Use of Advanced Flexible Modeling Approaches for Survival Extrapolation from Early Follow-up Data in two Nivolumab Trials in Advanced NSCLC with Extended Follow-up.

OBJECTIVES: Immuno-oncology (IO) therapies are often associated with delayed responses that are deep and durable, manifesting as long-term survival benefits in patients with metastatic cancer. Complex hazard functions arising from IO treatments may limit the accuracy of extrapolations from standard parametric models (SPMs). We evaluated the ability of flexible parametric models (FPMs) to improve survival extrapolations using data from 2 trials involving patients with non-small-cell lung cancer (NSCLC). METHODS: Our analyses used consecutive database locks (DBLs) at 2-, 3-, and 5-y minimum follow-up from trials evaluating nivolumab versus docetaxel in patients with pretreated metastatic squamous (CheckMate-017) and nonsquamous (CheckMate-057) NSCLC. For each DBL, SPMs, as well as 3 FPMs-landmark response models (LRMs), mixture cure models (MCMs), and Bayesian multiparameter evidence synthesis (B-MPES)-were estimated on nivolumab overall survival (OS). The performance of each parametric model was assessed by comparing milestone restricted mean survival times (RMSTs) and survival probabilities with results obtained from externally validated SPMs. RESULTS: For the 2- and 3-y DBLs of both trials, all models tended to underestimate 5-y OS. Predictions from nonvalidated SPMs fitted to the 2-y DBLs were highly unreliable, whereas extrapolations from FPMs were much more consistent between models fitted to successive DBLs. For CheckMate-017, in which an apparent survival plateau emerges in the 3-y DBL, MCMs fitted to this DBL estimated 5-y OS most accurately (11.6% v. 12.3% observed), and long-term predictions were similar to those from the 5-y validated SPM (20-y RMST: 30.2 v. 30.5 mo). For CheckMate-057, where there is no clear evidence of a survival plateau in the early DBLs, only B-MPES was able to accurately predict 5-y OS (14.1% v. 14.0% observed [3-y DBL]). CONCLUSIONS: We demonstrate that the use of FPMs for modeling OS in NSCLC patients from early follow-up data can yield accurate estimates for RMST observed with longer follow-up and provide similar long-term extrapolations to externally validated SPMs based on later data cuts. B-MPES generated reasonable predictions even when fitted to the 2-y DBLs of the studies, whereas MCMs were more reliant on longer-term data to estimate a plateau and therefore performed better from 3 y. Generally, LRM extrapolations were less reliable than those from alternative FPMs and validated SPMs but remained superior to nonvalidated SPMs. Our work demonstrates the potential benefits of using advanced parametric models that incorporate external data sources, such as B-MPES and MCMs, to allow for accurate evaluation of treatment clinical and cost-effectiveness from trial data with limited follow-up. HIGHLIGHTS: Flexible advanced parametric modeling methods can provide improved survival extrapolations for immuno-oncology cost-effectiveness in health technology assessments from early clinical trial data that better anticipate extended follow-up.Advantages include leveraging additional observable trial data, the systematic integration of external data, and more detailed modeling of underlying processes.Bayesian multiparameter evidence synthesis performed particularly well, with well-matched external data.Mixture cure models also performed well but may require relatively longer follow-up to identify an emergent plateau, depending on the specific setting.Landmark response models offered marginal benefits in this scenario and may require greater numbers in each response group and/or increased follow-up to support improved extrapolation within each subgroup.

Papillary Carcinoma of Breast: Clinicopathological Characteristics, Management, and Survival.

Objective: To study clinicopathological features, treatment strategies, and prognosis of papillary carcinoma of breast. Material and Methods. Data from 58 patients were retrospectively reviewed from January 2010 to December 2016. Four types of papillary carcinoma (on final resected specimen) were included, i.e., invasive papillary carcinoma (IPC), intracystic (encapsulated) papillary carcinoma (EPC), solid papillary carcinoma (SPC), and papillary DCIS (ductal carcinoma in situ). Various features of the four types were observed and compared. Results: Of the 58 patients, 8 were males (13.7%). The mean age at presentation was 61 years; the mean tumor size was 33 mm. The frequency of each histological type was as follows: IPC (n = 22/38%), EPC (n = 22/38%), SPC (n = 12/20.6%), and papillary DCIS (n = 2/3.4%). Only two patients were ER negative (both IPC). HER-2 Neu was positive in 3 patients only, out of which 2 died of progressive disease (one EPC and one IPC). LN metastasis was present in 3 (5%) patients (one in each of 1st three types) and only one died of bone metastasis that was also Her-2Neu positive. All patients underwent upfront surgery except two patients who had synchronous IDC on the contralateral side. Breast conservation surgery (BCS) was performed in 34 (58.6%) and mastectomy in 22 (37.9%) patients. 13 patients did not undergo invasive axillary staging; the rest of 43 (74%) patients did (32 sentinel biopsy and 11 axillary dissection). Chemotherapy was given to 18 patients (31%), mostly to IPC (n = 12). Only 2 patients had bone metastasis (one was IPC and one EPC). Cancer-related death was observed in 3 patients. For all groups combined, 5-year OS was 98% and DFS was 92%. Conclusion: Overall, papillary carcinoma of the breast has an excellent prognosis, even though less intense treatment modalities were used. It is still difficult to define the optimum management and avoid overtreatment, given the limited data in the literature.

A new bioactive cocrystal of coumarin-3-carboxylic acid and thiourea: detailed structural features and biological activity studies.

Cocrystallization is a phenomenon widely used to enhance the biological and physicochemical properties of active pharmaceutical ingredients (APIs). The present study deals with the synthesis of a cocrystal of coumarin-3-carboxylic acid (2-oxochromene-3-carboxylic acid, C10H6O4), a synthetic analogue of the naturally occurring antioxidant coumarin, with thiourea (CH4N2S) using the neat grinding method. The purity and homogeneity of the coumarin-3-carboxylic acid-thiourea (1/1) cocrystal was confirmed by single-crystal X-ray diffraction, FT-IR analysis and thermal stability studies based on differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Detailed geometry analysis via density functional theory (DFT) demonstrated that the 1:1 cocrystal stoichiometry is sustained by N-H...O hydrogen bonding between the amine (-NH2) groups of thiourea and the carbonyl group of coumarin. The synthesized cocrystal exhibited potent antioxidant activity (IC50 = 127.9 ± 5.95 µM) in a DPPH radical scavenger assay in vitro in comparison with the standard N-acetyl-L-cysteine (IC50 = 111.6 ±â€…2.4 µM). The promising results of the present study highlight the significance of cocrystallization as a crystal engineering tool to improve the efficacy of pharmaceutical ingredients.

High antibiotic resistance and mortality with Acinetobacter species in a tertiary hospital, Nepal.

SETTING: Nepal Mediciti Hospital, Bhainsepati, Lalitpur, Nepal. OBJECTIVES: To determine antimicrobial resistance patterns, and the number and proportion of multidrug-resistant (MDR-) and extensively drug-resistant (XDR-) cases among all patients with Acinetobacter isolates between September 2018 and September 2019. DESIGN: This was a hospital laboratory-based, cross-sectional study. RESULTS: Acinetobacter spp. (n = 364) were more common in respiratory (n = 172, 47.3%) and invasive samples such as blood, body fluids (n = 95, 26.1%). Sensitivity to AWaRe (Access, Watch and Reserve) Group antibiotics (tigecycline, polymyxin B, colistin) remained high. MDR (resistance to at least three classes of antimicrobial agents) (n = 110, 30.2%) and XDR (MDR plus carbapenem) (n = 87, 23.9%) isolates were most common in the Watch Group of antibiotics and found in respectively 99 (31.0%) and 78 (24.5%) patients (n = 319). Infected patients were more likely to be aged >40 years (n = 196, 61.4%) or inpatients (n = 191, 59.9%); 76 (23.8%) patients had an unfavourable outcome, including death (n = 59, 18.5%). CONCLUSION: A significant proportion of MDR and XDR isolates was found; nearly one patient in five died. Robust hospital infection prevention and control measures (particularly for respiratory and invasive procedures) and routine surveillance are needed to reduce infections and decrease the mortality rate. Tigecycline, polymyxin B and colistin should be cautiously used only in MDR and XDR cases.

CONTEXTE: Hôpital de Mediciti, Bhainsepati, Lalitpur, Népal. OBJECTIFS: Déterminer les profils de résistance antimicrobienne, le nombre et la proportion de cas multirésistants (MDR) et ultrarésistants (XDR) parmi tous les patients chez qui des isolats d'Acinetobacter ont été identifiés de septembre 2018 à septembre 2019. MÉTHODE: Il s'agissait d'une étude transversale réalisée dans un laboratoire hospitalier. RÉSULTATS: Acinetobacter spp. (n=364) étaient plus fréquentes dans les échantillons respiratoires (n=172, 47,3%) et invasifs comme le sang et les fluides corporels (n=95, 26,1%). La sensibilité aux antibiotiques de la classification AWaRe (« dont l'accessibilité est essentielle ¼, « à utiliser sélectivement ¼, « de réserve ¼) (tigécycline, polymyxine B, colistine) restait élevée. Les isolats MDR (résistance à au moins trois classes d'agents antimicrobiens) (n=110, 30,2%) et XDR (MDR plus carbapénème) (n=87, 23,9%) étaient plus fréquents dans le groupe des « antibiotiques à utiliser sélectivement ¼ ; ils ont été observés chez respectivement 99 (31,0%) et 78 (24,5%) patients (n=319). Les patients infectés étaient plus susceptibles d'être âgés > 40 ans (n=196, 61,4%) ou hospitalisés (n=191, 59,9%). Un résultat défavorable a été observé chez 76 (23,8%) patients, dont des décès (n=59, 18,5%). CONCLUSION: Une proportion significative d'isolats MDR et XDR a été observée ; près de un patient sur cinq est décédé. Des mesures concrètes de prévention et de contrôle des infections à l'hôpital (notamment pour les procédures invasives et respiratoires) et de surveillance de routine sont nécessaires pour réduire les infections et diminuer le taux de mortalité. La tigécycline, la polymyxine B et la colistine doivent être utilisées avec prudence, uniquement en cas de MDR et XDR.

Population structure and genetic diversity of invasive Fall Armyworm after 2 years of introduction in India.

Fall Armyworm (FAW), Spodoptera frugiperda, is a polyphagous pest capable of feeding over 80 plant species and was indigenous to the Western Hemisphere. Within a span of 4 years, FAW has established itself throughout most of the regions in Africa and Asia causing significant losses in maize production. Owing to its revamped distribution range, it would be prudent to analyze the ensuing genetic changes and study the emerging phylogeographic patterns across the world. In this regard, we would like to provide a current snapshot of genetic diversity of FAW in India 2 years after the initial introduction and compare it with the worldwide diversity in order to trace the origins and evolutionary trajectories of FAW in India. We have investigated around 190 FAW samples from different regions in India for strain identity and polymorphism analysis on the basis of partial mitochondrial cytochrome oxidase I (COI) gene sequences. Apart from the ancestral rice and corn strain haplotype, our study demonstrates the presence of 14 more haplotypes unique to India at a haplotype diversity of 0.356. We were also able to record inter-strain hybrid haplotypes of rice and corn strains in India. Regional heterogeneity within Indian populations seems to be quite low representative of extensive migration of FAW within India. Distribution analysis of pairwise differences and rejection of neutrality tests suggest that the FAW population in India might be undergoing expansion. Our data is consistent with the findings suggesting a recent and common origin for invasive FAW populations in Asia and Africa, and does not indicate multiple introductions to India. This study reports the highest genetic diversity for Indian FAW populations to date and will be useful to track the subsequent evolution of FAW in India. The findings would have important ramifications for FAW behavior and composition throughout the world.

Exploration of a New Source of Sustainable Nanomaterial from the Koh-e-Suleiman Mountain Range of Pakistan for Industrial Applications.

The present study aimed to explore a new source of montmorillonite and to develop an extraction and purification protocol for its isolation from raw clay samples acquired from the Koh-e-Suleiman mountain range in Pakistan. The process involved the collection of raw clay from the source, identification and quantification of montmorillonite. Granulometric extraction and purification protocols increased the montmorillonite content from 21.8-25.1% in the raw clay to 90.1-93.9% after small-scale extraction and 85.33-89.33% on a larger scale. A techno-economic analysis highlighted the practicality and economic benefits of large-scale extraction for industrial applications. This study highlights the existence of a substantial new source of this valuable clay which is currently used across multiple industries including construction, pottery making, pharmaceuticals, cosmetics and engineering. It is intuitively expected that the large-scale extraction of the material will improve the economic condition of the region by providing employment opportunities to locals and may be a valuable resource for export.

Quality criteria for groundwater use from a rural part of Wanaparthy District, Telangana State, India, through ionic spatial distribution (ISD), entropy water quality index (EWQI) and principal component analysis (PCA).

The present study region comprises granite and granite gneisses aquifer system constituted by Precambrian rocks. Groundwater is the primary source for drinking and other domestic purposes. Many developing regions in the world suffer from lack of safe drinking water. A rural part of Wanaparthy District in Telangana State, India, is one of them. For this reason, the groundwater samples collected from the study region were analyzed for pH, TDS, Ca2+, Mg2+, Na+, K+, HCO3-, Cl-, SO42-, NO3- and F- and evaluated groundwater quality criteria, using ionic spatial distribution (ISD), entropy water quality index (EWQI) and principal component analysis (PCA). The ISD maps show that some locations are not suitable for drinking purpose due to exceeding concentrations of TDS, Mg2+, Na+, K+, HCO3-, Cl-, NO3-and F-, compared to those with national drinking water quality standards. According to the EWQI, about 3%, 47%, 43% and 7% of the total area come under the excellent, good, medium and extremely poor water quality types for drinking purpose, respectively. Chadha's diagram classified the area as carbonate hardness (63%), non-carbonate alkali (17%), carbonates alkali (13%) and non-carbonate hardness (7%) zones. The binary diagrams (Na+ + K+ vs TC, Na+ vs Ca2+ and HCO3- vs TC) indicate that the quality of groundwater is controlled by influences of water-rock interactions, mineral weathering and dissolution, ion exchange and evaporation as well as the impact of anthropogenic sources. The PCA transferred the chemical variables into three principal components accounts for about 81% of the total variance. The high positive loadings of PC1 (Cl-, TDS, SO42-, Na+, NO3-, Mg2+ and HCO3-) stand for processes of silicate weathering and dissolution, ion exchange and evaporation, and the influence of domestic waste waters, irrigation return flows and chemical fertilizers on the groundwater system, the PC2 (F- and pH) signifies the alkaline nature of groundwater, which causes fluorosis, and the PC3 (K+) is a result of potassium fertilizers. The study helps to take remediate measures at a specific site and hence suggests the treatment of water before its drinking and also the recharge of the aquifer artificially to improve the groundwater quality.

Double-level fixator-assisted nailing (DL-FAN).

AIMS: Double-level lengthening, bone transport, and bifocal compression-distraction are commonly undertaken using Ilizarov or other fixators. We performed double-level fixator-assisted nailing, mainly for the correction of deformity and lengthening in the same segment, using a straight intramedullary nail to reduce the time in a fixator. PATIENTS AND METHODS: A total of 23 patients underwent this surgery, involving 27 segments (23 femora and four tibiae), over a period of ten years. The most common indication was polio in ten segments and rickets in eight; 20 nails were inserted retrograde and seven antegrade. A total of 15 lengthenings were performed in 11 femora and four tibiae, and 12 double-level corrections of deformity without lengthening were performed in the femur. The mean follow-up was 4.9 years (1.1 to 11.4). Four patients with polio had tibial lengthening with arthrodesis of the ankle. We compared the length of time in a fixator and the external fixation index (EFI) with a control group of 27 patients (27 segments) who had double-level procedures with external fixation. The groups were matched for the gain in length, age, and level of difficulty score. RESULTS: The mean gain in length was statistically similar in the two groups: 3.9 cm (1.5 to 9.0) in the study group and 4.2 cm (3.4 to 5.0) in the control group (p = 0.350). The mean time in a fixator was significantly less in the study group compared with the control group: 8.6 weeks (2.0 to 22.8) versus 30.2 weeks (25.0 to 35.4; p < 0.001). The mean EFI was significantly lower in the study group compared with the control group: 17.7 days/cm (10.6 to 35.6) versus 73.4 days/cm (44.5 to 102.3; p < 0.001). The ASAMI (Association for the Study and Application of the Method of Ilizarov) bone score was excellent in 22, good in four, and fair in one. The ASAMI functional score was excellent in 20 and good in seven. There were no infections, superficial or deep. CONCLUSION: Double-level osteotomies or two procedures using a custom-made straight nail and external fixation can be used to correct deformities or to treat nonunion or malunion and may be combined with arthrodesis of the ankle with lengthening. It is a reasonably safe procedure that allows accurate and cost-effective treatment with a relatively short time in a fixator.

Seroprevalence of Bluetongue Virus in small ruminants in Balochistan province, Pakistan.

Bluetongue (BT), caused by bluetongue virus (BTV), is a vector-borne disease of small ruminants that has the potential to spread across international borders. Despite large populations of susceptible animals and borders with BTV endemic countries, little is known of the disease burden and prevalent serotypes in the province of Balochistan in Pakistan. We conducted a cross-sectional study to determine seroconversion and prevalent serotypes in selected districts of the province using a competitive enzyme-linked immunosorbent assay (cELISA) and real-time polymerase chain reaction (RT-PCR). Sera (n = 876) were collected from clinically healthy sheep and goats originating from the districts of Quetta (n = 300), Mastung (n = 201), Killa Saifullah (n = 75) and Kech (n = 300). None of the study herds (n = 97) were seronegative for BTV, and at the individual level, the overall prevalence of BTV seroconversion was 47.26% (n = 414/876, 95% CI = 43.92%-50.63%). A higher percentage of goats (50.87%, 95% CI = 45.99%-55.73%) were seropositive for anti-VP7 immunoglobulins (IgG) than sheep (44.21%, 95% CI = 39.81%-48.70%). Odds ratios of seroconversion for goats were associated with breed type (χ2  = 16.84, p = .01), parity (χ2  = 23.66, p = .00) and presence of vector (χ2  = 2.63, p = .10), whereas for sheep, it was associated with breed type (χ2  = 13.80, p = .01) and parity (χ2  = 53.40, p = .00). Serotype 8 was the most prevalent (26.82%, 95% CI = 14.75%-43.21%) followed by an equal prevalence of serotypes 2 and 9 (7.31%, 95% CI = 1.91%-21.01%). To the best of our knowledge, this is the first study conducted in Balochistan province and the results indicate that there is a necessity to initiate intervention strategies to control BT disease burden not only in this region of Pakistan but also in adjacent areas of the neighbouring countries, Iran and Afghanistan.

Pattern of Corneal Diseases in Paediatric Age Group at a Tertiary Eye Care Center in Nepal.

OBJECTIVE: It is to study the pattern of corneal diseases (including injuries) in paediatric population in a tertiary eye care center. MATERIALS AND METHODS: A descriptive, cross sectional study was carried out in a tertiary eye care center which included 176 cases. RESULTS: Out of 176 cases studied, 6 cases (3.4%) presented with congenital causes, 4 cases (2.27%) were of dystrophy and ectasia, 63 cases (35.79%) had infective origin, 17 cases (9.65%) had inflammatory cause, 9 cases (5.11%) had systemic association and 77 cases (43.75%) had traumatic causes. CONCLUSION: Trauma was noted to be the most important cause for corneal diseases in paediatric population followed by infective conditions. Viral keratitis was found to be the most common type of corneal infection in the paediatric age group.

A radiographic study estimating age of mandibular third molars by periodontal ligament visibility.

BACKGROUND: Visibility of the periodontal ligament of mandibular third molars (M3) has been suggested as a method to estimate age. AIM: To assess the accuracy of this method and compare the visibility of the periodontal ligament in the left M3 with the right M3. The sample was archived panoramic dental radiographs of 163 individuals (75 males, 88 females, age 16-53 years) with mature M3's. MATERIALS AND METHODS: Reliability was assessed using Kappa. Accuracy was assessed by subtracting chronological age from estimated age for males and females. Stages were cross-tabulated against age stages younger than and at least 18 and 21 years of age. Stages were compared in the left M3 and right M3. RESULTS: Analysis showed excellent intra-observer reliability. Mean difference between estimated and chronological ages was 7.21 years (SD 5.16) for left M3 and 7.69 (SD 6.08) for right M3 in males and 6.87 (SD 5.83) for left M3 and 8.61 (SD 6.58) for right M3 in females. Minimum ages of stages 0 to 2 were younger than previously reported, despite a small sample of individuals younger than 18. The left and right M3 stage differed in 46% of the 85 individuals with readings from both side and estimated age differed from -10.5 to 12.2 years between left and right. CONCLUSION: Accuracy of this method was between 6 and 8 years with an error of 5 to 6 years. The number of individuals with mature M3 apices younger than 18 years was small. The stage of visibility of the periodontal ligament differed between left and right in almost half of our sample with both teeth present. Our findings question the use of this method to estimate age or to discriminate between age younger and at least 18 years.

Orange Peel Extracts: Chemical Characterization, Antioxidant, Antioxidative Burst, and Phytotoxic Activities.

The search for novel drugs and alternative medicine has led to increased research in medicinal plants. Among such plants is the orange fruit. Its peels have been utilized for long as an active ingredient in most traditional medicines. This study aims at investigating the chemical properties of the hexane and dichloromethane (DCM) extracts of orange peel as well as their biological potentials. Blended peels were extracted with n-hexane and n-dichloromethane, respectively. The resulting extracts were subjected to gas chromatography mass spectrometry (GCMS) characterization. The extracts were also assayed for free radical scavenging ability against 1,1 -diphenyl -2 picrylhydrazyl (DPPH), antioxidative burst via measuring luminol -amplified chemiluminescence response in human blood, and phytotoxicity against lemna minor. GCMS analysis revealed a predominance of fatty acid methyl esters in the hexane extract, while the DCM extract had more ketone metabolites. The DCM extract had significant (p < .05) higher free radical scavenging and antioxidative burst activities compared to the hexane. Both extracts revealed a significantly (p < .05) high phytotoxicity activity. Results from this study indicated that solvent type played a vital a role in the extraction of secondary metabolites, which are responsible for the observed biological activities. The higher activities by the DCM extract can be attributed to its constituents as revealed by GCMS analysis. There is great need to explore the phytotoxicity potentials of both extracts as natural herbicides.

Sensitive quantification of six steroidal lactones in Withania coagulans extract by UHPLC electrospray tandem mass spectrometry.

A method for the concurrent determination of six known steroidal lactones (syn. withanolides or withasteroids), namely withaferin A, withanolide H, withanolide K, withanolide A, withacoagulin H, and withanolide J in Withania coagulans extracts was developed. Extracts of Withania species and purified withanolides are considered among the most important natural products used for medicinal purposes. Methanolic extract of plant material was subjected to reverse phase ultra-high performance liquid chromatography (UHPLC) coupled with electrospray (JetStream ESI) triple quadrupole mass spectrometer operated in the Multiple Reaction Monitoring (MRM) mode. Satisfactory separation of withanolide component was achieved within 9 min on UHPLC runtime. The limits of detection (LOD) and the limits of quantitation (LOQs) for the six withanolides ranged between 0.040-4.80 ng/mL, and 0.13-16 ng/mL, respectively. Linear responses were attained for all six withanolides in two orders of magnitude with the linear regression coefficient values ⩾0.998. At the five QC levels inspected, the relative standard deviations (RSD) were found below 5% in most cases. The newly developed method is fast, precise, and sensitive, therefore, the method can be used for high-throughput quantification of various withanolides in W. coagulans extract, and other herbal formulations, derived from W. coagulans.

Analysis of an early intervention tibial component for medial osteoarthritis.

Tibial component loosening is an important failure mode in unicompartmental knee arthroplasty (UKA) which may be due to the 6-8 mm of bone resection required. To address component loosening and fixation, a new early intervention (EI) design is proposed which reverses the traditional material scheme between femoral and tibial components. The EI design consists of a plastic inlay for the distal femur and a thin metal plate for the proximal tibia. With this reversed materials scheme, the EI design requires minimal tibial bone resection compared with traditional UKA. This study investigated, by means of finite element (FE) simulations, the advantages of a thin metal tibial component compared with traditional UKA tibial components, such as an all-plastic inlay or a metal-backed onlay. We hypothesized that an EI tibial component would produce comparable stress, strain, and strain energy density (SED) characteristics to an intact knee and more favorable values than UKA components, due primarily to the preservation of dense cancellous bone near the surface. Indeed, FE results showed that stresses in the supporting bone for an EI design were close to intact, while stresses, strains, and strain energy densities were reduced compared with an all-plastic UKA component. Analyzed parameters were similar for an EI and a metal-backed onlay, but the EI component had the advantage of minimal resection of the stiffest bone.

Anticancer investigations on Carissa opaca and Toona ciliata extracts against human breast carcinoma cell line.

This study was aimed to determine the effectiveness of two ethnobotanically important plant species Carissa opaca and Toona ciliata against cancer cells. Antiproliferative activity of the plant extracts and their fractions was tested against MCF-7 breast cancer cell line using MTT assay. A concentration dependent inhibition was observed for both crude extracts. C. opaca crude extract showed 78.5% inhibition while T. ciliata showed 57% activity against cancer cells at 500 µg/mL. Fractions were tested at 200 µg/mL concentration and were more active than crude extracts. Chloroform fraction of C. opaca showed maximum inhibition 99% followed by ethyl acetate and methanol fraction of C. opaca exhibiting 96% and 94% inhibition, respectively. Ethyl acetate fraction of T. ciliata showed 78% inhibition of cancer cells at the same concentration. Preliminary phytochemical screening revealed the chemical composition of C. opaca extract containing alkaloids, flavonoids, tannins and saponins while T. ciliata had tannins and coumarins. Present investigation suggests that tested plant species possess potent anticancer compounds specially chloroform, ethyl acetate and methanol fractions of C. opaca and ethyl acetate fraction of T. ciliata can be an important source of anticancer drugs.

General practitioners' knowledge and approach to chronic kidney disease in Karachi, Pakistan.

Due to lack of adequate number of formally trained nephrologists, many patients with chronic kidney disease (CKD) are seen by general practitioners (GPs). This study was designed to assess the knowledge of the GPs regarding identification of CKD and its risk factors, and evaluation and management of risk factors as well as complications of CKD. We conducted a cross-sectional survey of 232 randomly selected GPs from Karachi during 2011. Data were collected on a structured questionnaire based on the kidney disease outcomes and quality initiative recommendations on screening, diagnosis, and management of CKD. A total of 235 GPs were approached, and 232 consented to participate. Mean age was 38.5 ± 11.26 years; 56.5% were men. Most of the GPs knew the traditional risk factors for CKD, i.e., diabetes (88.4%) and hypertension (80%), but were less aware of other risk factors. Only 38% GPs were aware of estimated glomerular filtration rate in evaluation of patients with CKD. Only 61.6% GPs recognized CKD as a risk factor for cardiovascular disease. About 40% and 29% GPs knew the correct goal systolic and diastolic blood pressure, respectively. In all, 41% GPs did not know when to refer the patient to a nephrologist. Our survey identified specific gaps in knowledge and approach of GPs regarding diagnosis and management of CKD. Educational efforts are needed to increase awareness of clinical practice guidelines and recommendations for patients with CKD among GPs, which may improve management and clinical outcomes of this population.

Thermal analysis of some natural polysaccharide materials by isoconversional method.

Isoconversional thermal analysis of some important polysaccharides from functional foods is reported. Various thermal parameters including apparent activation energy (Ea), pre-exponential factor (A) were worked out, and the fitness of data to different models describing the degradation kinetics of polysaccharides was studied. The polysaccharides from Mimosa pudica (MP), Plantago ovata (PO), Argyreia speciosa (AS), Acacia nilotica (AN), P. ovata husk (HK) and Acacia modesta (AM) exhibited multistep degradation while those from Astragalus gummifer (AG), Salvia aegyptiaca (SA) and Ocimum basicilicum (OB) degraded mainly in single step. Generally, the degradation was exothermal. The average Ea values as determined by Flynn-Wall-Ozawa method were found to be in the range 132-187 kJ mol(-1). The mean comprehensive index of thermal stability (ITS) fell in the range 0.33-0.43. All the materials under investigation except those from SA and AS appear to be as stable as some of the important commercial materials used as pharmaceutical ingredients. Model-fitting analysis revealed that the major degradation step follows first-order kinetics.

Lamellar ichthyosis presenting as bilateral spontaneous corneal perforation.

INTRODUCTION: Lamellar Ichthyosis is an autosomal recessive, inherited skin disorder characterized by thickening, fissuring and scaling of the skin. OBJECTIVE: To report a case of lamellar icthyosis and highlight the importance of monitoring corneal health in these patients. CASE: We report a rare case of bilateral spontaneous corneal perforation in a patient with lamellar ichthyosis .The patient presented with complaints of diminution of vision, foreign body sensation, watering and discharge in both of his eyes for the last three months followed by pain and redness for one week. Visual acuities were light perception in both the eyes. Cicatricial ectropion was seen in both the lower eyelids. Corneal perforation was seen in both the eyes. Lamellar ichthyosis was diagnosed on the basis of scaling and excessive dryness of the entire body skin and was confirmed by skin biopsy. Peneterating keratoplasty of both eyes was done with cataract surgery of the right. The systemic anti-ichthyosis therapy was started. Ectropion of the right eye was corrected, and on follow-up at three months, the patient had a visual acuity of 4 /60 and CFCF in the right and the left eye respectively. CONCLUSION: In patients with cicatricial ectropion and dry eye secondary to ichthyosis, corneal health should be closely monitored because of the perforation risk.

Geochemical assessment of metal concentrations in sediment core of Korangi Creek along Karachi Coast, Pakistan.

Sediment core from Korangi Creek, one of the polluted coastal locations along the Karachi Coast Pakistan, was collected to trace the history of marine pollution and to determine the impact of industrial activity in the area. Down core variation of metals such as Ca, K, Mg, Al, S, Ti, V, Cr, Mn, Fe, Ni, Cu and Zn was studied in the 72.0 cm core. Nuclear analytical techniques, proton induced X-rays emission (PIXE), was employed to ascertain the chemical composition in sediment core. Grain size analysis and sediment composition of cored samples indicated that Korangi creek sediments are clayey in nature. Correlation matrix revealed a strong association of Ni, Cu, Cr and Zn with Fe and Mn. To infer anthropogenic input, enrichment factor (EF), degree of contamination and pollution load index were calculated. EF showed severe enrichment in surface sediment for Ni, Cu, Cr and Zn, indicating increased industrial effluents discharge in recent years. The study suggests that heavy metal discharge in the area should be regulated. If the present trend of enrichment is allowed to continue unabated, it is most likely that the local food web complexes in the creek might be at highest risk.