Synthesis, biological evaluation, and molecular docking study of some new rohitukine analogs as protein tyrosine phosphatase 1B inhibitors.

Rohitukine (RH) was extracted from the stem bark of Dysoxylum binectariferum Hook. It was derivatized to different arylsulphanmides by treating with the corresponding aryl sulphonyl chlorides. These derivatives were tested in-vitro on protein tyrosine phosphatase 1B (PTP1B) inhibition. Among these the active compounds K2, K3, K5, and K8 significantly inhibited the PTP1B by 51.3%, 65.6%, 71.9%, and 55.9% respectively at 10 µg/ml, the results were also supported by in-silico docking experiments. The most potent compound K5 was analyzed for antidiabetic and antidyslipidemic activity in vivo. It showed a marked reduction in blood glucose level (random and fasting) and serum insulin level in db/db mice. It improved glucose intolerance as ascertained by the oral glucose tolerance test (OGTT). These NCEs (New Chemical Entities) also lowered cholesterol and triglyceride profiles while improved high-density lipoprotein cholesterol in db/db mice. The K5 was further evaluated for antiadipogenic activity on MDI (Methylisobutylxanthine, dexamethasone, and insulin)-induced adipogenesis. where it significantly inhibited MDI-induced adipogenesis in 3 T3-L1 preadipocytes, at 10 µM and 20 µM concentration. These results were compared with the parent compound RH which inhibited 35% and 45% lipid accumulation while the RH analog K5 inhibited the lipid accumulation by 41% and 51% at 10 and 20 µM concentration, respectively. These results well corroborated with in-silico studies.

Numerical analysis of lasing characteristics in highly bend-compensated large-mode-area ytterbium-doped double-clad leakage channel fibers.

The bend-induced mode-area reduction and thermal effects are vital factors that affect the power scaling of fiber lasers. Recently, bend-compensated large-mode-area double-clad modified hybrid leakage channel fiber (M-HLCF) has been reported with a mode area greater than 1000 µm, while sustaining the single-mode behavior at 1064 nm for high-temperature environments. In this work, the lasing characteristics of a newly designed ytterbium-doped double-clad M-HLCF (YDMHLCF) have been numerically investigated for strongly pumped conditions. The doped region size is optimally found through simulations, equivalent to the size of core diameter ∼38 µm in order to achieve maximum conversion efficiency for the bent and straight cases. Numerical simulations further confirm that a 2 m long YDMHLCF exhibits slope efficiency of 78% and conversion efficiency of 79% for the straight case and also almost the same for the practical bending radius of 7.5 cm when pumped with a 975 nm laser source.

Tunable optical parametric amplification characteristics of liquid-filled chalcogenide photonic crystal fibers.

A new technique to attain tunable parametric amplification in photonic crystal fibers (PCFs) through control of chromatic dispersion is proposed and empirically investigated. By infiltrating the air channels of the PCFs with suitable thermo-optic liquids, the zero-dispersion wavelength (ZDW) can be tailored to provide a wider gain spectrum in the mid-IR range and generate blueshifted frequency components. It is deduced that a change of 10-20 nm in the ZDW around the pump creates a gain region several hundred nanometers from the pump wavelength by only varying the temperature of the liquid externally.

Role of protocol-guided perioperative care to enhance recovery after head and neck neoplasm surgery: An institutional experience.

BACKGROUND: Enhanced recovery after surgery (ERAS) improve recovery after surgery. This study aimed to determine whether ERAS leads to a decrease in stay in the hospital and improves global and functional recovery after head and neck neoplasms surgery. METHODS: We performed a prospective case and historical control study after the ERAS application. The hospital database selected 50 confirmed eligible patients in control non-ERAS group. Prospectively 54 patients were included in the ERAS group. The primary outcome was time to readiness for discharge (TRD); secondary outcomes were the length of stay (LOS), readmission rate of up to 30 days and Quality of recovery score QoR-15. Data were compared with appropriate parametric and nonparametric tests. RESULTS: Baseline demographic data of patients were comparable between the two groups. Patients in ERAS group had significantly shorter TRD compared to the non-ERAS group 8 (6-10) vs 11 (8-16); p-value = 0.002. LOS was also significantly shorter in the ERAS group compared to the non-ERAS group [8 (7-11) vs 12 (9-17); p-value = 0.002]. Readmission at 30-days was no different, with six patients in each group. QoR-15 score was statistically better in ERAS group (94.88 ±â€¯12.50) compared to non-ERAS group (85.44 ±â€¯12.68) [p value < 0.001]. CONCLUSION: Implementing the ERAS programme decreased TRD and LOS and improved patient-reported recovery outcome QoR-15 in head and neck neoplasms surgery.

Diagnosis of gastrointestinal tuberculosis: Using cytomorphological, microbiological, immunological and molecular techniques - A study from Central India.

The present study included three groups: (A) age and gender matched control (n=24) with no previous signs of M. tuberculosis complex (MTBC) infection, (B) patients (n=28) diagnosed with gastro-intestinal TB (GITB), (C) patients (n=50) with clinical and histo-pathological signs of GITB, but were culture and AFB negative. Real time assay performed using fluorescence resonance energy transfer hybridization probes showed a positivity index of 36 % in group C, i.e. 18 were found reactive from the total 50 cases studied. In addition, immune characterization of these 18 cases showed depleted CD(4) (+) count and increased levels of IFN-γ and TNF-α cytokines. No positive case was found in group A, while in group B, out of total 28 cases studied 27 were found positive. A combinatorial diagnostic approach for rapid detection and characterization of GITB might provide specific therapeutic strategies for prevention and treatment of the infection in future.

Correlation of aberrant expression of p53, Rad50, and cyclin-E proteins with microsatellite instability in gallbladder adenocarcinomas.

Gallbladder carcinoma is an uncommon, but highly malignant tumor, with poor prognostic, and diagnostic manifestations in early stages. The Indian Council of Medical Research reported increased incidence of gallbladder carcinoma in the surviving population of the Bhopal gas tragedy that involved exposure of more than 500,000 people to methyl isocyanate gas. The severity of exposure, and increased multi-systemic morbidity in the survivors stimulated us to examine the molecular changes leading to gallbladder carcinoma. Surgically resected samples (N = 40) of gallbladder carcinoma were studied for the p53, Rad50, and cyclin-E expression by immunohistofluorescence bioimaging. Among the 40 samples, 23, 11, and 10 showed p53, Rad50, and cyclin-E expression, respectively, in moderately differentiated adenocarcinomas, demonstrating the prevalence and invasiveness of this disease in the methyl isocyanate-exposed population (P = 0.0009). Nevertheless, co-expression of Rad50, and cyclin-E with p53 was absent in adenomas with dysplasia, demonstrating their independent roles. We conclude that there was altered expression of p53, Rad50, and cyclin-E in the malignant transformation of gallbladder carcinoma in this methyl isocyanate gas-exposed cohort. Hence, these proteins may be useful as markers to identify premalignant lesions that are likely to progress into malignant adenocarcinoma.

Design and simulation of 1310 nm and 1480 nm single-mode photonic crystal fiber Raman lasers.

We have numerically investigated the Raman lasing characteristics of a highly nonlinear photonic crystal fiber (HNPCF). HNPCF Raman lasers are designed to deliver outputs at 1.3 microm and 1.48 microm wavelengths through three and six cascades of Raman Stokes cavities when the pumps of 1117 nm and 1064 nm are injected into HNPCF module, respectively. A quantum efficiency of approximately 47% was achieved in a short length of HNPCF for 1.3 microm lasing wavelength. The HNPCF design is modified further to operate in single-mode fashion keeping intact its Raman lasing characteristics. The modified HNPCF design consists of two air-hole rings where the higher-order modes in the central core are suppressed by enhancing their leakage losses drastically, thus ceasing their propagation in the short length of HNPCF. On the other hand, the fundamental mode is well confined to the central core region, unaffecting its lasing performances. Further, the lasing characteristics of HNPCF at 1480 nm are compared with conventional highly nonlinear fiber Raman laser operating at 1480 nm. It is found that one can reduce the fiber length by five times in case of HNPCF with nearly similar conversion efficiency.

Bend-insensitive lasing characteristics of single-mode, large-mode-area ytterbium-doped photonic crystal fiber.

The bend-insensitive lasing characteristics of a newly designed ytterbium-doped photonic crystal fiber (YPCF) are evaluated numerically. The designed YPCF remains single-mode and possesses large-mode-area of 1400 microm(2) at 1064 nm wavelength with the beam quality factor (M(2)) of 1.15, suggesting a diffraction-limited and continuous-wave lasing operation. The doped-region size is optimized for maximum conversion efficiency and it is found through numerical simulations that the doped radius should be more than 21 microm. The "mode expansion", which is the self-expansion of the fundamental mode within the doped region with wavelength increments on bending the fiber, is the basic physical mechanism to give the bend-insensitive lasing performances of YPCF. It leads to an unusual variation of overlap factor when the wavelength is increased. A 41 cm long piece of YPCF demonstrates more than 83% of slope efficiency with 75% of conversion efficiency when pumped with a 975 nm laser source delivering an input power of 1 W.

Strategies for realizing photonic crystal fiber bandpass filters.

Numerical design strategies are presented to achieve efficient broad or narrow band-pass filters based on index-guiding, solid-core, and single-mode photonic crystal fibers (PCFs). The filtering characteristics have been verified through BPM solver. By scaling the pitch constant, the bandpass window can be shifted accordingly. The fiber design constitutes a fluorine-doped central core, enlarged air-holes surrounding the down-doped core, and small air-holes in the cladding. The proposed bandpass filter is based on controlling the leakage losses, so one can tune filter characteristics simply by changing its length. From numerical simulations we show that for large values of air-hole diameter in the first ring, the bandpass window is narrow, while for low doping concentration and small sized air-holes in the first ring, bandpass window is very broad. We also simulate how the hole-size and number of rings in the PCF cladding affects the device characteristics. We find that a 5-cm long PCF with down-doped core and eleven rings of air-holes can result in approximately 440 nm 3-dB bandwidth with more than 90% of transmission. The longer device has reduced transmission and smaller 3-dB bandwidth. Tolerance analysis has also been performed to check the impact of fiber tolerances on the performance of the PCF bandpass filter. It has been observed that the decrement in cladding hole-diameter by 1% reduces the transmission to 21% from its peak value of 93%, however +/-1% tolerance in the inner hole-diameter degrades the transmission to 75% from its peak.

Measurement of chromatic dispersion and Raman gain efficiency of a hole-assisted fiber: Influence of bend.

We have experimentally measured the Raman gain efficiency (RGE) and chromatic dispersion (CD) of a hole-assisted fiber (HAF). The RGE of a HAF was characterized using standard pump on/off technique while the CD of the fiber was measured using optical network analyzer. Theoretical simulations of the modal characteristics and the RGE of HAF were carried out using an accurate full-vectorial finite element method. Further, the bending effects on the CD and the RGE of a HAF with a smallest feasible bending radius are demonstrated. It was found that the CD increases while the RGE is decreased by bending HAF in a smallest bending radius of 5 mm. Numerical predictions from the theory are shown to be in good agreement with the experimental results.

Rosai Dorfman syndrome with extranodal manifestation.

Rosai Dorfman Syndrome (RDS) is a benign condition and a rare cause of cervical lymphadenopathy. It usually occurs in the first decade of life and manifest as massive enlargement of cervical lymph nodes. The disease has a benign course and involvement of the nasal cavity as an extranodal site is exceptional. A 22-year-old male presented as progressive massive bilateral cervical lymphadenopathy accompanied with nasal obstruction and occasional episodes of epistaxis. A FNAC from cervical lymph node and biopsy from nasal mass was compatible with RDS.

Benign esophageal stricture following aluminium phosphide poisoning.

Aluminium phosphide is often implicated in accidental and suicidal poisoning in India. Ingestion of even half a fresh tablet invariably results in death, whereas exposed tablets are usually considered harmless. We report two cases of short-segment esophageal strictures that occurred following ingestion of exposed tablet of aluminium phosphide. Both cases could be successfully managed by endoscopic dilatation.

Incidental carcinoma of the gallbladder.

Incidental gallbladder carcinoma (GBC) is a difficult management issue as there are no established guidelines. Laparoscopic cholecystectomy is associated with increased dissemination of the tumour cells (both in the peritoneal cavity and port sites). Depth of tumour invasion (T stage) and positive surgical margins are the most important prognostic factors, although tumour differentiation, lymphatic, perineural and vascular invasion may also affect the outcome. Simple cholecystectomy is adequate for mucosal (T1a) lesions only. For T1b tumours port site/wound excision with second radical operation (probably extended cholecystectomy -- wedge liver excision with regional lymphadenectomy) should be advised. T2 tumours should be treated with second radical operation (extended cholecystectomy or excision of medial liver segments 4b and 5 or 4, 5 and 8 with regional lymphadenectomy with or without excision of the extra-hepatic bile duct). Few T3 tumours can be cured and in some survival time may be prolonged by a second radical operation. More extensive liver resection (segments 4b and 5 or segments 4, 5 and 8) with regional lymphadenectomy with excision of the extra-hepatic bile duct should be advised. A second radical operation may palliate some T4 tumours. In the absence of extensive nodal disease, this operation may prolong the survival time. Excision of the extra-hepatic bile duct should be undertaken whenever the tumour involves the cystic duct margin or the extra-hepatic biliary tree. Epidemiology, risk factors, aetiopathogenesis and the modes of spread of GBC are discussed in relation to appropriateness of the second radical operation. Indications, types and role of the second radical operation are discussed.

A comparison of 5-day and 8-day drainage following mastectomy and axillary clearance.

AIMS: Mastectomy and axillary clearance are standard operations for the treatment of breast carcinoma. Drainage of the mastectomy site and axilla is often required to allow accumulating blood and inflammatory fluids to escape. However, there is a lack of data relating to how long suction drains should stay in situ after major breast surgery. In our study we have tried to address this deficit by comparing the efficacy of 5-day post-operative drainage with 8-day post-operative drainage. METHODS: Patients requiring mastectomy and axillary clearance were randomized to having drains removed on day 5 or day 8 post-operatively. The number of lymphoceles, aspirations and total aspiration volumes in chest and axillary drains were compared. RESULTS: From a total of 121 patients enrolled into the study, 64 patients were randomized to the 5-day group and 57 to the 8-day group. There were significant differences regarding the number of aspirations and total aspiration volumes in chest and axillary drains between the two groups, favouring 8-day drainage. However the number of lymphoceles drained in the 5-day group was significantly higher than the 8-day group. CONCLUSIONS: Five-day post-operative drainage is as safe as 8-day post-operative drainage in the management of patients undergoing major breast surgery, but results in an increase in lymphocele aspiration and aspiration volume.

Traumatic 'degloving' of the colon in blunt abdominal injury.

We describe two cases of traumatic 'degloving' of the colon in blunt abdominal trauma. This is an extremely rare injury with the potential to present late. The mechanism of injury appears to be a combination of focal blunt abdominal trauma associated with a shearing force. The potential diagnostic dilemma posed by colonic 'degloving' is outlined and following review of the literature we conclude that CT scanning is the most reliable way of detecting such injuries, if emergency laparotomy is not indicated.

Two-layer repair of the transversalis fascia is sufficient for inguinal hernia repair.

The Shouldice four-layer repair is considered to be the gold standard procedure for repair of inguinal hernia with low recurrence rates around 1%. Tension-free two-layer repair of the transversalis fascia may be all that is required to avoid recurrence. We compared the early recurrence rate after two-layer repair of the transversalis fascia or the standard four-layer Shouldice technique in a randomised study of elective inguinal herniorrhaphy. In 48 patients (53 repairs) who had a two-layer transversalis fascia repair, there was one recurrence (2%) in the first 12 months after operation, though there was one more recurrence within 36 months (total 4%). In 39 patients who had a four-layer Shouldice repair (42 repairs), there was no recurrence at 12 months but at 36 months two recurrences (5%) were found. We conclude that a two-layer repair of the transversalis fascia is anatomically correct, physiologically sound and can provide equivalent results to the standard Shouldice repair for inguinal hernia.

Six-fold suture:wound length ratio for abdominal closure.

Midline laparotomy incision is generally closed as a continuous single layer with monofilament suture. To achieve safe abdominal closure, it is advised to have a suture:wound length (SL:WL) ratio of more than 4:1. The importance of a high SL:WL ratio led us to standardise a safe abdominal closure technique. We calculated the subsequent SL:WL ratio and support our finding with a mathematical model. Between March 1996 and February 1997, 100 consecutive patients undergoing elective or emergency laparotomy through a midline incision were entered into this prospective study. The wounds were closed with a single layer continuous suture to approximate the abdominal muscles. Suture and wound lengths were recorded. Patients were followed for one year. Five patients developed incisional hernia at 12 months postoperatively. There was no burst abdomen. The mean SL:WL ratio: was 6.2:1. A mathematical model confirms that a SL:WL ratio of 6:1 should be achieved with this suture technique. We recommend an optimal SL:WL ratio: greater than or equivalent to 6:1 to achieve safe closure of midline laparotomy incision.

Neuroendocrine tumors of the pancreas.

Neuroendocrine tumors of the pancreas (NETP) are rare. We report our surgical experience of 11 patients with NETP. These included 5 patients with benign insulinomas. Raised serum insulin and C-peptide levels with hypoglycemia were always diagnostic. Ultrasonography, CT, visceral angiography, arterial stimulation and venous sampling, and intraoperative ultrasound localized the tumor in 0/5, 1/5, 3/4, 2/2, 3/3 cases, respectively. The 6 other malignant NETP (one gastrinoma, 2 carcinoids, 3 non-functioning) were managed by pancreatic resection (Whipple's operation = 3, distal pancreatectomy with total gastrectomy = 1, total pancreatectomy = 1, distal pancreatectomy with left nephrectomy and proximal gastrectomy = 1). Two patients died postoperatively. We had 5 major and 2 minor postoperative complications, with 2 deaths. During follow up from 1 to 7 years, one patient with malignant carcinoid tumor died at two and half years, of local recurrence. The other 8 patients are disease-free with good quality of life.

Richter's hernia: a rare presentation of abdominal tuberculosis.

Intestinal obstruction due to Richter's hernia has not been reported in abdominal tuberculosis. This 21-year-old man with abdominal tuberculosis presented with small gut obstruction due to Richter's hernia associated with ascites and patent right processus vaginalis (PV). He underwent laparotomy with reduction of Richter's hernia and closure of the PV at the right deep inguinal ring.

Small bowel leiomyoma: an unusual presentation.

Dual pathology having similar symptomatology is uncommon. We present a patient whose symptoms, although not absolutely typical of inguinal hernia, were attributed to bilateral irreducible inguinal hernias and were treated surgically. He remained symptomatic and later, was found to have an intraluminal leiomyoma of the jejunum, which was then removed. We suggest that the presence of any unusual clinical features should prompt further investigation to detect an alternative causative pathology.