Enhancement of mechanical and corrosion resistance properties of electrodeposited Ni-P-TiC composite coatings.

In the present study, the effect of concentration of titanium carbide (TiC) particles on the structural, mechanical, and electrochemical properties of Ni-P composite coatings was investigated. Various amounts of TiC particles (0, 0.5, 1.0, 1.5, and 2.0 g L-1) were co-electrodeposited in the Ni-P matrix under optimized conditions and then characterized by employing various techniques. The structural analysis of prepared coatings indicates uniform, compact, and nodular structured coatings without any noticeable defects. Vickers microhardness and nanoindentation results demonstrate the increase in the hardness with an increasing amount of TiC particles attaining its terminal value (593HV100) at the concentration of 1.5 g L-1. Further increase in the concentration of TiC particles results in a decrease in hardness, which can be ascribed to their accumulation in the Ni-P matrix. The electrochemical results indicate the improvement in corrosion protection efficiency of coatings with an increasing amount of TiC particles reaching to ~ 92% at 2.0 g L-1, which can be ascribed to a reduction in the active area of the Ni-P matrix by the presence of inactive ceramic particles. The favorable structural, mechanical, and corrosion protection characteristics of Ni-P-TiC composite coatings suggest their potential applications in many industrial applications.

Fixed-time terminal synergetic observer for synchronization of fractional-order chaotic systems.

In this paper, a fixed-time terminal synergetic observer for synchronization of fractional-order nonlinear chaotic systems is proposed. First, fixed-time terminal attractors for fractional-order nonlinear systems are introduced on the basis of fixed-time stability of integer-order nonlinear differential equations and on defining particular fractional-order macro-variables. Second, a new synergetic observer dedicated to the synchronization of fractional-order chaotic systems is developed. The proposed observer converges in a predefined fixed-time uniformly bounded with respect to initial conditions. Thanks to the step-by-step procedure, only one communication channel is used to achieve the synchronization. Third, a fixed-time synergetic extended observer with unknown input is constructed to simultaneously estimate the state variables and to recover the unknown input. Finally, computer simulations are performed to illustrate the efficiency of the proposed synchronization method and its application in a secure communication scheme.

Pharmacokinetics and in vivo distribution of optimized PLGA nanoparticles for pulmonary delivery of levofloxacin.

OBJECTIVES: The aim of this study was to develop and optimize levofloxacin loaded PLGA nanoparticles (LN) for pulmonary delivery employing screening and experimental design and evaluate their in-vitro and in-vivo performance. The objective was to achieve Mass Median Aerodynamic Diameter (MMAD) of LN of less than 5µm, sustain the drug release up to 120 h and a higher AUC/MIC at the site of action. METHODS: LN were prepared by modified emulsion solvent evaporation technique employing high speed homogenization, probe sonication and subsequent lyophilization. KEY FINDINGS: The Pareto chart from Placket Burman screening design revealed that homogenization speed and amount of PLGA were found to be significant (P < 0.05). Further analysis by 3 full-factorial design revealed that F-ratio was found to be far greater than the theoretical value (P < 0.05) for each regression model. CONCLUSION: The optimized formulation with desirability value 0.9612 showed mean particle size of 146 nm, MMAD of 4.40 µm and sustained the drug release up to 120 h in simulated lung fluid. Augmentation in Cmax (1.71-fold), AUC 0-∞ (5.46-fold), Mean Residence Time (6.64-fold) and AUC/MIC (6.21-fold) of LN through pulmonary route was found to significantly higher (P < 0.05) than levofloxacin (p. o.).

Randomised comparison of two household survey modules for measuring stillbirths and neonatal deaths in five countries: the Every Newborn-INDEPTH study.

BACKGROUND: An estimated 5·1 million stillbirths and neonatal deaths occur annually. Household surveys, most notably the Demographic and Health Survey (DHS), run in more than 90 countries and are the main data source from the highest burden regions, but data-quality concerns remain. We aimed to compare two questionnaires: a full birth history module with additional questions on pregnancy losses (FBH+; the current DHS standard) and a full pregnancy history module (FPH), which collects information on all livebirths, stillbirths, miscarriages, and neonatal deaths. METHODS: Women residing in five Health and Demographic Surveillance System sites within the INDEPTH Network (Bandim in Guinea-Bissau, Dabat in Ethiopia, IgangaMayuge in Uganda, Matlab in Bangladesh, and Kintampo in Ghana) were randomly assigned (individually) to be interviewed using either FBH+ or FPH between July 28, 2017, and Aug 13, 2018. The primary outcomes were stillbirths and neonatal deaths in the 5 years before the survey interview (measured by stillbirth rate [SBR] and neonatal mortality rate [NMR]) and mean time taken to complete the maternity history section of the questionnaire. We also assessed between-site heterogeneity. This study is registered with the Research Registry, 4720. FINDINGS: 69 176 women were allocated to be interviewed by either FBH+ (n=34 805) or FPH (n=34 371). The mean time taken to complete FPH (10·5 min) was longer than for FBH+ (9·1 min; p<0·0001). Using FPH, the estimated SBR was 17·4 per 1000 total births, 21% (95% CI -10 to 62) higher than with FBH+ (15·2 per 1000 total births; p=0·20) in the 5 years preceding the survey interview. There was strong evidence of between-site heterogeneity (I2=80·9%; p<0·0001), with SBR higher for FPH than for FBH+ in four of five sites. The estimated NMR did not differ between modules (FPH 25·1 per 1000 livebirths vs FBH+ 25·4 per 1000 livebirths), with no evidence of between-site heterogeneity (I2=0·7%; p=0·40). INTERPRETATION: FPH takes an average of 1·4 min longer to complete than does FBH+, but has the potential to increase reporting of stillbirths in high burden contexts. The between-site heterogeneity we found might reflect variations in interviewer training and survey implementation, emphasising the importance of interviewer skills, training, and consistent implementation in data quality. FUNDING: Children's Investment Fund Foundation.

Synthesis and Performance Evaluation of Pulse Electrodeposited Ni-AlN Nanocomposite Coatings.

This research work presents the microscopic analysis of pulse electrodeposited Ni-AlN nanocomposite coatings using SEM and AFM techniques and their performance evaluation (mechanical and electrochemical) by employing nanoindentation and electrochemical methods. The Ni-AlN nanocomposite coatings were developed by pulse electrodeposition. The nickel matrix was reinforced with various amounts of AlN nanoparticles (3, 6, and 9 g/L) to develop Ni-AlN nanocomposite coatings. The effect of reinforcement concentration on structure, surface morphology, and mechanical and anticorrosion properties was studied. SEM and AFM analyses indicate that Ni-AlN nanocomposite coatings have dense, homogenous, and well-defined pyramid structure containing uniformly distributed AlN particles. A decent improvement in the corrosion protection performance is also observed by the addition of AlN particles to the nickel matrix. Corrosion current was reduced from 2.15 to 1.29 µA cm-2 by increasing the AlN particles concentration from 3 to 9 g/L. It has been observed that the properties of Ni-AlN nanocomposite coating are sensitive to the concentration of AlN nanoparticles used as reinforcement.

Development and Characterization of Multifunctional Directly Compressible Co-processed Excipient by Spray Drying Method.

The present investigation was carried out to develop and characterize a multifunctional co-processed excipient for improving the compressibility of poorly compressible drugs. Etodolac was used as a model drug. Microcrystalline cellulose (MCC), lactose monohydrate (lactose), and StarCap 1500 (StarCap) were selected as components of the co-processed excipient. The spray drying method was used for co-processing of excipients. D-optimal mixture design was applied to optimize the proportion of component excipients. Statistical analysis of the D-optimal mixture design revealed that all response variables were significantly affected by the independent variables (p value < 0.05). Optimized composition was obtained from the desirability function. The optimized composition of the co-processed excipient was found to be 30% MCC, 25% lactose, and 45% StarCap. This optimized batch was evaluated for flow properties, compressibility parameters such as Kawakita's and Kuno's equation and Heckel's equation, and dilution potential. Evaluation parameters for flow properties (angle of repose, Carr's index, and Hausner's ratio) suggested excellent flow character. The parameters of Kawakita's and Kuno's equation and Heckel's equation suggested improvement in the compressibility of the model drug. Dilution potential was found to be 40%, and based on that, tablets of the model drug were formulated and evaluated for general evaluation parameters of tablets. All the parameters were found to be within the acceptance criteria which concluded that the multifunctional directly compressible co-processed excipient was prepared successfully that improved the compressibility of the poorly compressible model drug etodolac along with spray drying as an efficient method for the preparation of co-processed excipient.

Microemulgel of Voriconazole: an Unfathomable Protection to Counter Fungal Contagiousness.

BACKGROUND: Fluconazole and ketoconazole both have poor minimum inhibitory concentration than voriconazole. Voriconazole had serious side effects in oral and intravenous doses. It has poor water solubility. The objective of the study was to prepare and optimize microemulgel of voriconazole for topical delivery. AIM: Formulation, development, and evaluation of voriconazole microemulgel for topical delivery. METHODS: Oil and emulsifi ers selected were on the basis of equilibrium solubility study and emulsification property respectively. The pseudo-ternary plot and constrained simplex lattice design were applied for preparation of microemulsions. Microemulsions were subjected to micelle size, zeta potential, polydispersity index, and in vitro study. They were optimized by Design-Expert® 9.0.3.1 software. Formulation, development, evaluation and optimization of microemulgel were carried out. Microbial assay of an optimized batch of microemulgel was performed. RESULTS: Solubility of voriconazole in Parker Neem® oil was 7.51±0.14 mg/g. Acrysol™K-150: PEG-400 in 4:1 ratio had the highest area for microemulsion. 59.2% Acrysol™K-150, 14.8% PEG-400, 11% Parker Neem® oil, 15% rose water, and 1% voriconazole as an optimized batch of microemulsion was selected for preparation of microemulgel. Carbomer 934P found a good gelling agent in 0-2% w/w concentration. An optimized batch of microemulgel had 0.974 desirability value. An optimized batch of microemulgel and Nizral® cream had 37.32±0.63% and 26.45±0.63% zones of inhibition. CONCLUSION: Topical antifungal treatment was successfully achieved with voriconazole microemulgel.

Enhanced synthesis of andrographolide by Aspergillus niger and Penicillium expansum elicitors in cell suspension culture of Andrographis paniculata (Burm. f.) Nees.

BACKGROUND: Andrographis paniculata (Burm. f.) Nees is an important medicinal plant which has enormous applications in pharmaceutical industries. Cell suspension culture of Andrographis paniculata (Burm. f.) Nees. was treated with Aspergillus niger and Penicillium expansum elicitors to enhance the synthesis of andrographolide, the bioactive constituent of A. paniculata. RESULT: The elicitation treatment with fungal elicitors (A. niger and P. expansum) was observed to be most suitable for eliciting andrographolide production in the culture. The quantification of andrographolide was done using High Performance Liquid Chromatography (HPLC) technique. A. niger extract (1.5 ml with10 days treatment duration) revealed 6.94 fold increase in andrographolide content (132 µg) which was higher than the control (19 µg). P. expansum elicitor (0.6% with 8 days treatment duration) could reveal 6.23 fold enhancement in andrographolide content (81.0 µg) over control (13 µg). CONCLUSION: The results obtained reveal that the longer treatment duration is most favorable for the elicitation of andrographolide using both the fungal elicitors.

Molecular genetics of beta-thalassaemia syndrome in Pakistan.

This molecular genetics study was conducted in Karachi, Pakistan from 2004 to 2006 to provide guidelines for prenatal diagnosis programmes in the country. Blood samples of patients with beta-thalassaemia minor (n=200) and beta-thalassaemia major (n=150) were collected from hospitals, transfusion centres and diagnostic laboratories from different districts of Karachi, representing 5 major ethnic groups. Molecular analysis revealed 11 genetic mutations of the beta-thalassaemia gene, among which 5 mutations accounted for 88% of the total beta-thalassaemia genes identified [IVS-1-5 (G-C), Fr 8/9 (+G), Fr 41/42 (-TTCT), IVS-1-1 (G-T) and Del 619]. Other mutations identified were: CAP+1 IVS-II-1 (G-A), Cd 5 (-CT), Cd 15 (G-A). Cd 16 and Cd 30.

Molecular genetics of beta-thalassaemia syndrome in Pakistan

This molecular genetics study was conducted in Karachi, Pakistan from 2004 to 2006 to provide guidelines for prenatal diagnosis programmes in the country. Blood samples of patients with beta-thalassaemia minor [n = 200] and beta-thalassaemia major [n = 150] were collected from hospitals, transfusion centres and diagnostic laboratories from different districts of Karachi, representing 5 major ethnic groups. Molecular analysis revealed 11 genetic mutations of the beta-thalassaemia gene, among which 5 mutations accounted for 88% of the total beta-thalassaemia genes identified [IVS-1-5 [G-C], Fr 8/9 [+G], Fr 41/42 [-TTCT], IVS-1-1 [G-T] and Del 619]. Other mutations identified were: CAP+1, IVS-II-1 [G-A], Cd 5 [-CT], Cd 15 [G-A], Cd 16 and Cd 30

Cigarette smoking, birthweight and osteoporosis in adulthood: results from the hertfordshire cohort study.

We looked for interaction between early environment and adult lifestyle in determination of bone mineral content (BMC) and bone mineral density (BMD) among 498 men and 468 women for whom birth records were available. Participants completed a health questionnaire, and bone densitometry (DXA) of the lumbar spine and femoral neck performed.We found no relationships between cigarette and alcohol consumption, physical activity and either BMC or BMD after adjustment for age, body mass index, dietary calcium, social class, HRT use and years since menopause. However, male current smokers in the lowest third of birth weight had lower femoral neck BMD than ex- or never smokers from the lowest birth weight third (p value for interaction term = 0.04). Similar trends were seen with femoral neck BMC and lumber spine BMC.Individuals of lower birth weight may be particularly vulnerable to the effects of bone noxious stimuli such as cigarette smoking.

Consenting practice for open inguinal hernia repairs - are we failing to warn patients of serious complications?

INTRODUCTION: Open inguinal hernia repairs are one of the most commonly performed procedures in the UK. The procedure can sometimes result in considerable morbidity. It is imperative that the consenting process for this procedure is meticulous. This allows the patient to make a fully informed decision as they are aware of potential complications. In turn, this reduces the risk of future litigation. The aim of this study was to examine the adequacy of consenting for open inguinal hernia repairs, in particular, focusing on serious risks associated with the procedure. PATIENTS AND METHODS: The notes of male patients who had undergone open inguinal hernia repair over a 6-month period were identified by the IT department. Inclusion and exclusion criteria were defined, giving a total of 97 male patients. Their consent forms were examined, focusing on: (i) the complications mentioned; and (ii) the grade of the consentor. A proforma was filled in for each of these patients and the data collated. RESULTS: Of the 97 patients in the study, 25.7% of patients were consented by a consultant, 54.6% by a specialist registrar, and 19.6% by a senior house officer/FY2. The most commonly recorded risks included infection (100%) and bleeding (100%). Serious complications such as chronic pain (consented for at an average of 14%), testicular complications (45.3%) and visceral injury (52.1%) were poorly accounted for at all levels. CONCLUSIONS: Consultants and juniors alike are not adequately consenting patients for inguinal hernia repairs, omitting serious complications such as chronic pain, recurrence and testicular complications. This leaves surgical teams vulnerable to claims for negligence. Good consenting practice may ultimately benefit both patient and surgeon.

Altered endothelin receptor subtypes in colorectal cancer.

BACKGROUND: The vasoactive peptide endothelin-1 (ET-1) acts via two endothelin receptor subtypes, ETA (ETAR) and ETB (ETBR). ET-1 and ETAR are overexpressed in colorectal cancer tissues. In vitro, ET-1 acting via ETAR, is a mitogen for colorectal cancer cells. To identify other potential stimulatory loops, we investigated the distribution and cell-specific localization of both ETAR and ETBR in tissue sections from patients with colorectal cancer. METHODS: Frozen sections from specimens of colorectal cancer (n=9) and normal colon (n=9) were cut and subjected to either (i) autoradiography or (ii) a combination of cell type-specific immunohistochemistry, using antibodies against fibroblasts (AS02), endothelial cells (CD31) or nerve fibres (NF200) and in-vitro receptor microautoradiography, using ETAR-specific and ETBR-specific radioligands. RESULTS: ETARs were upregulated in all cell types, apart from nerve, in cancer compared with normal colon (1:1.59 normal to cancer). Specifically, ETAR binding was highest in cancer-associated blood vessels and fibroblasts and to a lesser extent in epithelial cancer cells. In contrast, ETBRs were the predominant receptors in normal colon (1:0.59 normal to cancer) and were markedly down-regulated in cancer-associated blood vessels, fibroblasts and to a lesser extent in epithelial cells. Nerve colocalization was demonstrated, but remained unchanged for all tissues. CONCLUSION: The shift in ET receptor binding observed in epithelial cancer cells and cancer-associated fibroblasts and endothelial cells may favour ET-1 signals contributing to colorectal cancer growth and neovascularization via ETAR. This may provide the basis for therapeutic use of specific ETAR antagonists as adjuvant treatment of colorectal cancer.

Inflammatory pseudotumour of the liver: the residuum of a biliary cystadenoma?

Inflammatory pseudotumour is a rare form of a liver mass. We report the case of a 28-year-old man presenting with obstructive jaundice, in whom an inflammatory pseudotumour arose with the resolution of a mucus secreting cystic liver lesion. The initial features suggested an intrahepatic cystadenoma or cystadenocarcinoma, which on its involution left a solid mass. Histopathology showed an inflammatory pseudotumour with no evidence of malignancy. A similar case has been reported recently, with the development of an inflammatory pseudotumour following collapse of a liver cyst seen on imaging. These two cases may shed some light on the origins of these rare liver lesions.

Thrombotic obstruction of bileaflet mechanical prosthetic heart valves: early diagnosis and management.

BACKGROUND: Thrombosis of mechanical prosthetic heart valves (TMPHV) is one of the major complications that accounts for the highest morbidity and mortality related to Bileaflet Mechanical Prosthetic Heart Valves (BMPHV). MATERIALS AND METHODS: During the last six years we had ten cases of bileaflet mechanical valve thrombosis. All patients had undergone emergency surgical interventions except one who developed systemic embolization and massive brain insult immediately after admission for surgery and died two months later. We divided the patients in two groups, first group includes five patients who came in acute pulmonary edema and emergency operation was done either to replace the thrombosed BMPHV (in two) or successful thrombectomy was achieved (in three) and all of them have survived. The second group (four patients) presented with cardiogenic shock and required emergency femoro-femoral bypass. Two patients survived after thrombectomy and the other two could not come off bypass after changing the TMPHV and in spite of Intra-aortic balloon pump, they died 24 and 48 hours after the procedure. All patients received intravenous heparin on admission. Preoperative i.v. Streptokinase was given in two cases, of which one required thrombectomy and the other had valve replacement and died 24 hours later. RESULTS: Early diagnosis and operation still had the best results in TMPHV though thrombolytic therapy was successful in few reported early presented cases. All patients who had thrombectomy of the TMPHV have survived without any morbidity. Follow up of survived patients ranged between two months and six years with a mean of 24.1 months. It is worth attempting thrombectomy of the thrombosed BMPHV rather than re-replacement which carries higher morbidity and mortality, because of the longer ischemic arrest during operation which further depletes the energy of the myocardium. CONCLUSIONS: Though this is a small number of patients to make a definite conclusion, thrombectomy was more feasible in CarboMedics Prosthetic Heart Valves, since its in situ rotation that allows reorientation of its leaflets and declotting of valve hinge to be performed.

Early experience with transmyocardial laser revascularization.

Conventional treatment of coronary artery disease consists of either Coronary Artery Bypass Grafting (CABG), medical therapy or percutaneous transluminal coronary angioplasty (PTCA) or a combination. However, certain group of patients do not even qualify for CABG. Transmyocardial Laser Revascularization (TMR) is a unique new surgical modality specially for that sub group of patient population who have small and diffuse coronary artery disease not suitable for grafting. King Fahad Heart Center initiated its TMR program in February, 1994 and until February, 1996, 100 patients under went the TMR procedure. Eighty-one were males and 19 females with a mean average age of 55 years. Seventy-nine patients had 3 vessel disease (VD) and 66 patients had non-graftable small vessels. Ten patients had left ventricular ejection fraction (LVEF) less than 30%. All the patients underwent a strict protocol of follow-up. The pre and post TMR assessment at six months and 12 months follow-up showed an increase in LVEF at six and 12 months as compared to pre TMR level. The exercise time also increased from a base line level at six months and showed further improvement at 12 months which was statistically significant (p < 0.05) along-with VO2 max, which also showed improvement. Clinically, haemodynamically and symptomatically these patients showed significant improvement and use of anti-anginal drugs (87%) was reduced to minimum. Isotope myocardial perfusion scan on 15 segment viability score showed an improvement from pre TMR level of 33.8 to 45.9 at post TMR 12 months follow up. The surgical mortality in this high risk TMR population was 10%. TMR was found to be a reasonable alternative to medical treatment in patients with angina due to diffuse and or small vessel disease or occluded previous grafts not amenable to CABG.

Papillary thyroid carcinoma: demographics, treatment, and outcome in eleven pediatric patients treated at a single institution.

We describe 11 cases (8 females, 3 males) of papillary thyroid carcinoma in children treated at St. Jude Children's Research Hospital over a 33-year period, and review the literature. Ages ranged from 7-25 years (median, 16 years). Six patients had primary papillary thyroid carcinoma. Five patients had secondary papillary thyroid carcinoma after treatment of Hodgkin's disease (n = 2), acute lymphoblastic leukemia (n = 2), and neuroblastoma (n = 1) with chemotherapy and cervical radiation. The typical presentation was either cervical lymphadenopathy or a thyroid mass of short duration. Treatment consisted of thyroidectomy, cervical lymph node dissection, and postoperative thyroid hormone replacement (n = 1), parathyroid reimplantation (n = 1), 131I ablation (n = 4), external-beam irradiation (n = 1), and chemotherapy with doxorubicin (n = 1) or carboplatin and topotecan (n = 1). Nine patients are alive without evidence of disease 3.0-22.4 years from diagnosis. One patient has persistent but stable disease 17.3 years after diagnosis. One patient relapsed with metastatic lung disease 0.3 years after the initial diagnosis. He continues to do well after a brief but unsustained complete radiographic remission of disease to combination chemotherapy with carboplatin and topotecan. Our review supports excellent long-term outcome for primary or secondary papillary thyroid carcinoma in pediatric patients although complications may require close follow-up in a multidisciplinary setting.

Ectopic parathyroid adenomas: multi-imaging modalities and its management.

Advancements in imaging technology have led to better diagnoses of ectopic parathyroid adenomas. Although surgery is curative in the majority of patients with parathyroid adenomas in normal preoperative locations, imaging is definitely required in ectopic adenomas in the neck and more importantly in the chest. The various imaging modalities used in the diagnosis of parathyroid adenomas are isotopic techniques, MRI, CT, ultrasound, arteriography, and venous sampling for parathormone. This review presents four patients studied with different diagnostic techniques resulting in cures with surgery or arteriographic ablation. The literature survey suggests the sensitivity of Tc-99m MIBI scanning to be more than 90%, MRI 70-75%, and CT scanning slightly lower. On the basis of the authors' experience and a literature review, a combination of MIBI scanning and MRI appears to be the most logical approach. If these two tests do not provide sufficient diagnostic confidence, then CT or a contrast arteriogram should be considered. Recent advances in arteriography/catheters have made angiographic ablation with alcohol or contrast material possible in patients who cannot undergo surgery.

Treatment of calcinosis with diltiazem.

OBJECTIVE: To test the hypothesis that the calcium antagonist diltiazem is effective in the treatment of calcinosis. METHODS: Diltiazem, 240-480 mg/day, was given to 4 patients with idiopathic or CREST-related (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) calcinosis for 1-12 years. Serial radiographs of the affected areas, using identical technique, and clinical evaluations were obtained. A fifth patient, who did not tolerate diltiazem, received verapamil, 120 mg/day for 18 months. RESULTS: All patients taking diltiazem had a reduction or disappearance of the calcific lesions, with striking clinical improvement. One patient's case was followed for 12 years. The response to diltiazem during the first 5 years of treatment has been previously reported in detail; however, over 7 years of additional treatment, there was further reduction of the lesions. One patient developed a large calcific lesion while receiving verapamil for hypertension, and after verapamil was replaced with diltiazem, there was a dramatic response. Verapamil was ineffective in the fifth patient, who did not tolerate diltiazem. CONCLUSION: Long-term treatment with diltiazem, but not verapamil, is effective in calcinosis.