Core structure dependence of cycloreversion dynamics in diarylethene analogs.

Diarylperfluorocyclopentenes are a well-characterized class of molecular photoswitches that undergo reversible photocyclization. The efficiency of cycloreversion (<∼30%), in particular, is known to be limited by a competition with excited-state deactivation by internal conversion that is strongly impacted by the electron-withdrawing/donating character of pendant aryl groups. Here we present a first study to determine how varied structural motifs for the core bridge group impact excited-state dynamics that control cycloreversion quantum yields. Specifically, we compare photophysical behaviors of 3,3'-(perfluorocyclopent-1-ene-1,2-diyl)bis(2-methylbenzo[b]thiophene) with diarylethene derivatives possessing the same benzo[b]thiophene pendant group but with a rigid 1-methyl-1H-pyrrole-2,5-dione and a rigid/aromatic thieno[3,4-b]thiophene bridge (TT) core bridge group. We find that the flexible perfluorocyclopentene core undergoes cycloreversion 3-4× slower than the rigid core photoswitches (9 vs. 2-3 ps in acetonitrile, 25 vs. 5-6 ps in cyclohexane) despite comparable cycloreversion quantum yields. To distinguish effects induced by bridge vs. pendant groups, we also studied a series of photoswitches with the same thieno[3,4-b]thiophene bridging group, but with varied pendant groups including 2,5-dimethylthiophene and 2-(3,5-bis(trifluoromethyl)phenyl)-5-methylthiophene. Analysis of temperature-dependent excited-state lifetimes and cycloreversion quantum yields reveals that both the rates of nonreactive internal conversion and reactive cycloreversion increase with greater structural rigidity of the core. This difference is attributed to smaller energy barriers on the excited-state potential energy surface for both reactive and non-reactive deactivation from the 21A electronic state relative to the flexible perfluorocyclopentene switch, implying that a rigid core results in a net shallower excited-state potential energy surface.

Energy- and conformer-dependent excited-state relaxation of an E/Z photoswitchable thienyl-ethene.

Bis(bithienyl)-1,2-dicyanoethene (4TCE) is a photoswitch that operates via reversible E/Z photoisomerization following absorption of visible light. cis-to-trans photoisomerization of 4TCE requires excitation below 470 nm, is relatively inefficient (quantum yield < 5%) and occurs via the lowest-lying triplet. We present excitation-wavelength dependent (565-420 nm) transient absorption (TA) studies to probe the photophysics of cis-to-trans isomerization to identify sources of switching inefficiency. TA data reveals contributions from more than one switch conformer and relaxation cascades between multiple states. Fast (∼4 ps) and slow (∼40 ps) components of spectral dynamics observed at low excitation energies (>470 nm) are readily attributed to deactivation of two conformers; this assignment is supported by computed thermal populations and absorption strengths of two molecular geometries (PA and PB) characterized by roughly parallel dipoles for the thiophenes on opposite sides of the ethene bond. Only the PB conformer is found to contribute to triplet population and the switching of cis-4TCE: high-energy excitation (<470 nm) of PB involves direct excitation to S2, relaxation from which prepares an ISC-active S1 geometry (ISC QY 0.4-0.67, kISC∼ 1.6-2.6 × 10-9 s-1) that is the gateway to triplet population and isomerization. We ascribe low cis-to-trans isomerization yield to excitation of the nonreactive PA conformer (75-85% loss) as well as loses along the PB S2→ S1→ T1 cascade (10-20% loss). In contrast, electrocyclization is inhibited by the electronic character of the excited states, as well as a non-existent thermal population of a reactive "antiparallel" ring conformation.

A prospective study of evaluation of operative duration as a predictor of mortality in pediatric emergency surgery: Concept of 100 minutes laparotomy in resource-limited setting.

INTRODUCTION: Operative duration is an important but under-studied predictor of mortality in emergency laparotomies. AIMS AND OBJECTIVES: The primary objective of this study was to quantify the effect of duration of emergency laparotomy in children on mortality; and to identify a rough cut-off duration of laparotomy to serve as a guide so that a laparotomy can be planned to optimize pediatric surgical patient outcome. MATERIALS AND METHODS: This is a prospective study conducted in a government tertiary teaching institution over a period of 24 months. All children in the age group of 5-10 years presenting in the emergency department with Pediatric Risk of Mortality III score ≤8, undergoing emergency laparotomy in emergency operation theater, were included. OBSERVATIONS AND RESULTS: In all, 213 children were included in the study. The mean time from presentation to shifting to the operating room was 3.7 h. The mean operative duration was 108 min. The mean operative time in survived patients was 102 min as compared to 135 min in expired patients (P < 0.05). The 30-day in-hospital mortality rate was 17.4%. After application of binary logistic regression analysis, it was found that time to laparotomy and operative duration were significant risk factors (<0.05) predicting post-operative mortality. Kaplan-Meier survival curve showed a decrease at a mean weighted operative duration of approximately 100 min. Receiver operating characteristic curve analysis yielded operative duration of 123.5 min at which Youden's index maximized. CONCLUSION: This 100-min duration of laparotomy might appear a long duration but in casualty setup of a government hospital with limited resources, there are so many hurdles for optimal working that completion of an emergency laparotomy in children in 100 min can be considered a realistic target for improving post-operative outcome. At an operative duration of <123.50 min, mortality rates within acceptable limits can be achieved.

Advanced diagnostic genetic testing in inherited retinal disease: experience from a single tertiary referral centre in the UK National Health Service.

In 2013, as part of our genetic investigation of patients with inherited retinal disease, we utilized multigene panel testing of 105 genes known to cause retinal disease in our patient cohorts. This test was performed in a UK National Health Service (NHS) accredited laboratory. The results of all multigene panel tests requested between 1.4.13 and 31.8.14 were retrospectively reviewed. All patients had been previously seen at Moorfields Eye Hospital, London, UK and diagnosed with an inherited retinal dystrophy after clinical examination and detailed retinal imaging. The results were categorized into three groups: (i) Testing helped establish a certain molecular diagnosis in 45 out of 115 (39%). Variants in USH2A (n = 6) and RP1 (n = 4) were most common. (ii) Definitive conclusions could not be drawn from molecular testing alone in 13 out of 115 (11%) as either insufficient pathogenic variants were discovered or those identified were not consistent with the phenotype. (iii) Testing did not identify any pathogenic variants responsible for the phenotype in 57 out of 115 (50%). Multigene panel testing performed in an NHS setting has enabled a molecular diagnosis to be confidently made in 40% of cases. Novel variants accounted for 38% of all identified variants. Detailed retinal phenotyping helped the interpretation of specific variants. Additional care needs to be taken when assessing polymorphisms in genes that have been infrequently associated with disease, as historical techniques were not as rigorous as contemporary ones. Future iterations of sequencing are likely to offer higher sensitivity, testing a broader range of genes, more rapidly and at a reduced cost.

Androgen receptor and its correlation with estrogen and progesterone receptors, aimed for identification of cases for future anti-androgen therapy in endometrial cancers.

INTRODUCTION: The expression of androgen receptor (AR) is not commonly tested or studied in uterine cancers, unlike estrogen receptor (ER) and progesterone receptor (PR) which are positive in most endometrial carcinomas. In this series, we evaluated the expression of AR and its comparison to ER and PR in different types of endometrial cancers and have reviewed the literature. MATERIALS AND METHODS: The status of AR, ER, and PR expression were evaluated in 71 cases which were categorized into endometrial endometrioid cancer (EEC), non-endometrioid endometrial cancers (NEEC), and metastatic carcinomas of endometrium. Expression of the receptors were compared to each other as well as to mismatch repair proteins (MMR), p53, and body mass index (BMI) using Fisher's Exact test in the StatPlus software. RESULTS: In EECs, the positivity was 97% for all the three receptors. In NEEC, positivity rates were 68%, 48%, and 35% for AR, ER, and PR respectively. In Metastatic carcinomas, AR and ER positivity was seen in 100% while PR was positive in 75% of the cases. In all cancers, the rates were 17% (11/66) for MMR loss, 57% (30/53) for p53 aberrant expression, and 76% (54/71) for the patients with BMI of ≥ 25 (kg/m2). CONCLUSION: AR is expressed in a high percentage of endometrial cancers. Its significance is more evident in high-grade NEEC where ER and PR may not be expressed. These findings warrant further evaluation of AR expression and candidacy of this pathway as a potential therapeutic target in endometrial cancers.

Albumin-induced epithelial mesenchymal transformation.

BACKGROUND: Progressive chronic kidney disease is often associated with albuminuria and renal fibrosis linked to the accumulation of myofibroblasts producing extracellular matrix. Renal myofibroblasts are derived from a number of cells including tubular epithelial cells (TECs) through epithelial mesenchymal transformation (EMT). This study explores the hypothesis that exposure of TECs to albumin induces EMT. METHODS: Normal rat TECs (NRK52E) were exposed in culture to de-lipidated bovine serum albumin (dBSA; 10 mg/ml) for 2, 4 and 6 days. Binding/uptake of fluoresceined albumin by PTCs was evaluated. Transformation into myofibroblasts was assessed by light and electron microscopy, immunofluorescence and Western blotting for α-smooth muscle actin (α-SMA), E-cadherin and transforming growth factor-ß1 (TGF-ß1). We also investigated the expression of fibroblast-specific protein-1 (FSP-1) and collagens I, III and IV. TGF-ß1 biological activity, mRNA and protein were measured. A neutralising anti-TGF-ß1 antibody was used to analyse the role of TGF-ß1 in albumin-induced EMT. RESULTS: Exposure of TECs to dBSA led to binding/uptake of albumin as well as fibroblastic morphological changes. Incubation of TECs with dBSA caused a reduction of TEC marker E-cadherin (ANOVA p = 0.0002) and de novo expression of fibroblast markers α-SMA and FSP-1 (ANOVA p = 0.0001) in a time-dependent manner. It also increased expression and activity of TGF-ß1. Neutralisation of TGF-ß1 significantly reduced EMT (p < 0.01). CONCLUSION: This study demonstrates that in vitro, albumin induces the transformation of TECs into cells with myofibroblast characteristics; a process that may be TGF-ß1 dependent.

Effects of palliative radiation therapy on nonsplenic hemangiosarcoma in dogs.

Medical records for 20 dogs with histologically confirmed nonsplenic hemangiosarcomas treated with palliative radiation therapy were reviewed to evaluate factors influencing tumor response and survival time. The Kaplan-Meier median survival time of dogs that received palliative radiation therapy was 95 days (range 6 to 500 days). Subjective reduction in tumor size was seen in 14 dogs, with four complete responses. Tumor location was a significant univariate prognostic factor for survival, and dogs with retroperitoneal masses had longer survival times.

Cytodiagnosis of yolk sac tumor.

To analyze cytomorphologic features of yolk sac tumors of childhood. Four cases of pediatric yolk sac tumor (YST), diagnosed by fine needle aspiration cytology were reviewed (1998-2002). Age of patients ranged from 1(1/2) to 5 years. Three cases presented clinically with an intra-abdominal mass while one case presented with a testicular mass. Fine needle aspirates had been obtained directly as well as under radiologic (USG/CT) guidance. Smears were stained with H & E and Papanicolaou stain. In all cases values of serum alpha-fetoprotein and hCG were available preoperatively. Histopathologic diagnosis was correlated with cytologic findings in all the cases. Cytologic examination showed richly cellular smears with a combination of morphological patterns. Characteristically, tumor cells were arranged in papillary groups, tight cell clusters and formed acinar structures. Cells showed enlarged, moderately pleomorphic, hyperchromatic nuclei and moderate amount of cytoplasm, some of which displayed cytoplasmic vacuolation, displacing the nuclei eccentrically. Preoperatively, serum alpha-fetoprotein level was raised in all cases. Histopathology confirmed the cytologic diagnosis. Yolk sac tumor is common among the germ cell tumors of pediatric age group which presents a spectrum of cytomorphologic features having important differences with other germ cell neoplasm, e.g. embryonal carcinoma. Clinicoradiologic features and tumor markers are additionally helpful for an accurate cytologic diagnosis.

Gastroesophageal reflux in infants and children.

Seventy-five infants and children presenting during the period December 1984 to December, 1987 with the clinical features of vomiting, failure to thrive, chronic cough, recurrent pneumonia and atypical asthma were evaluated for gastroesophageal reflux by standard barium esophagram. Fifty six cases (74.7%) and as many as 80% of the infants studied had gastroesophageal reflux; Grade II reflux was seen in 12 cases, Grade III in 30 and Grade IV in 14 cases. The patients with gastroesophageal reflux were put on medical treatment. All the patients had subjective improvement after 6 weeks to 6 months of conservative treatment and none of them developed further complications of gastroesophageal reflux during a follow-up period varying from two months to fifteen months. Anti-reflux surgery was not considered owing to the subjective improvement in all the patients on conservative treatment. We conclude that gastroesophageal reflux is very common in infants and children and urge the need to evaluate the patients presenting with the symptoms suggesting gastroesophageal reflux by barium esophagram; conservative treatment is the mainstay in the management of these children.

Peri-anesthetic management of tracheo-esophageal fistula.

During a 3-year period 11 neonates underwent general anesthesia for primary repair of tracheo-esophageal fistula (TEF). The age ranged from 1-10 days. Out of these patients, 8 (72.7%) had atresia of the esophagus with a blind upper pouch and lower segment communicating with a trachea. A total of 7 patients (63.6%) had aspiration pneumonitis pre-operatively. Intubation was difficult in 3 (27.3%). There was no intraoperative mortality. However, the incidence of post-operative mortality was 27.3% (3 cases). The cause of death in all these cases was severe non-resolving pneumonia.

Ceramic-on-ceramic bearings in young patients: outcomes and activity levels at minimum ten-year follow-up.

We report the clinical and radiological outcomes of a series of contemporary cementless ceramic-on-ceramic total hip replacements (THRs) at ten years in patients aged ≤ 55 years of age. Pre- and post-operative activity levels are described. A total of 120 consecutive ceramic cementless THRs were performed at a single centre in 110 patients from 1997 to 1999. The mean age of the patients at operation was 45 years (20 to 55). At ten years, four patients had died and six were lost to follow-up, comprising ten hips. The mean post-operative Harris hip score was 94.7 (55 to 100). Radiological analysis was undertaken in 90 available THRs of the surviving 106 hips at final review: all had evidence of stable bony ingrowth, with no cases of osteolysis. Wear was undetectable. There were four revisions. The survival for both components with revision for any cause as an endpoint was 96.5% (95% confidence interval 94.5 to 98.7). The mean modified University of California, Los Angeles activity level rose from a mean of 6.4 (4 to 10) pre-operatively to 9.0 (6 to 10) at the ten-year post-operative period. Alumina ceramic-on-ceramic bearings in cementless primary THR in this series have resulted in good clinical and radiological outcomes with undetectable rates of wear and excellent function in the demanding younger patient group at ten years.

Diagnostic value of ultrasonography in evaluation and management of acute abdominal conditions in the paediatric age group.

BACKGROUND: The aims of this study have been elaborated below: (1) to enumerate the common causes of acute abdominal emergencies by ultrasonography in paediatric patients; (2) to establish the diagnostic efficacy of ultrasonography in evaluation of acute abdominal conditions in children and to illustrate the associated ultrasonographic findings; (3) and, to discuss the role of ultrasonography in guiding the mode of intervention in these cases. PATIENTS AND METHODS: This prospective study of ultrasonographic examination in 146 paediatric patients presenting with acute onset abdominal pain at the emergency/paediatric outpatient department section of Jawaharlal Nehru Medical College & Hospital, Aligarh, between June 2006 and December 2007, using 3.75 MHz and 8 MHz transducers of the ADARA (Siemens) machine. RESULTS: Common causes of acute abdominal emergencies in pediatric patients as noted on ultrasonography included nonspecific pain (28%), abdominal abscess (21%), acute appendicitis (7%) and intussusception (7%). Ultrasonography was diagnostic in 45.2% cases and supportive in 12.3% of the cases. As for as the final outcome, ultrasonography prevented surgery in almost 20% cases and laparotomy was avoided in 7% of the patients as ultrasound guided interventions in the form of abscess aspiration were carried out. CONCLUSION: Ultrasonography evaluation of children with acute abdominal pain, helps in making significant changes in the management plan of the patients, and also reveals various clinically unsuspected diseases.

Mixing and matching causing taper wear: corrosion associated with pseudotumour formation.

We report a case of a male patient presenting with bilateral painful but apparently well-positioned and -fixed large-diameter metal-on-metal hip replacements four years post-operatively. Multiple imaging modes revealed a thick-walled, cystic expansile mass in communication with the hip joint (a pseudotumour). Implant retrieval analysis and tissue culture eliminated high bearing wear or infection as causes for the soft-tissue reaction, but noted marked corrosion of the modular neck taper adaptor and corrosion products in the tissues. Therefore, we believe corrosion products from the taper caused by mismatch of the implant components led to pseudotumour formation requiring revision.

Warfarin management in patients on continuous anticoagulation therapy undergoing total knee replacement.

We evaluated the safety and efficacy of total knee replacement in patients receiving continuous warfarin therapy. We identified 24 consecutive patients receiving long-term warfarin therapy who underwent total knee replacement between 2006 and 2008 and compared them with a group of age- and gender-matched patients not on long-term anticoagulation. Primary observations were changes in haemoglobin, transfusion rates and complications. Secondary observations were fluctuations in the international normalised ratio (INR) and post-operative range of movement. There was no significant difference between the two groups in pre- or post-operative haemoglobin, incidence of transfusion or incidence of post-operative complications. There were no surgical delays due to a high INR level. The mean change in INR during the peri-operative phase was minimal (mean 0.4; SD 0.7). There was no significant difference in the range of movement between the two groups after day two post-operatively. Current American College of Chest Physicians guidelines recommend bridging therapy for high-risk patients receiving oral anticoagulation and undergoing major orthopaedic procedures. We have shown that a safe alternative is to continue the steady-state warfarin peri-operatively in patients on long-term anticoagulation requiring total knee replacement.