.

Combined spinal-epidural for labor analgesia with low-dose bupi- vacaine but without any opioid in the spinal component: can we improve upon the traditional?

AIM: To compare the efficacy and safety of combined spinal-epidural (CSE, with the spinal component using low-dose heavy bupivacaine without opioid) with low-dose epidural analgesia in labor. METHODS: Sixty consenting adult parturients requesting epidural were randomly allocated to two equal groups to receive either low-dose epidural or CSE analgesia. The Epidural Group received 10ml of a mixture of 0.1% bupivacaine and 2 µg/ml fentanyl, followed by a 6 ml first bolus after 10 min if needed (not considered as a top-up). All patients received 8 ml/h continuous background infusion, with patient-controlled top-up bolus of 6 ml with a lock-out interval of 12 min. In the CSE Group, 0.5% (heavy) bupivacaine 2.5 mg was used to produce spinal block (without concomitant use of any opioid), followed by epidural continuous background infusion of 8 ml of 0.1% of bupivacaine and 2 µg/ml of fentanyl, with a similar top-up provision as in the Epidural Group. Primary outcome was total drug consumption during labor, corrected by the duration of labor (ml/h). RESULTS: Mean total drug consumption during labor was significantly less in the CSE group (9.69 ml/h) than in Epidural group (13.52 ml/h ; P < 0.00 1). CSE also led to significantly faster onset of analgesia and sensory block. There was no significant difference between the two groups with regard to all other variables. Maternal satisfaction was rated as 'excellent' by all subjects. CONCLUSIONS: CSE using low-dose heavy bupivacaine without opioid required less drug consumption produced faster onset of pain control and sensory block than low-dose epidural analgesia. There were no other significant inter-group differences.

Analgesic efficacy of pre-operative stellate ganglion block on postoperative pain relief: a randomised controlled trial.

We undertook a randomised, double-blind, placebo-controlled study to compare the analgesic efficacy of pre-operative stellate ganglion block on postoperative pain relief after upper limb orthopaedic surgery. Patients were administered a 3-ml injection during ultrasound-guided stellate ganglion block; 15 patients received lidocaine 2% and 15 patients received 0.9% saline. Following the block, all patients received standardised general anaesthesia. Postoperative analgesia included regular intravenous diclofenac, paracetamol and patient-controlled analgesia with tramadol for 24 h. Patients were observed at 0, 2, 4, 6, 8, 12 and 24 h after surgery for tramadol consumption, cardiovascular variables and visual analogue scale pain scores at rest and on movement. The mean (SD) hourly tramadol consumption was significantly reduced in the lidocaine group compared with the saline group at 4 h (8.0 (10.1) mg vs 28.0 (12.6) mg, respectively; p = 0.001), 6 h (5.3 (10.8) mg vs 17.3 (12.7) mg, respectively; p = 0.013) and 8 h (5.3 (11.8) mg vs 21.3 (9.1) mg, respectively; p = 0.001). The cumulative 24-h tramadol consumption was 97.3 (16.6) mg in the lidocaine group and 150.6 (26.0) mg in the saline group (p = 0.001). There were significant differences in the pain visual analogue scale at rest at two time points; at 4 h the median (IQR [range]) visual analogue scale scores were 4 (4-6 [2-8]) in the lidocaine group and 5 (4-6 [2-7]) in the saline group (p = 0.03), and at 6 h visual analogue scale scores were 3 (3-4 [3-6]) and 4 (4-6 [2-7]), respectively (p = 0.04). Pain visual analogue scale on movement was lower in the lidocaine group at all time intervals compared with the saline group, but this did not reach statistical significance. The present study has demonstrated a postoperative tramadol-sparing and analgesic effect of pre-operative stellate ganglion block in patients undergoing upper limb orthopaedic surgery under general anaesthesia.

The management of acute shortness of breath in young adults.

Shortness of breath (SOB), or dyspnoea, is a common presenting symptom in acute care, responsible for 8% of all 999 calls to the ambulance service and ranking as the third most common type of emergency call-(l). It may be associated with significant pathology, so prompt identification and appropriate management are therefore imperative. Although a formal diagnosis guides risk stratification, prognostication and treatment, it must not delay resuscitation. Rather, the management of an acutely short of breath (ASOB) patient must follow an algorithm incorporating simultaneous assessment and resuscitation. This article discusses both of these aspects in some detail, as well as key features in the history and the differential diagnosis, before concluding with some consideration of how the different operational environments in which such patients can present may affect their management.

Closed and open breathing circuit function in healthy volunteers during exercise at Mount Everest base camp (5300 m).

We present a randomised, controlled, crossover trial of the Caudwell Xtreme Everest (CXE) closed circuit breathing system vs an open circuit and ambient air control in six healthy, hypoxic volunteers at rest and exercise at Everest Base Camp, at 5300 m. Compared with control, arterial oxygen saturations were improved at rest with both circuits. There was no difference in the magnitude of this improvement as both circuits restored median (IQR [range]) saturation from 75%, (69.5-78.9 [68-80]%) to > 99.8% (p = 0.028). During exercise, the CXE closed circuit improved median (IQR [range]) saturation from a baseline of 70.8% (63.8-74.5 [57-76]%) to 98.8% (96.5-100 [95-100]%) vs the open circuit improvement to 87.5%, (84.1-88.6 [82-89]%; p = 0.028). These data demonstrate the inverse relationship between supply and demand with open circuits and suggest that ambulatory closed circuits may offer twin advantages of supplying higher inspired oxygen concentrations and/or economy of gas use for exercising hypoxic adults.

Study of the sensitising potential of various textile dyes using a biphasic murine local lymph node assay.

Disperse dyes, which are suitable for dyeing synthetic fibres, are responsible for the great majority of allergic contact dermatitis (ACD) cases to textile dyes. The aim of the present study was to investigate the sensitising potential of various disperse dyes using a biphasic protocol of the local lymph node assay (LLNA). Briefly, mice were shaved over a surface of approximately 2 cm(2) on their backs and treated using a "sensitisation-challenge protocol". The shaved surface was treated once daily on days 1-3 with 50 microl of the test solution. Animals remained untreated on days 4-14. On days 15-17, mice were treated with 25 microl of the test solution on the dorsum of both ears. Mice were killed on day 19 with deep CO(2) anaesthesia, the lymph nodes prepared and various end points, such as ear thickness, ear punch weight, lymph node weight, lymph node cell count and the proportion of various lymphocyte subpopulations, were determined by flow cytometry. The results were compared to control group treated with the vehicle alone. Our results showed that almost all of the tested textile dyes caused a significant increase in lymph node cell count and lymph node weight. We also observed an increase in ear thickness and ear punch weight in most of the concentrations tested for various textile dyes. We observed a decrease in CD4+ and CD8+ cells and an increase in CD19+, CD45+ and CD45+/1A+ cells in most of the cases, which is characteristic for allergens. The CD4+/CD69+ cells increased in only few experiments mainly with Disperse Blue 124 and Disperse Blue 106. Based on our results, the disperse dyes could be arranged in four groups on the basis of their sensitising potency in the following decreasing order (in parenthesis: lowest concentration causing a significant increase in lymph node cell number): group 1, strong: Disperse Blue 124 and Disperse Blue 106 (0.003%); group 2, moderate: Disperse Red 1 and Disperse Blue 1 (3%); group 3, weak: Disperse Orange 37 and Disperse Blue 35 (10%); and group 4, very weak: Disperse yellow 3 and Disperse Orange 3 (increase at 30% or no increase at 30%). In conclusion, our study shows that the biphasic LLNA protocol was proficient enough to study the sensitisation potential of tested textile dyes and provides data allowing to discriminate them according to their potency.

Awake tracheostomy in a child with respiratory distress due to retropharyngeal abscess.

Awake tracheostomy in a child with respiratory distress is an emergency life-saving procedure when risk of airway loss after induction of general anaesthesia is greater due to difficult anatomy. A 10-year-old boy presented three days after removal of a foreign body in the throat under general anaesthesia. Over the subsequent days, the patient had a progressively increasing visible swelling in the neck, stridor and respiratory distress. An urgent X-ray and computed tomography scan of the neck revealed a retropharyngeal abscess compressing the trachea. Due to anticipated difficulty in airway management under general anaesthesia, we decided to perform an awake tracheostomy. The child and the parents were counselled regarding steps of awake tracheostomy, as well as the benefits and possible risks associated with it. Topicalisation was achieved by administering glycopyrrolate, nebulisation with lidocaine 4%, and the skin was prepared with lidocaine 2% with 1:200,000 adrenaline. After the awake tracheostomy was successfully performed, general anaesthesia was induced and the retropharyngeal abscess was drained. Effective communication and building rapport is essential for safe awake tracheostomy in a child with respiratory distress when impending airway loss may occur at any moment.

Frailty is a better predictor than age for outcomes in geriatric patients with rectal cancer undergoing proctectomy.

BACKGROUND: Both frailty and older age are risk factors for adverse surgical outcomes. We hypothesized that frailty, regardless of patient age, is a predictor of poor postoperative outcome among patients with rectal cancer undergoing proctectomy. METHODS: Patients with primary rectal cancer undergoing proctectomy between 2012 to 2015 were identified in the database of the National Quality Improvement Program. The simplified, 5-item frailty index was grouped into 0, 1, 2, and ≥3. Outcomes were morbidity and 30-day mortality. RESULTS: This study involved 9,252 patients from the National Quality Improvement Program database. Increasingly frail patients had greater morbidity and mortality (P < .001). Logistic regression revealed that frailty was a predictor of morbidity (odds ratio = 6.7, P < .0001); in contrast, older age was not associated with morbidity when adjusting for frailty (odds ratio = 1.2, P = .14). Both older age and frailty were associated with greater mortality, with frailty (odds ratio = 20.8, P < .0001) more so than older age (odds ratio = 10.3, P < .0001). CONCLUSION: Frailty was more strongly associated with morbidity and mortality than older age in patients undergoing proctectomy. Surgical options can be expanded to older patients with the use of simplified, 5-item frailty index as a decision-making tool.

Evaluation of delay in time to adjuvant chemotherapy after HIPEC and its impact on oncological outcome in advanced epithelial ovarian cancer.

OBEJECTIVES: Optimal cytoreductive surgery (CRS), followed by adjuvant chemotherapy, is a major predictor of oncological outcome in patients with advanced epithelial ovarian carcinoma (EOC). It is not clear if a delayed start of adjuvant chemotherapy negatively impacts on the oncological outcome. METHODS: Prospective registry study on 75 patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Adjuvant chemotherapy was started within 42 days in 41 patients (55%), later on in 34 patients (45%). Multivariate analyses of preoperative factors were done on survival outcome. Outcomes were recurrence-free survival (RFS) and overall survival (OS). RESULTS: There was no difference in RFS after early introduction (median 35 months) vs. late introduction of chemotherapy (median 32 months), p = 0.17. Median OS in patients with late introduction of chemotherapy was 46 months and was not yet reached in early introduction group. CONCLUSIONS: In this exploratory study in a small group of women with advanced EOC, starting adjuvant chemotherapy more than 6 weeks after CRS and HIPEC did not deteriorate significantly RFS or OS. Well-designed clinical studies are still needed to evaluate the interplay of HIPEC and the point of time of postoperative adjuvant chemotherapy in this indication.

Human carbamoyl-phosphate synthetase: insight into N-acetylglutamate interaction and the functional effects of a common single nucleotide polymorphism.

Human carbamoyl-phosphate synthetase (hCPS) has evolved three features that allow it to remove excess, potentially neurotoxic ammonia via the urea cycle: inability to use glutamine as an alternative nitrogen donor; a K(m) for ammonia 100-fold lower than for CPSs that also use glutamine; and required allosteric activation by N-acetylglutamate (AGA), a sensor of excess amino acids. To determine the structural features of hCPS that allow its unique functioning, we have developed the first recombinant expression system for hCPS, utilizing Schizosaccharomyces pombe. Of several common single-nucleotide polymorphisms identified in the gene encoding hCPS, only the one resulting in substitution of threonine at position 1406 with asparagine has been linked to phenotypic effects. We have expressed and characterized both variants of hCPS. The asparagine polymorph, hCPS_N, consistently displayed inferior catalytic properties, but the K(m) and k(cat) values for overall and partial reactions varied only by a factor of 1.7 or less. We have designed and characterized an hCPS construction from which the N-terminal domain A is deleted. hCPS_DeltaA was competent to bind AGA, demonstrating that domain A does not contain the AGA binding site. Thus, the site at the C/D boundary previously identified by AGA analogue labelling appears to be the functionally significant initial binding site for AGA. However, hCPS_DeltaA was not able to fully assume the catalytically competent conformation, with specific activity of CP formation decreased 700-fold.

Cross cultural comparison of constipation profiles at tertiary care centers between India and USA.

BACKGROUND: Despite potential differences in patient perception of chronic constipation (CC) in geographically and culturally distinct regions, head-to-head studies comparing the clinical profile, constipation severity, impact on quality of life (QOL) and economic impact are lacking. METHODS: We conducted a cross-sectional cohort study of patients presenting with CC to tertiary care centers in the USA and India. Standardized instruments were used to assess constipation subtype, disease severity, disease-specific QOL, somatization, and psychiatric comorbidities. We used multivariable linear regression to determine the predictors of QOL and number of healthcare visits. KEY RESULTS: Sixty-six and 98 patients with CC were enrolled in the USA and India, respectively. Indian patients with CC had significantly more frequent bowel movements/week compared to their USA counterparts (Median 5 vs 3, P < .0001). The proportion of patients with Bristol stool form scale type 1 and 2 was significantly higher in the USA compared to India (65.5% vs 48%, P = .04). Higher depression score (P = .001), more severe constipation symptoms (P = .001) and site of the study being USA (P = .008) independently predicted worse QOL. Indian patients (P < .001) and worse QOL (P = .02) were independent predictors of number of healthcare visits in the last 12 months. CONCLUSIONS AND INFERENCES: Indian patients with CC have more frequent and softer bowel movements compared to those in the USA suggesting significant differences in perception of CC in different geographic and cultural settings. QOL and economic impact related to constipation varies with geographic/cultural setting irrespective of other clinical and psychosomatic features.