Advances in Nanocarriers for Effective Delivery of Docetaxel in the Treatment of Lung Cancer: An Overview.

Docetaxel (DCX) is a highly effective chemotherapeutic drug used in the treatment of different types of cancer, including non-small cell lung cancer (NSCLC). The drug is known to have low oral bioavailability due to its low aqueous solubility, poor membrane permeability and susceptibility to hepatic first-pass metabolism. To mitigate these problems, DCX is administered via the intravenous route. Currently, DCX is commercially available as a single vial that contains polysorbate 80 and ethanol to solubilize the poorly soluble drug. However, this formulation causes short- and long-term side effects, including hypersensitivity, febrile neutropenia, fatigue, fluid retention, and peripheral neuropathy. DCX is also a substrate to the drug efflux pump P-glycoprotein (P-gp) that would reduce its concentration within the vicinity of the cells and lead to the development of drug resistance. Hence, the incorporation of DCX into various nanocarrier systems has garnered a significant amount of attention in recent years to overcome these drawbacks. The surfaces of these drug-delivery systems indeed can be functionalized by modification with different ligands for smart targeting towards cancerous cells. This article provides an overview of the latest nanotechnological approaches and the delivery systems that were developed for passive and active delivery of DCX via different routes of administration for the treatment of lung cancer.

Correction to: Screening and computational analysis of colorectal associated non-synonymous polymorphism in CTNNB1 gene in Pakistani population.

Following publication of the original article [1], the authors have flagged that the article has published with an error in the order of the affiliations.

Prenatal BPA and its analogs BPB, BPF, and BPS exposure and reproductive axis function in the male offspring of Sprague Dawley rats.

Research in the past has indicated associated long-term and low levels of exposure of bisphenol A (BPA) in early life and neuroendocrine disorders, such as obesity, precocious puberty, diabetes, and hypertension. BPA and its analogs bisphenol B (BPB), bisphenol F (BPF), and bisphenol S (BPS) have been reported to have similar or even more toxic effect as compared to BPA. Exposure of rats to BPA and its analogs BPB, BPF, and BPS resulted in decreased sperm production, testosterone secretion, and histological changes in the reproductive tissues of male rats. In the present study, BPA, BPB, BPF, and BPS were administered in drinking water at concentrations of (5, 25, and 50 µg/L) from pregnancy day (PD) 1 to PD 21. Body weight (BW), hormonal concentrations, antioxidant enzymes, and histological changes were determined in the reproductive tissues. BPA and its analogs prenatal exposure to female rats induced significant statistical difference in the antioxidant enzymes, plasma testosterone, and estrogen concentrations in the male offspring when compared with the control. Histological parameters of both testis and epididymis revealed prominent changes in the reproductive tissues. The present study suggests that BPA and its analogs BPB, BPF, and BPS different concentrations led to marked alterations in the development of the male reproductive system.

Determining the cause of stillbirth in Kumasi, Ghana.

OBJECTIVE: To classify cause-of-death (COD) for stillbirths occurring in a major referral hospital in Kumasi, Ghana. METHODS: In a retrospective review conducted between June 8, 2011, and June 12, 2012, detailed information was collected on all stillbirths delivered at Komfo Anokye Teaching Hospital in Kumasi, Ghana. Patient records were independently reviewed by investigators using the Perinatal Society of Australia and New Zealand's Perinatal Death Classification system to determine COD for each case. RESULTS: COD was analyzed in 465 stillbirth cases. The leading causes of death were hypoxic interpartum death (105, 22.6%), antepartum hemorrhage (67, 14.4%), hypertension (52, 11.2%), and perinatal infection (32, 6.9%). One hundred and fifty seven (33.8%) stillbirths were classified as unexplained antepartum deaths. CONCLUSIONS: This evaluation of stillbirth in a busy, tertiary care hospital in Kumasi, Ghana provides crucial insight into the high volume of stillbirth in Ghana as well as its medical causes. The study demonstrated the high rate of stillbirth attributed to hypoxic intrapartum events, placental abruption, pre-eclampsia, and unspecified bacterial infections. Yet, our rate of unexplained stillbirths underscores the need for a stillbirth classification system that thoughtfully integrates the needs and limitations of low-resource settings as unexplained stillbirth rates are a common indicator of the effectiveness of a classification system.

Managing adolescent pregnancy: The unique roles and challenges of private general practitioners in Malaysia.

INTRODUCTION: Managing adolescent pregnancy in the primary care setting is complex, as it requires doctors to navigate through a combination of medical, social, financial and legal needs. Objective: This study explores the perspectives of private general practitioners on their roles and challenges in managing adolescent pregnancy in Malaysia. METHODS: Nineteen private general practitioners in Selangor and Kuala Lumpur participated in in-depth interviews in 2015. A topic guide was used for interview navigation. Participants were asked to discuss their experiences and approaches in managing pregnant adolescents. We used purposive sampling to recruit consenting private general practitioners who had experience in managing adolescent pregnancy. The verbatim transcripts of the audio-recorded interviews were analyzed using thematic analysis. Data reached saturation at the nineteenth in-depth interview. Results: Two themes emerged. Under the theme 'inadvertent advocator,' participants described their tasks with regards to building trust, calming angry parents and delivering comprehensive counseling and care related to the sexual and reproductive health of adolescents, including requests for abortions. Theme two, 'challenges of private general practitioners,' refers mainly to personal and religious conflicts arising from a request for an abortion and deficiencies in support and multidisciplinary integration within their practice settings. CONCLUSION: General practitioners practicing in the private sector identify themselves as active players in supporting pregnant adolescents but face many challenges arising from the personal, religious, professional and community levels. Addressing these challenges is important for optimal care delivery to pregnant adolescents in this community.

Genetic Modifiers of Fetal Haemoglobin (HbF) and Phenotypic Severity in ß-Thalassemia Patients.

BACKGROUND: The phenotypic severity of ß-thalassemia is highly modulated by three genetic modifiers: ß-globin (HBB) mutations, co-inheritance of α-thalassemia and polymorphisms in the genes associated with fetal haemoglobin (HbF) production. This study was aimed to evaluate the effect of HbF related polymorphisms mainly in the HBB cluster, BCL11A (B-cell CLL/lymphoma 11A) and HBS1L-MYB (HBS1-like translational GTPase-MYB protooncogene, transcription factor) with regards to clinical severity. METHODS: A total of 149 patients were included in the study. HBA and HBB mutations were characterised using multiplex PCR, Sanger sequencing and multiplex ligationdependent probe amplification. In addition, 35 HbF polymorphisms were genotyped using mass spectrometry and PCR-restriction fragment length polymorphism (PCRRFLP). The genotype-phenotype association was analysed using SPSS version 22. RESULTS: Twenty-one HBB mutations were identified in the study population. Patients with HBB mutations had heterogeneous phenotypic severity due to the presence of other secondary modifiers. Co-inheritance of α-thalassemia (n = 12) alleviated disease severity of ß-thalassemia. In addition, three polymorphisms (HBS1LMYB, rs4895441 [P = 0.008, odds ratio (OR) = 0.38 (0.18, 0.78)], rs9376092 [P = 0.030, OR = 0.36 (0.14, 0.90)]; and olfactory receptor [OR51B2] rs6578605 [P = 0.018, OR = 0.52 (0.31, 0.89)]) were associated with phenotypic severity. Secondary analysis of the association between single-nucleotide polymorphisms with HbF levels revealed three nominally significant SNPs: rs6934903, rs9376095 and rs9494149 in HBS1L-MYB. CONCLUSION: This study revealed 3 types of HbF polymorphisms that play an important role in ameliorating disease severity of ß-thalassemia patients which may be useful as a predictive marker in clinical management.

Feasibility of Implementing Chronic Care Model in the Malaysian Public Primary Care Setting.

INTRODUCTION: Non-communicable diseases (NCD) is a global health threat. the Chronic Care Model (CCM) was proven effective in improving NCD management and outcomes in developed countries. Evidence from developing countries including Malaysia is limited and feasibility of CCM implementation has not been assessed. this study intends to assess the feasibility of public primary health care clinics (PHC) in providing care according to the CCM. METHODOLOGY: A cross-sectional survey was conducted to assess the public PHC ability to implement the components of CCM. All public PHC with Family Medicine Specialist in Selangor and Kuala Lumpur were invited to participate. A site feasibility questionnaire was distributed to collect site investigator and clinic information as well as delivery of care for diabetes and hypertension. RESULTS: there were a total of 34 public PHC invited to participate with a response rate of 100%. there were 20 urban and 14 suburban clinics. the average number of patients seen per day ranged between 250-1000 patients. the clinic has a good mix of multidisciplinary team members. All clinics had a diabetic registry and 73.5% had a hypertensive registry. 23.5% had a dedicated diabetes and 26.5% had a dedicated hypertension clinic with most clinic implementing integrated care of acute and NCD cases. DISCUSSION: the implementation of the essential components of CCM is feasible in public PHCs, despite various constraints. Although variations in delivery of care exists, majority of the clinics have adequate staff that were willing to be trained and are committed to improving patient care.

Early Vessels Exploration of Pink Pulseless Hand in Gartland III Supracondylar Fracture Humerus in Children: Facts and Controversies.

The management of pink pulseless limbs in supracondylar fractures has remained controversial, especially with regards to the indication for exploration in a clinically well-perfused hand. We reviewed a series of seven patients who underwent surgical exploration of the brachial artery following supracondylar fracture. All patients had a non-palpable radial artery, which was confirmed by Doppler ultrasound. CT angiography revealed complete blockage of the artery with good collateral and distal run-off. Two patients were more complicated with peripheral nerve injuries, one median nerve and one ulnar nerve. Only one patient had persistent arterial constriction which required reverse saphenous graft. The brachial arteries were found to be compressed by fracture fragments, but were in continuity. The vessels were patent after the release of obstruction and the stabilization of the fracture. There was no transection of major nerves. The radial pulse was persistently present after 12 weeks, and the nerve activity returned to full function.

Obestatin modulates ghrelin's effects on the basal and stimulated testosterone secretion by the testis of rat: an in vitro study.

The functional antagonism between obestatin and ghrelin in the testis is under investigation. We investigated the ability of obestatin to counteract the inhibitory effect of ghrelin on basal and stimulated testosterone (T) secretion in vitro. Testicular strips from adult rats were incubated with 10 ng/ml and 100 ng/ml of obestatin alone, ghrelin alone and obestatin + ghrelin. Obestatin modulation of stimulated T secretion was evaluated by incubation of testicular samples with 10 ng/ml and 100 ng/ml obestatin, ghrelin and obestatin + ghrelin in the absence and presence of 10 IU of human chorionic gonadotrophin (hCG). T concentrations in the hCG treated groups were significantly (P<0.0001) higher than those in the control groups. Obestatin caused a significant increase in basal T secretion in a dose-dependent manner; however, obestatin at the both 10 ng/ml and 100 ng/ml significantly (P<0.0001) increased hCG-stimulated T secretion. In contrast, ghrelin in a dose-dependent manner significantly (P<0.001) decreased both basal and hCG-induced T secretion by testicular slices. Obestatin opposed the inhibitory effect of ghrelin on T secretion under both basal and hCG-stimulated conditions at all doses tested. In conclusions, administration of obestatin was able to antagonize the inhibitory effect of ghrelin on testosterone secretion in vitro.

Early Vessels Exploration of Pink Pulseless Hand in Gartland III Supracondylar Fracture Humerus in Children: Facts and Controversies

The management of pink pulseless limbs in supracondylar fractures has remained controversial, especially with regards to the indication for exploration in a clinically well-perfused hand. We reviewed a series of seven patients who underwent surgical exploration of the brachial artery following supracondylar fracture. All patients had a non-palpable radial artery, which was confirmed by Doppler ultrasound. CT angiography revealed complete blockage of the artery with good collateral and distal run-off. Two patients were more complicated with peripheral nerve injuries, one median nerve and one ulnar nerve. Only one patient had persistent arterial constriction which required reverse saphenous graft. The brachial arteries were found to be compressed by fracture fragments, but were in continuity. The vessels were patent after the release of obstruction and the stabilization of the fracture. There was no transection of major nerves. The radial pulse was persistently present after 12 weeks, and the nerve activity returned to full function.

Assessment of "fresh" versus "macerated" as accurate markers of time since intrauterine fetal demise in low-income countries.

OBJECTIVE: To compare provider assessment of fetal maceration with death-to-delivery interval to evaluate the reliability of appearance as a proxy for time of death. METHODS: Cohort chart abstraction was performed for all stillbirth deliveries at or above 28 weeks of gestation during a 1-year period in a teaching hospital in Ghana. RESULTS: Of 470 stillborn infants, 337 had adequate data for analysis. Of 47 fetuses alive on admission with death-to-delivery intervals estimated to be less than 8 hours (expected to be reported as fresh), 14 (30%) were actually reported as macerated. Of 94 cases in which the fetus was deceased on admission with death-to-delivery interval of more than 8 hours (expected to be macerated), 17 (18%) were described as fresh. CONCLUSION: Provider description of fetal appearance may be an unreliable indicator for time since fetal death. The findings have significant implications for stillbirth prevention and assessment.

Study of aerobic bacterial conjunctival flora in patients with diabetes mellitus.

INTRODUCTION: Normal bacterial flora may be altered by a variety of factors. OBJECTIVE: To study the aerobic bacterial conjunctival flora in patients with diabetes mellitus and to find its clinical significance by comparing the results to the conjunctival flora of non-diabetic subjects. MATERIALS AND METHODS: A total of 75 diabetic patients were included as cases and 25 nondiabetics as controls to compare the results. Specimens for the study of conjunctival flora were taken by rubbing sterile cotton-tipped swabs to the inferior palbebral conjunctiva. The conjunctival culture report of the patients with diabetic mellitus was compared to that of nondiabetic subjects. RESULTS: Positive conjunctival cultures were seen in a higher percentage of patients with diabetes (unilateral and bilateral positive conjunctival cultures 34.66 % and 58.66 % respectively) compared to that in non-diabetic controls (unilateral and bilateral positive conjunctival cultures 24 % and 16 % respectively). Diabetics showed a higher proportion of coagulase negative staphylococci (45.33 %), compared to the non-diabetic group (16 %). Among the diabetic patients, positive conjunctival cultures were detected more frequently in those with diabetic retinopathy compared to those without retinopathy. A higher proportions of bilateral positive conjunctival cultures were seen in cases with proliferative diabetic retinopathy (38.63 %) in comparison to patients with no retinopathy and different stages of non-proliferative diabetic retinopathy. CONCLUSION: The conjunctival floral pattern with increased bacteria in diabetics is a predominant cause of many diabetes-related ocular infections. The presence of diabetic retinopathy is an indicator for increased colonization of conjunctiva, and its severity correlates with the severity of diabetic retinopathy.

Anti-HCMV IgG positivity rate among renal transplant recipients in Baghdad.

In developing countries, the majority of infection by human cytomegalovirus (HCMV) occurs during childhood and continues as a latent infection. By adulthood, almost all the population may show anti-HCMV IgG as positive. This study was undertaken to determine the correlation between the prevalence of HCMV antibodies and HCMV infection during post transplant period among renal transplant patients in Baghdad. 43 renal transplant patients attending three renal transplantation centers, and 40 healthy individuals who served as controls were enrolled in this study. 18 (41.9%) were transplanted recently and they were under post-operative follow-up and 25 (58.1%) were transplanted more than one year ago. Detection of anti-HCMV IgG was carried out using enzyme-linked immunosorbant assay (ELISA). The results revealed that anti-HCMV IgG was significantly higher among renal transplant recipients compared to healthy controls (97.7% vs 85%, P = 0.04). The anti-HCMV IgG positivity rate was not affected by patients' age, sex, and duration after transplantation or immunosuppressive therapy. We conclude that the high anti-HCMV IgG positivity rate among Iraqi renal transplant recipients make them prone to considerable risk of reactivation of HCMV infection.

The effect of Piper betel extract on the wound healing process in experimentally induced diabetic rats.

BACKGROUND: Piper betel (PB) possesses antimicrobial, antifungal, antioxidant and wound healing properties due to its powerful antioxidant effect. Diabetes mellitus (DM) is a metabolic disorder which is associated with complications like impaired wound healing, nephropathy and neuropathy. The main aim of the study was to study the wound healing properties of PB. MATERIALS AND METHODS: A total of 33 male Sprague-Dawley rats (250-300 g) were taken and divided into 3 groups: Group I (control) comprising of 14 rats; Group II (diabetic untreated) comprising of 9 rats; Group III (diabetic treated) comprising of 10 rats. After 10 days of acclimatization, the animals were fasted overnight and diabetes was induced by administration of streptozotocin (45 mg/Kg body weight in a single dose, through tail vein) to group II and III animals. Four 6 mm-diameter full thickness skin excision wounds were created and PB extract (50 mg diluted in 0.1 ml of normal saline) was applied locally for 10 days in group III. The group I and II received normal saline (0.1 ml) for 10 days. The total protein content and the wound contraction rate were determined. RESULTS: The wound contraction rate of group III (35.03 +/- 2.96) was higher as compared to group II (18.40 +/- 3.87) with p = 0.014. The total protein content for group III was 106.39 +/- 4.46 as compared to group II (72.86 +/- 12.86) with p = 0.050. CONCLUSION: PB acted as a protective agent in the early phase of wound healing by increasing total protein content and wound contraction rate.

Efficacy of some oils and chemical compounds on Insignorthezia insignis (Browne) (Hemiptera: Ortheziidae) infesting Lantana camara in Alexandria, Egypt.

Field and laboratory experiments were conducted in March, 2008 in El-Nouzha garden, Alexandria governorate. Pre-and post treatment inspections of the insects were examined and recorded before and after (2,4,8, and 12 weeks). Spraying was applied to evaluate the efficiency of the tested compounds, [Mineral oils (KZ oil and Star oil); IGRs (Chlorfluazuron, lufenuron and pyriproxyfen); Neem oil; emamectin benzoate and thiamethoxam]. Percentages of reduction were calculated. The ensign scale insects Insignorthezia insignis (Browne) were collected from treated Lantana camara shrubs to investigate the effect of the tested chemicals on Aspartate transferase (AST), Alanine transferase (ALT) and Alkaline-phosphatase (ALPK) of the insect enzymes activities. From the obtained results, it could be concluded that the tested materials gave good results for controlling both adult and immature stages of the ensign scale insect Insignorthezia insignis (Browne) that infested Lantana camara shrubs, through affecting enzymes activities of the assigned insect pest.

Comparative analysis of three scale insect species populations (Hemiptera: Coccoidea: Diaspididae) and their parasitoid, Aphytis diaspidis(Howard) on pear trees in Burg el-Arab area, Alexandria, Egypt.

The infestation abundance of each of the inspected scale insect species: San Jose scale, Diaspidiotus perniciosus (Comstock), Greedy scale, Hemiberlisio rapax (Comstock) and Olive scale, Parlatoria oleae (Cloveé) on pear trees, more or less varied as the months of each growing season differed. The comparative abundance percentages in both seasons of 2004-2005 and 2005-2006 were (51.80 and 51.40), (41.20 and 40.90) and (7.10 and 7.70) of the counted individuals of the grand total of H. rapax, D. perniciosus and P. oleae, in respect. In other words, the Greedy scale (GS) was the highly abundant scale followed by the San Jose scale (SJS), but the olive scale represented the lowest one. The more or less increased and/or decreased abundance of each of the investigated scale insect species pointed to the existence of three overlapping generations throughout the season which were characterized by fluctuating peaks of population densities of the studied pests during the months of each annual season: autumn, winter, spring and summer.

Controversies in congenital clubfoot : literature review.

Despite common occurrence, congenital talipes equinovarus (clubfoot) is still a subject of controversy. It poses a significant problem with its unpredictable outcome, especially when the presentation for treatment is late. The true etiology remains unknown although many theories have been put forward. A standard management scheme is difficult as there is no uniformity in the pathoanatomy, classification and radiographic evaluation. These differ according to the age of the child and the severity of the condition. The paper discusses these controversies with an emphasis on the proposed etiologies and types of treatment performed.

The population dynamics of Fiorinia fioriniae (Targioni) (Homoptera: Diaspididae) and factors affecting its seasonal abundance in Egypt.

Fiorinia fioriniae (Targioni) was observed attacking Callistemon lanceolatus at the Experimental Farm of the Agricultural Research Station and Ruscus hypoglossum at Antoniades park in Alexandria Governorate; Egypt. The infestation rate on Ruscus hypoglossum, reached its maximum (98.0%) during autumn months, while the minimum rate 68.3%, was recorded during summer months. The fluctuating population density of F. fioriniae showed three distinct peaks. The first peak of 731.0 individuals/10 branches was recorded in October 1998, the second (734.1) in December 1998, and the third, (506.9) in April 1999. The highest number of counted insects (1991.1/plant) was observed during the autumn season, followed by winter (1467.9), spring (978.2) seasons and the least number (271.6/plant) was recorded in summer. On the contrary, the highest rate of infestation by the immature stages was recorded during the winter season, followed by spring, summer and autumn seasons (42.8, 29, 24.6 and 21.9%) of the total counted insects, respectively. The scale insect has been parasitized with the aphelinid species Encarsia citrina (Aphelinidae) with a maximum rate of 28.1 of the total count during August. The statistical analysis was performed for determining the relationship between the prevailing weather factors of daily mean temperature, daily relative humidity, wind speed and day-light in one hand and the population activity of F. fioriniae on R. hypoglossum plants on the other hand.

The bionomics of the scale insect Eriococcus araucariae (Muskell) (Homoptera: Eriococcidae) on Araucaria excelsa in Egypt.

The eriococcid species, Eriococcus araucariae (Muskell) is considered as an economic pest of Araucaria excelsa at Montazah garden, in Alexandria Governorate, Egypt. This study was carried out from June, 1998 till May, 1999. The obtained data revealed that the numbers of this insect were relatively low in autumn and winter months, then increased from the beginning of May to a total number/tree 72.0 +/- 1.60; continued its increase to reach 200.3 +/- 36.9/tree from the 2nd half of May and during June, July and August, with the highest number of inspected individuals (641.3 +/- 76.8/tree) in the 1st half of July. Thereafter, population began to decrease again from the beginning of September up to the end of April, decreased numbers 51.3 +/- 2.5/tree in the 1st half of September and (1.3 +/- 0.1/tree) in the 2nd half of October. Similarly, the occurrence of both immature stages and adults was also month-dependant all the year round. Adult males appeared three times in June, January and late March. There was a positive and significant relationship between the total population of E. araucariae and the daily mean temperature, wind speed and day light. This relation was negatively significant with the relative humidity.

Ecological studies on the snow scale insect, Lineaspis striata (Newstead) (Homoptera: Diaspididae) on Thuja orientalis in Egypt.

The snow scale insect, Lineaspis striata (Newstead) was recorded as an important insect pest of Thuja orientalis in Alexandria Governorate, Egypt. The present study revealed that the total individuals were in high numbers, (143.7 +/- 43; 141.8 +/- 20.7 and 149.0 +/- 48.5) during May, June and January, respectively. The fluctuating numbers of the immature stages have two peaks during June and November (6.9 +/- 0.7) and (20.5 +/- 5.0), respectively. The numbers of adult males reached the maximum (73.9 +/- 7.5) in October, while the females reached the maximum (88.7 +/- 2.2) in January. The insect has two annual generations. It is usually parasitized with Encarsia citrina (Aphelinidae), with maximum parasitization rate of 17.8 +/- 2.8 during August.