Trifluoroethylation and Pentafluoropropylation of C(sp3)-H Bonds.

Polyfluorinated substituents often enhance effectiveness, improve the stability within metabolic processes, and boost the lipophilicity of biologically active compounds. However, methods for their introduction into aliphatic carbon chains remain very limited. A potentially general route to integrate the fluorinated scaffolds into organic molecules involves insertion of fluorine-containing carbenes into C(sp3)-H bonds. The electron-withdrawing characteristics of perfluoroalkyl groups enhances the reactivity of these carbenes which should enable the functionalization of unactivated C(sp3)-H bonds. Curiously, it appears that use of perfluoroalkyl-containing carbenes in alkane C-H functionalization is exceedingly rare. This concept describes photolysis, enzymatic catalysis, and transition metal catalysis as three primary approaches to C(sp3)-H functionalization by trifluoromethylcarbene and its homologues.

Comparative evaluation of bite force in patients treated for unilateral mandibular condylar fractures by open and closed methods.

BACKGROUND/AIM: Condylar fractures account for a large proportion (20% to 52%) of mandibular injuries. The goal of treating these fractures is to restore the occlusion, thereby re-establishing the masticatory function as close as possible to the patient's pre-trauma state. The aim of this study was to compare the bite forces following unilateral condylar fractures treated by open reduction and internal fixation (ORIF) with those managed by the closed method. METHOD: Patients with unilateral mandibular condylar fractures were divided into two groups (n = 20) using a simple randomization method. Patients in group I were treated by open reduction and internal fixation (ORIF) using titanium miniplates and screws. Patients in group II were treated by the closed method with inter-maxillary fixation. Patients in both groups were evaluated pre-operatively and then post-operatively at one week, one month and three months for maximum bite force achieved at the central incisor, premolar and molar regions. RESULTS: Pre-operative bite forces on the unaffected site were significantly higher than the affected site in both groups, whereas no significant difference was observed in bite forces between the unaffected and affected sites in both groups post-operatively. The bite forces achieved at both the unaffected and affected sites in the ORIF group were significantly higher than in the closed group. CONCLUSION: Maximum bite forces differed significantly when the treatment was done with the open method, and the patients treated with the open method needed less time to achieve the maximum bite forces, thereby making an earlier return to function.

Extended bipolar left ventricular pacing as a possible therapy for late electrical storm induced by cardiac resynchronization therapy.

Although cardiac resynchronization therapy (CRT) has become a well-established treatment option for patients with drug-refractory severe systolic heart failure, there has been some evidence of adverse proarrhythmic events. We report a case of a patient with ischemic cardiomyopathy who underwent CRT with a defibrillator for primary prevention of sudden cardiac death. Two years after the implantation, the patient presented with electrical storm, which was completely terminated by modifying the left ventricular (LV) pacing configuration from true to extended bipolar LV pacing. We discuss the possible pathophysiologic mechanisms of this phenomenon through a brief review of the literature on CRT-induced proarrhythmia.

Ventricular stimulus site influences dynamic dispersion of repolarization in the intact human heart.

The spatial variation in restitution properties in relation to varying stimulus site is poorly defined. This study aimed to investigate the effect of varying stimulus site on apicobasal and transmural activation time (AT), action potential duration (APD) and repolarization time (RT) during restitution studies in the intact human heart. Ten patients with structurally normal hearts, undergoing clinical electrophysiology studies, were enrolled. Decapolar catheters were placed apex to base in the endocardial right ventricle (RVendo) and left ventricle (LVendo), and an LV branch of the coronary sinus (LVepi) for transmural recording. S1-S2 restitution protocols were performed pacing RVendo apex, LVendo base, and LVepi base. Overall, 725 restitution curves were analyzed, 74% of slopes had a maximum slope of activation recovery interval (ARI) restitution (Smax) > 1 (P < 0.001); mean Smax = 1.76. APD was shorter in the LVepi compared with LVendo, regardless of pacing site (30-ms difference during RVendo pacing, 25-ms during LVendo, and 48-ms during LVepi; 50th quantile, P < 0.01). Basal LVepi pacing resulted in a significant transmural gradient of RT (77 ms, 50th quantile: P < 0.01), due to loss of negative transmural AT-APD coupling (mean slope 0.63 ± 0.3). No significant transmural gradient in RT was demonstrated during endocardial RV or LV pacing, with preserved negative transmural AT-APD coupling (mean slope -1.36 ± 1.9 and -0.71 ± 0.4, respectively). Steep ARI restitution slopes predominate in the normal ventricle and dynamic ARI; RT gradients exist that are modulated by the site of activation. Epicardial stimulation to initiate ventricular activation promotes significant transmural gradients of repolarization that could be proarrhythmic.

Study of fluorescence interaction and conformational changes of bovine serum albumin with histamine H1 -receptor--drug epinastine hydrochloride by spectroscopic and time-resolved fluorescence methods.

The fluorescence, ultraviolet (UV) absorption, time resolved techniques, circular dichroism (CD), and infrared spectral methods were explored as tools to investigate the interaction between histamine H1 drug, epinastine hydrochloride (EPN), and bovine serum albumin (BSA) under simulated physiological conditions. The experimental results showed that the quenching of the BSA by EPN was static quenching mechanism and also confirmed by lifetime measurements. The value of n close to unity indicated that one molecule of EPN was bound to protein molecule. The binding constants (K) at three different temperatures were calculated (7.1 × 10(4), 5.5 × 10(4), and 3.9 × 10(4) M(-1)). Based on the thermodynamic parameters (ΔH(0), ΔG(0), and ΔS(0)), the nature of binding forces operating between drug and protein was proposed. The site of binding of EPN in the protein was proposed to be Sudlow's site I based on displacement experiments using site markers viz, warfarin, ibuprofen, and digitoxin. Based on the Förster's theory of non-radiation energy transfer, the binding average distance, r between the donor (BSA) and acceptor (EPN) was evaluated and found to be 4.48 nm. The UV-visible, synchronous fluorescence, CD, and three-dimensional fluorescence spectral results revealed the changes in secondary structure of the protein upon its interaction with EPN.

Central analgesic activity of the aqueous and ethanolic extracts of the leaves of Albizia lebbeck: role of the GABAergic and serotonergic pathways.

Albizia lebbeck Benth. is extensively used in Indian traditional medicine for treating several painful and inflammatory disorders. The possible central analgesic activity and the underlying mechanism of action of the aqueous (AE) and ethanolic extracts (EE) of the leaves of A. lebbeck were investigated in Wistar rats using Eddy's hot plate and the tail flick tests. In order to investigate the underlying mechanism of action, rats were pretreated with naloxone, bicuculline or methysergide and then were administered a per os (p.o.) dose of AE or EE. AE and EE caused a significant (p<0.05) elevation in the mean basal reaction time in the hot plate method and an increase in the latency time in the tail flick method. In rats pretreated with bicuculline and methysergide, a significant (p<0.05) reduction in the analgesic activity was observed in comparison to AE and EE. Thus, AE and EE exhibited significant central analgesic activity and act possibly via the GABAergic and serotonergic pathways. The flavonoids and saponins found in the leaves could be responsible for the observed effect.

Hoffa's fracture with ipsilateral fibular fracture in a 16-year-old girl: An approach to a rare injury.

Hoffa's fracture is an uncommon fracture of the femoral condyle with coronal orientation of the fracture line. The mechanism of injury in pediatric Hoffa's fracture is road traffic accident, sports injury, and trivial injury. Clinical examination and proper imaging is important for diagnosis of pediatric Hoffa's fracture because of high chances of missing these injuries which can lead to nonunion and malunion at the fracture site. Open reduction and anatomical reduction of intraarticular fragment is the gold standard treatment of these fractures. We present a rare case of Hoffa's fracture in a 16-year-old girl with asso ciated ipsilateral fibular fracture.

Lingual versus buccal mucosa graft urethroplasty for anterior urethral stricture: a prospective comparative analysis.

OBJECTIVE: To compare lingual and buccal mucosa graft urethroplasty for anterior urethral stricture with respect to intraoperative, postoperative parameters and urethroplasty outcome. METHODS: From January 2011 to December 2011, a total of 30 patients with anterior urethral stricture whereas group 2 underwent dorsal onlay buccal mucosa graft urethroplasty. Patients were evaluated for postoperative, tongue protrusion, oral opening, and difficulty in speech and swallowing pain score. Surgical outcome was evaluated with pre- and postoperative work-up involving retrograde urethrogram, uroflow and urethroscopy. RESULTS: Mean age, stricture length and overall pain score were comparable in two groups. All the patients were mostly pain free by postoperative day 7. Group 1 patients had significant difficulty in speech and delayed return to normal diet as compared with group 2. The group 2 patients had a significant reduction in oral opening for the first week after surgery. In group 1, approximately 20% patients (with bilateral lingual grafts and stricture length >7 cm) complained of a change in speech character with restricted tongue movement in the long term, whereas there was no significant long-term morbidity in group 2. At mean follow up of 14.5 months, urethroplasty outcome was comparable in the two groups with one failure in group 1, and two failures in group 2. CONCLUSION: Lingual mucosa graft urethroplasty provides outcomes equivalent to those of buccal mucosa graft urethroplasty. Postoperative morbidity and long-term change in speech make it a second choice for strictures >7 cm, only for cases where buccal mucosa graft is unavailable.

Formulation and development of taste masked fast-disintegrating tablets (FDTs) of Chlorpheniramine maleate using ion-exchange resins.

CONTEXT: Masking of bitter taste of drug for better patient compliance. OBJECTIVE: The objective of this research was to mask the bitter taste of Chlorpheniramine maleate using cation exchange resins. MATERIALS AND METHODS: Different cation exchange resins were used for taste masking. The drug resin complexes (DRC) were prepared by batch process. Complexes of ion-exchange resin and Chlorpheniramine maleate were prepared by taking drug: resin ratios 1:1, 1:2, 1:3 and 1:4 (w/w). The optimum drug:resin ratio and the time required for maximum complexation was determined. The drug resinates were evaluated for the drug content, taste, drug release, FTIR, DSC and X-ray diffraction (PXRD). RESULTS AND DISCUSSION: The X-ray diffraction study confirmed the monomolecularity of entrapped drug in the resin beads. The taste evaluation depicted the successful taste masking of Chlorpheniramine maleate with DRCs. Fast disintegrating tablets (FDTs) were developed depending upon percent complexation, release study at salivary and gastric pH, taste evaluation; Chlorpheniramine maleate: Indion-234 complex of ratio 1:2 was used to develop and formulate FDTs. The drug release of 94.77% in 30 min was observed from FDTs. CONCLUSION: The Effective taste masking can be obtained from DRC that can be formulated as FDTs for better patient compliance.

Changing Trends in the Pattern of Maxillofacial Injuries in Helmeted Motorcycle Accident Patients when Compared to Non-helmeted Motorcycle Accident Patients.

Aim: Motorcycle accidents are the most predominant type of road traffic injuries in India. This prospective study aimed to evaluate the patterns of maxillofacial injuries in the three types of helmeted and non-helmeted individuals. Materials and Methods: All the patients reporting to the maxillofacial trauma unit of Sanjay Gandhi hospital with maxillofacial injuries were considered. The patients were analyzed for helmet wearing status, type of helmet worn-full-face, open-face and half-helmet, strap and visor fixation status, fit of the helmet, ownership of the helmet, helmet standardization, obeying traffic rules, alcohol consumption status, speed of the vehicle, volume of the engine, licensure of the driver, hard- and soft-tissue maxillofacial injuries were recorded. Results: A total of 741 patients participated in the study for a period of 10 months, majority being males and of a mean age of 31 years. Most common injuries to the face in the open- and half-helmet group were lacerations of the chin and mandibular fractures. Patients who wore ISI standard full-face helmets with strap and visor fixed experienced least injuries to the face. Conclusion: This study concluded that out of the three commonly used helmets, half-helmets provided the least protection against maxillofacial injuries during a crash, followed by the open-face helmets. The highest protection was provided by the full-face helmets with ISI standardization when secured properly with strap and visor.

A 33-Year-Old Woman With Breathing Difficulty, Inspiratory Wheeze, and Hemoptysis.

CASE PRESENTATION: A 33-year-old teacher from Ghana with no medical comorbidities and no relevant family history came to our pulmonology department with progressive difficulty in breathing, wheezing, and stridor for 6 months. Similar episodes had been treated previously as bronchial asthma. She was being treated with high-dose inhaled corticosteroids and bronchodilators but had no relief. The patient also described two episodes of large quantities of hemoptysis (> 150 mL) in the previous week. A general physical examination revealed a tachypneic young woman with an audible inspiratory wheeze. Her BP was 128/80 mm Hg; pulse, 90 beats/min; and respiratory rate, 32 breaths/min. There was a hard, minimally tender, nodular swelling of 3 × 3 cm in the midline neck felt just below the cricoid cartilage, moving with deglutition and protrusion of the tongue, with no retrosternal extension. There was no cervical or axillary lymphadenopathy. Laryngeal crepitus was present.

Basilar artery stroke in Crohn's disease treated with endovascular thromboembolectomy.

We describe a girl in middle childhood with newly diagnosed Crohn's disease, who presented with seizures and altered mental status. MRI showed an abnormal vascular signal at the basilar artery, but no evidence of acute ischaemia. Her weakness worsened over the next 8 hours to dense quadriplegia. CT angiography of the brain, approximately 24 hours after the initial onset of symptoms, identified an acute basilar artery occlusion with infarction. She received endovascular thromboembolectomy emergently. She showed significant improvement over 8-month period from quadriplegia to walking unassisted. This case highlights the importance of recognising stroke in patients with inflammatory bowel disease and the need for emergent radiological assessment and potential intervention.

Response of focal refractory status epilepticus to lacosamide in an infant.

Status epilepticus (SE) is a life-threatening medical emergency which is frequently encountered in the critical care setting and can be refractory to treatment. Refractory status epilepticus (RSE) is defined as SE that has failed to respond to adequately used first-line and second-line antiepileptic medications. Super refractory status epilepticus is defined as SE that persists for 24 hours or more after the use of an anaesthetic agent or recurs after its withdrawal.If SE persists beyond a period of 7 days it is referred to as prolonged, refractory status epilepticus (PRSE). There are limited data guiding treatment of RSE in the paediatric population.Lacosamide (LCM) is licensed as an adjunctive treatment for partial-onset seizures. Evidence for the efficacy of LCM in paediatric SE is scarce. This case report may suggest a synergistic effect of LCM on slow-activation sodium channels in conjunction with medications such as phenytoin that causes fast inactivation of sodium channels. The dual fast and slow inactivation of sodium channels may enhance the effectiveness in treatment of RSE. This is the first case report of PRSE in an infant, successfully treated with LCM. A brief review of literature is also a part of this report.

Emphysematous pyelonephritis: tertiary care center experience in management and review of the literature.

INTRODUCTION: In recent years there have been changes in management modality and a lower mortality with conservative management. We analyzed the result of emphysematous pyelonephritis (EPN) management by a review of the literature. MATERIAL AND METHODS: We made a retrospective study for the period from August 2005 to July 2009. Patients were evaluated by CT and subclassified based on CT. The patients managed in different modalities and their outcomes were compared. RESULTS: A total of 28 patients were admitted with the diagnosis of EPN. The age range was 22-70 years. Five patients were managed conservatively, 17 patients underwent minimally invasive modalities (double J stent, pigtail drainage). Open drainage of the abscess was conducted in 2 patients, and 4 patients required emergency nephrectomy. Emergency nephrectomy is associated with a high mortality (75%). CONCLUSIONS: In the majority of cases, EPN was successfully treated by resuscitation and minimally invasive modalities. Percutaneous drainage should be part of the initial management strategy. This strategy is associated with a lower mortality than emergency nephrectomy.

Illustration of the current practice and outcome comparison of early versus late tracheostomy after pediatric ECMO.

OBJECTIVE: Pediatric extracorporeal membrane oxygenation typically necessitates protracted ventilator support, yet not much is known about the use of tracheostomy in the pediatric subpopulation. The study was designed with an objective to quantify the prevalence of tracheostomy in children with respiratory/cardiac failure requiring extracorporeal membrane oxygenation and to compare outcomes for patients undergoing early, late, and no tracheostomy. METHODS: Data of patients <18 years of age who underwent extracorporeal membrane oxygenation for respiratory/cardiac failure between 2009 and 2015 were obtained from the Virtual Pediatric Systems (VPS, LLC) Database. Patients who underwent post-operative cardiac ECMO were excluded. Early versus late tracheostomy was defined as ⩽21 or >21 days after intensive care unit admission. RESULTS: Data were analyzed for 2127 patients meeting inclusion and exclusion criteria. Five percent (107/2127) underwent a tracheostomy. Of these, 28% (30/107) underwent early and 72% (77/107) late tracheostomy. A higher mortality was found in the no tracheostomy group (41.3%) compared to early (13.3%) and late tracheostomy (14.3%) groups. Late tracheostomy was associated with 2.4 times the expected intensive care unit length of stay and 1.87 times the expected ventilator days as compared to patients with no tracheostomy. Early tracheostomy was associated with a shorter intensive care unit length of stay (p value < 0.001) and ventilator days (p value = 0.04) compared to late tracheostomy and no difference with the no tracheostomy group. CONCLUSIONS: Late tracheostomy (>21 days) is associated with worse outcomes in the cohort of children who underwent Pediatric extracorporeal membrane oxygenation compared to patients who did not undergo tracheostomy. Early tracheostomy is associated with shorter intensive care unit stay and ventilator duration when compared to late tracheostomy.

Multicenter Study of Dynamic High-Density Functional Substrate Mapping Improves Identification of Substrate Targets for Ischemic Ventricular Tachycardia Ablation.

OBJECTIVES: The goal of this study was to evaluate the role of dynamic substrate changes in facilitating conduction delay and re-entry in ventricular tachycardia (VT) circuits. BACKGROUND: The presence of dynamic substrate changes facilitate functional block and re-entry in VT but are rarely studied as part of clinical VT mapping. METHODS: Thirty patients (age 67 ± 9 years; 27 male subjects) underwent ablation. Mapping was performed with the Advisor HD Grid multipolar catheter. A bipolar voltage map was obtained during sinus rhythm (SR) and right ventricular sense protocol (SP) single extra pacing. SR and SP maps of late potentials (LP) and local abnormal ventricular activity (LAVA) were made and compared with critical sites for ablation, defined as sites of best entrainment or pace mapping. Ablation was then performed to critical sites, and LP/LAVA identified by the SP. RESULTS: At a median follow-up of 12 months, 90% of patients were free from antitachycardia pacing (ATP) or implantable cardioverter-defibrillator shocks. SP pacing resulted in a larger area of LP identified for ablation (19.3 mm2 vs. 6.4 mm2) during SR mapping (p = 0.001), with a sensitivity of 87% and a specificity of 96%, compared with 78% and 65%, respectively, in SR. CONCLUSIONS: LP and LAVA observed during the SP were able to identify regions critical for ablation in VT with a greater accuracy than SR mapping. This may improve substrate characterization in VT ablation. The combination of ablation to critical sites and SP-derived LP/LAVA requires further assessment in a randomized comparator study.

Congenital urethrovaginal fistula with imperforate hymen: a first case report.

BACKGROUND: Congenital urethrovaginal fistulas are rare, and all five reported cases have been associated with urogenital abnormalities. We describe a case of congenital urethrovaginal fistula with an imperforate hymen and no other urogenital abnormalities. CASE: A 25-year-old female sought medical advice regarding cyclical hematuria, dyspareunia, and infertility of four years' duration. Investigations disclosed a urethrovaginal fistula with an imperforate hymen. The patient was successfully treated with excision of the hymen and closure of the urethrovaginal fistula. CONCLUSION: In this instance, the diagnosis of congenital urethrovaginal fistula was delayed until adulthood because the presence of urinary incontinence, the usual presentation of a urethrovaginal fistula, was concealed by the imperforate hymen. We could find no previously reported case of urethrovaginal fistula with imperforate hymen.

Segmentation of Intra-Retinal Cysts From Optical Coherence Tomography Images Using a Fully Convolutional Neural Network Model.

Optical coherence tomography (OCT) is an imaging modality that is used extensively for ophthalmic diagnosis, near-histological visualization, and quantification of retinal abnormalities such as cysts, exudates, retinal layer disorganization, etc. Intra-retinal cysts (IRCs) occur in several macular disorders such as, diabetic macular edema, retinal vascular disorders, age-related macular degeneration, and inflammatory disorders. Automated segmentation of IRCs poses challenges owing to variations in the acquisition system scan intensities, speckle noise, and imaging artifacts. Several segmentation methods have been proposed in the literature for IRC segmentation on vendor-specific OCT images that lack generalizability across imaging systems. In this paper, we propose a fully convolutional network (FCN) model for vendor-independent IRC segmentation. The proposed method counteracts image noise variabilities and trains FCN models on OCT sub-images from the OPTIMA cyst segmentation challenge dataset (with four different vendor-specific images, namely, Cirrus, Nidek, Spectralis, and Topcon). Further, optimal data augmentation and model hyperparametrization are shown to prevent over-fitting for IRC area segmentation. The proposed method is evaluated on the test dataset with a recall/precision rate of 0.66/0.79 across imaging vendors. The Dice correlation coefficient of the proposed method outperforms that of the published algorithms in the OPTIMA cyst segmentation challenge with a Dice rate of 0.71 across the vendors.

Deep Learning Based Sub-Retinal Fluid Segmentation in Central Serous Chorioretinopathy Optical Coherence Tomography Scans.

Development of an automated sub-retinal fluid segmentation technique from optical coherence tomography (OCT) scans is faced with challenges such as noise and motion artifacts present in OCT images, variation in size, shape and location of fluid pockets within the retina. The ability of a fully convolutional neural network to automatically learn significant low level features to differentiate subtle spatial variations makes it suitable for retinal fluid segmentation task. Hence, a fully convolutional neural network has been proposed in this work for the automatic segmentation of sub-retinal fluid in OCT scans of central serous chorioretinopathy (CSC) pathology. The proposed method has been evaluated on a dataset of 15 OCT volumes and an average Dice rate, Precision and Recall of 0.91, 0.93 and 0.89 respectively has been achieved over the test set.