In another study it was concluded that rosiglitazone

In another study it was concluded that rosiglitazone induced apoptosis in K562 leukemia LY335979 in vitro, and that rosiglitazone-induced apoptosis in K562 leukemia cells was highly correlated with activation of caspase-3, decreasing telomerase activity, down-regulation of the anti-apoptotic protein Bcl-2, and up-regulation of the pro-apoptotic protein Bax ().
In our previous study, while atorvastatin and rosiglitazone did not affect the expression of CD38 and the level of bcl-2, these drugs significantly increased the level of Annexin V (chronic lymphocytic leukemia patients-CLL-) when compared with control group (<0.001). Both drugs significantly decreased the expressions of CD5 (=0.03) and ZAP-70 (<0.05) compared with control group. Atorvastatin and rosiglitazone increased apoptosis in lymphocytes of CLL in vitro ().
Introduction
Following tremendous advancement in pharmaceutical and medical research/technology, the use of biodegradable materials/polymers such as Poly (dl-Lactide-Co-Glycolide) (PLGA) nanoparticles/scaffolds/microparticles has become increasingly essential as a drug delivery system.
Examples include, inclusion of pharmaceutical excipient into polymeric matrices e.g. polymeric films, microsphere and nanospheres (Bibby et al., 2000), the use of nanoparticles containing therapeutic agents for site-targeted drug delivery and optimisation of drug treatment effects (Barzegar-Jalali et al., 2012, 2008; Hornig et al., 2009; Lee, 2004) and use of an electrospun Active Pharmaceutical Ingredient (API)-loaded resorbable Poly Lactide (PLA) fibre for local periodontitis treatment (Markus et al., 2012; Jandt and Sigusch, 2009; Balamurugan et al., 2008), etc.
PLGA has added advantages over other natural and synthetic polymers; it is biocompatible, it can be used to synthesise nano/micro-particles with tuneable physico-chemical properties and is an FDA (United States Food and Drug Administration) approved polymer (Imbuluzqueta et al., 2011; Ravi et al., 2008; Anderson and Shive, 1997.).
It not only increases the sustained release but also guards against enzymatic degradation of drugs. (Sabzevari et al., 2013; Tahara et al., 2011; Javadzadeh et al., 2010).
The relevance of the characterisation of the interaction between polymer and drug(s) cannot be over emphasised because of its denotations on formulation outcomes, product integrity, drug-release kinetics as well as probable polymorphic transitions. (Singh and Kim, 2007; Hsiue et al., 1998; Jansen et al., 1998; Katzhendler et al., 1998; Lorenzo-Lamosa et al., 1998; Puttipipatkhachorn et al., 2001; Wong et al., 2002; Takka, 2003).
This is particularly important in the pharmaceutical drug development process where a drug product with optimal characteristics must be identified in the early stages in order to prevent unwanted ‘surprises’ in the later stages of development or after the drug has been approved for usage. (Hilfiker, 2006; Preface, 2004).
The type of formulations used during the various stages of drug development also determines the final properties of the drug product: for example when suspensions are used, particle size must be controlled as this can affect bioavailability. (Pirttimäki et al., 1993; Jain and Banga, 2010).
The purpose of this study is to analyse the nature of the interaction (during microencapsulation) between three model drugs; metronidazole, paracetamol, sulphapyridine (shown in Fig. 1a–c respectively overleaf) and PLGA scaffolds using X-ray Powder Diffraction (XRPD).
XRPD was particularly chosen to monitor the encapsulation because of the superiority of the technique in differentiating between the structural properties of different materials. (Justin, 1999; Cullity, 1995; Karjalainen et al., 2005).
More so all three drugs used in the study have reported crystal structures (Ramukutty and Ramachandran, 2012; Burley et al., 2007; Gharaibeh and Al-Ard, 2011; Basak et al., 1848; Bar and Bernstein, 1985; Bernstein, 1988; Kirby et al., 2011) while the PLGA scaffold is amorphous thus making it easier to compare any changes that may arise in the X-ray patterns after encapsulation with already published data.

imatinib mesylate Interestingly this study showed that three

Interestingly, this study showed that three factors might have an effect on the knowledge scores of the respondents, which were, gender, years of clinical experience, and level of reluctance. The knowledge score was significantly higher among females when compared to males. This finding is similar to that reported by Reddy et al., which concluded that when mean knowledge scores were compared, females had higher mean scores as compared to males. The participants with more than 10years clinical experience had higher knowledge scores in comparison to the less experienced ones, but this difference was not of statistical significance. This finding can be explained by the notion that longer clinical experience increases the likelihood of participants being involved with medical emergencies; these previous experiences likely impact the retention of knowledge. However, Roshana et al. found that there was no association between the knowledge scores of the participants and the duration of their clinical work. Those who were not reluctant to perform CPR to a stranger had higher knowledge scores. This can be attributed to the fact that the readiness of health care providers to perform BLS is enhanced when their knowledge level is high. On the other hand, Roshana et al. found that most participants were not reluctant to perform CPR despite their lack of knowledge.
The most common justifications indicated by the participants for their lack of knowledge and skills were busy curriculum followed by no professional training available. Arsati et al. found that the lack of training and updates in an undergraduate program was the common cause for the lack of the knowledge. Almost all of our participants expressed the need for improved knowledge of BLS and agreed that it imatinib mesylate should be included in the undergraduate dental curriculum. Stafuzza et al. found that BLS training is fundamental to health care professionals.
Although uncommon, medical emergencies can occur in dental practice. Müller et al. found that medical emergencies are not rare in dental practice, although most are not life threatening. However, our results showed that the participants were not competent enough to deal with emergencies.
Gonzaga et al. found that theoretical information without practical training is not enough to assure CPR competence. Practical assessment is difficult to be performed through a questionnaire. Practical skills could not be assessed in the present study however; we focused on the cognitive levels of BLS. Other limitations of the study need to be acknowledged. The study was conducted at a single dental college. Therefore, generalizing the results is not plausible. Moreover, the inherent limitations present in the cross sectional and self-reported survey-based research should be considered. We recommend that future research address the assessment of practical skills required for BLS. Moreover, we recommend evaluating the BLS knowledge among other dental institutes and hospitals. This study would help in future development of training courses about BLS within the academic curricula and in adopting guidelines in cones regard in dental schools.

Conclusion

Funding/Support

Ethical approval

Conflict of interest

Other disclosures

Acknowledgements
We would like to thank the College of Dentistry Research Center and Deanship of Scientific Research at King Saud University, Saudi Arabia, for supporting this research project (Research project # IR 0113). The authors gratefully acknowledge Mr. Naser AlMuflehi for the guidance in statistical analysis. Our gratitude is also extended to all the respondents who participated in the present study.

Introduction
Cleft lip and palate is a developmental anomaly that has a significant genetic diversity. Inherited genetic mapping demonstrated distinct craniofacial morphologies like unilateral cleft lip palate, bilateral cleft lip palate, cleft of lip, cleft of alveolus or isolated cleft palate defects. Cleft lip and palate patients present with a number of complaints such as wide alveolar bone defects, congenitally missing teeth (hypodontia), supernumerary teeth, hypoplastic and impacted teeth. The treatment planning and clinical care of such patients are challenging and start at a very early stage of life. The ultimate goals of this treatment are to improve the functional capability and quality of life of these patients. The practical management is complex and may involve multidisciplinary approaches [such as dental, maxillofacial, orthodontics, prosthodontics, plastic surgery, speech therapy and psychological departments]. The orthodontists have an extensive role that starts on day one during infant orthopedic nasoalveolar molding and continues until comprehensive orthodontic treatment at adolescence. Orthodontic space closure is the treatment of choice with concomitant esthetic restorative contouring.

br Advantages of PAOO br Disadvantages of

Advantages of PAOO

Disadvantages of PAOO

Conclusion

Introduction
Since the beginning of last century, the problems of color in dentistry so eloquently described by Clark (1931) remains to be a challenge. Although tremendous advances have been made in the field, the reliance on subjectively assessing the shade of natural tooth, remains a commonly used practice today (Paravina, 2009; Brewer et al., 2004). The selection of an appropriate shade is normally made from a range of porcelain tabs supplied by the porcelain manufacturer in the form of a shade-guide (Smith and Wilson, 1998). Shades are selected according to closeness of match between tab and the natural teeth (Behle, 2001). Shade selection intrarater repeatability was found to be high using two different shade guide systems (Hammad, 2003).
It has been reported that the color difference between the fabricated shade and the intended shade could range between 2.50 and 3.84 ΔE units (Fazi et al., 2009). This finding can be a source of problems for the clinician since most likely the resultant restoration will not be clinically acceptable. Similarly, the selected shades and the obtained shades were spectrophotometrically measured using three different porcelain systems by Omar et al. (2008). The difference in the shades varied between 1.21 and 1.56 ΔE units.
The inadequacies of different shade guide systems have been reported previously in the literature (O’Brien et al., 1991). However, very few studies have examined the amount of variation in the color parameters of existing shade guides. One recent study by King and deRijk (2007) has closely examined the interchangeability of a commonly used shade guide. The results indicated that the differences observed between shade guides were larger than the variations induced by the experimental method used in their study. Therefore, they E64d concluded that the shade guides should not be considered interchangeable.
Therefore, the objective of this study was to attempt to provide baseline information regarding the consistency of the L∗a∗b∗ color parameters in a sample of a commonly used shade guide system using the ΔE color difference method.

Materials and methods
The L∗a∗b∗ color parameter of a randomly selected sample of 100 new VITAPAN Classical Vacuum shade guide (VITA Zahnfabrik, Bad Säckingen, Germany (were measured. The samples were obtained from the manufacturer’s local distributor and were given serial numbers from 1 to 100.
All color measurements were obtained by using a X-Rite ColorEye 7000A Spectrophotometer (X-Rite, Grand Rapids, Michigan, USA). This instrument is Alu family a bench top reference spectrophotometer which uses a dual beam pulsed xenon light source and is calibrated by NIST (National Institute of Standards and Technology) tiles. The spectral range is 360–750nm with a wavelength interval of 10nm. Reflectance measurements were made at 45° with illumination at 0°. The measurement aperture size used for the shade guide samples was Small Area View (SAV) which measures 0.75cm by 1.0cm. Fig. 1 shows a sample shade guide tab placed in the sample holder of the spectrophotometer (Fig. 1). The black colored trap latch of the sample holder acted as a backing for all the samples. All samples of the new shade guides were wiped with a clean lint-free cloth before placement for measurement. Since there were 100 shade guides, each consisting of sixteen tabs which were each measured five times to obtain an average for each tab; the total number of measurements was 8000 (100×16×5=8000).
The ΔE between the average L∗a∗b∗ value for each shade tab and the average of the 100 shade tabs of the same designation was calculated using the following formula:Statistical analysis was performed using the Student t-test to determine if there was any significance (α=0.05). All computations and statistical analysis were done using Excel software (Microsoft® Office Excel®, Redmond, Washington, USA).

Although majority of U A E

Although majority of U.A.E Blebbistatin uses bottled water for drinking (Maraqa and Ghoudi, 2015) but tap water still is being used in many households for cooking purposes and is thus added to food (Wait, 2008). The fluoride concentration of tap water from four different emirates in U.A.E was found to range between 0.04 and 0.3mg F/L. Tap water samples of Abu Dhabi and Dubai showed very low levels of fluoride, whereas tap water samples of Ajman had slightly higher fluoride levels. Varied fluoride level in tap water indicates that fluoridation of municipal water is not well regulated in U.A.E.
None of the bottled water samples tested contained recommended optimal fluoride level of 0.70mg F/L (USPHS, 2015) except locally produced Zulal brand (0.5ppm). Majority of bottled waters available in U.A.E were found to contain less than 0.1ppm of fluoride which is much lower in comparison with fluoride content of bottled water recorded in the previous studies conducted all over the world from 2000 to 2010 (Ahiropoulos, 2006; Aldrees and Al-Manea, 2010; Johnson and DeBiase, 2003; Thippeswamy et al., 2010). Decline in added concentration of fluoride in bottled water these days can be attributed to a change in the optimal fluoride recommendations, from 1mg F/L to 0.7mg F/L in order to reduce the risk of dental fluorosis as recommended by United States Public Health Service Reports and Recommendations (USPHS, 2015). The fluoride concentration in brand Volvic in our study was found to be 0.03mg F/L, which is lower than fluoride concentration ranging from 0.2 to 0.7mg F/L recorded for the same brand in previous studies (Aldrees and Al-Manea, 2010; Johnson and DeBiase, 2003). Another brand Arwa (produced locally in UAE) showed fluoride content of 0.04mg F/L which is much lower than 0.5mg F/L tested in a study where the water source was from Riyadh, Saudi Arabia (Aldrees and Al-Manea, 2010). Similarly, fluoride content of brand Evian found in our study was 0.1mg F/L, which was again lower than seen in other studies conducted in a last decade (Aldrees and Al-Manea, 2010; Cochrane et al., 2014; Johnson and DeBiase, 2003; Zohouri et al., 2003).
Around 65% of the bottled water brands tested had labeled their fluoride content however most of them were inaccurate (Table 3). Two brands, Jeema and Cool blue showed significantly lower fluoride levels of 0.04mg F/L and 0.09mg F/L respectively than their stated levels of 0.20mg F/L. On the contrary Alpin bottled water showed almost twice the fluoride content of 0.1mg F/L while the label stated 0.05mg F/L.
As per UAE law, there is no official regulation that requires bottle drinking water manufacturers to add fluoride; however, if it is added, it becomes mandatory to mention and inform consumers about fluoride levels on the label. Some of manufacturers of locally UAE produced bottled water don’t mention fluoride content on labels, thereby implies that these brands have no fluoride, although on testing with ISE method, all these non labeled brands had less than 0.1mg F/L. The present study also showed that there were very minor differences in fluoride content between different batches of same brand of bottled water. Seasonal variations such as hot weather and rainy seasons can account for these differences in fluoride content of the same brand (Grobler et al., 2001).
The fluoride content of fifteen popular beverages (fruit juices and carbonated drinks) available in U.A.E varied between 0.04 and 0.10mg F/L. These findings again are lower in comparison with values of 0.08–1.42mg F/L (Jiménez-Farfáni et al., 2004), 0.2–0.4mg F/L (Thippeswamy et al., 2010) and 0.06–0.15mg F/L (Quock and Chan, 2009) respectively. This difference in Blebbistatin fluoride levels can be attributed to the fact that different water sources containing different fluoride levels have been used by manufacturers of the beverages.

Conclusions
Fluoride levels in drinking water should be within the recommended and accepted levels to prevent dental caries and reduce the risk of dental fluorosis. The less than recommended fluoride level in drinking water (both tap+bottled) as well as beverages poses wider implications for an effective and comprehensive fluoride program for caries prevention in children. Oral health care professionals in UAE should always be aware of reduced levels of fluoride in drinking water (both tap+bottled) as well as beverages.

br Acknowledgments We are grateful to the

Acknowledgments
We are grateful to the anonymous reviewers for the suggestions. The partial financial support of the following programs is also greatly acknowledged. This work is supported by National Natural Science Foundations of China (Nos. 31301965, 31201817, 31272401, 91331118), National Statistical Scientific Research Project (No. 2013LY051), Anhui Provincial Natural Science Foundations (Nos. 1308085QC63, 1308085MA13), and the Program of Anhui Provincial Educational Commission Natural Science Foundation (Nos. KJ2012A216, KJ2013B198). This work is also supported by Fuyang Normal College Committee’s Educational Project (No. 2012JYXM71).

Introduction
There are approximately 1.7 million species identified by using morphological (i.e. Linnean) characters including 808 gymnosperm, and 90,000 monocots and about 200,000 dicots of angiosperm. This number may be a gross under-estimate of the true biological diversity of Earth (Blaxter, 2003; Wilson, 2003). Recently, overwhelming landmark publications (Table 1) on DNA barcoding (Hebert et al., 2003) (syn.: profiling, genotyping) based on highly conserved sequence informations provide new tools for systematics (Hebert and Barrett, 2005) and phylogeny (Wyman et al., 2004; Leebens-Mack et al., 2005; Jansen et al., 2006; Hansen et al., 2006). DNA barcodes consist of short sequences of DNA between 400 and 800 bromodomain inhibitor pairs that can be routinely amplified by PCR (polymerase chain reaction) and sequenced of the species studied.
Morphologically distinguishable taxa may not require barcoding; however, subspecies (ssp.), cultivars (cv.), eco- and morphotypes, mutants, species complex and clones can be diagnosed with molecular barcoding. Barcode of a specimen can be compared with sequences derived from other taxa, and in the case of dissimilarities species identity can be determined by molecular phylogenetic analyses based on MOTU, molecular operational taxonomic units (Floyd et al., 2002).
DNA barcoding was particularly useful for marine organisms (Shander and Willassen, 2005), including fishes (Mason, 2003; Ward et al., 2005); soil meiofauna (Blaxter et al., 2004) and freshwater meiobenthos (Markmann and Tautz, 2005); and extinct birds (Lambert et al., 2005). In the rainforests, rapid DNA-based entomological inventories were so effective (Monaghan et al., 2005; Smith et al., 2005) that tropical ecologists were the most active advocates of DNA barcoding (Janzen, 2004). More pragmatically, DNA barcodes have proved to be useful in biosecurity, e.g. for surveillance of disease vectors (Besansky et al., 2003) and invasive insects (Armstrong and Ball, 2005), as well as for law enforcement and primatology (Lorenz et al., 2005).
Barcoding has created some controversy in the taxonomy community (Mallet and Willmott, 2003; Lipscomb et al., 2003; Seberg et al., 2003; DeSalle et al., 2005; Lee, 2004; Ebach and Holdrege, 2005; Will et al., 2005). Traditional taxonomists use multiple morphological traits to delineate species. Today, such traits are increasingly being supplemented with DNA-based information. In contrast, the DNA barcoding identification system is based on what is in essence a single complex character (a portion of one gene, comprising ∼650bp from the first half of the mitochondrial cytochrome c oxidase subunit I gene sometimes called COXI or COI), and barcoding results are therefore seen as being unreliable and prone to errors in identification (Dasmahapatra and Mallet, 2006). Although the mitochondrial cytochrome oxidase subunit I (CO1) is a widely used barcode in a range of animal groups (Hebert et al., 2003), this locus is unsuitable for use in plants due to its low mutation rate (Kress et al., 2005; Cowen et al., 2006; Fazekas et al., 2008). In addition, complex evolutionary processes, such as hybridization and polyploidy, are common in plants, making species boundaries difficult to define (Rieseberg et al., 2006; Fazekas et al., 2009).
The number and identity of DNA sequences that should be used for barcoding is a matter of debate (Pennisi, 2007; Ledford, 2008). The main DNA barcoding bodies and resources are (1) Consortium for the Barcode of Life (CBOL) http://www.barcodeoflife.org established in 2004. CBOL promotes DNA barcoding through over 200 member organizations from 50 countries, operates out of the Smithsonian Institution’s National Museum of Natural History in Washington, (2) International Barcode of Life (iBOL) http://www.ibol.org launched in October 2010, iBOL represents a not-for-profit effort to involve both developing and developed countries in the global barcoding effort, establishing commitments and working groups in 25 countries. The Biodiversity Institute of Ontario is the project’s scientific hub and its director, (3) The Barcode of Life Datasystems (BOLD) http://www.boldsystems.org. The Barcode of Life Datasystems is an online workbench for DNA barcoders, combines a barcode repository, analytical tools, interface for submission of sequences to GenBank, a species identification tool and connectivity for external web developers and bioinformaticians. It is established in 2005 by the Biodiversity Institute of Ontario. The Consortium for the Barcode of Life (CBOL) Plant Working Group (2009) recommended rbcL+matK as a core two-locus combination. However, as these loci encode conserved functional traits it is not clear whether they provide sufficiently high species resolution. One of the challenges for plant barcoding is the ability to distinguish closely related or recently evolved species. Recently plant DNA barcoding has focused on several studies (e.g.Lágler et al., 2006; Chase et al., 2007; Kress and Erickson, 2008; Edwards et al., 2008; Newmaster et al., 2008; Newmaster and Ragupathy, 2009; Seberg and Petersen, 2009; Spooner, 2009; Starr et al., 2009; Zhang et al., 2009; Mansour et al., 2009a,b; Clerc-Blain et al., 2010; Kelly et al., 2010; Zuo et al., 2011; Dong et al., 2011; Du et al., 2011; Fu et al., 2011; Gu et al., 2011; Guo et al., 2011; Li et al., 2011a,b; Shi et al., 2011; Wang et al., 2011; Xiang et al., 2011; Xue and Li, 2011; Yan et al., 2011; Yu et al., 2011; Liu et al., 2012; Saarela et al., 2013; Techen et al., 2014).

To find the optimum effect of catechol dose response characteristics

To find the optimum effect of catechol, dose response characteristics of substrate for the enzyme PPO have been adopted in this study. Among the different concentration of catechol, 10mM concentration has been found to cause the higher response although the three different concentrations of catechol (10mM, 100mM and 200mM) produced the gradual increase in PPO activity for both the control and low temperature induced plants showing the validity of the substrate effect. Accordingly, the higher dose of catechol enhanced the PPO activity maximally in leaf extract therefore, higher colored quinones were synthesized which might be an effective approach for producing the essential pigments. Polyphenol oxidase catalyzes the oxidation of phenol to quinone which can covalently modify and crosslink various cellular nucleophiles, undergo melanin-forming auto oxidation reactions, or participate in other reactions. The Forskolin are found in higher plants and responsible for the enzymatic browning of raw fruits and vegetables. Such reactions are generally considered to be undesirable in food preservation and processing because of the unpleasant appearance and the concomitant development of a substandard flavor. Several lines of evidences revealed that PPO had been considered to be an important reagent for clinical diagnosis and micro-analytical immunoassays because of its high sensitivity (Siers, 1991) while many fruits and vegetables contain POD in amounts that contribute to browning-like reactions (Vamos-Vigyazo, 1981). Although PPO is involved primarily in the degradation of phenolics, they can also be degraded by POD (Thypyapong et al., 1995) and the activities of both enzymes have been found to increase in response to biotic and abiotic stresses (Kwak et al., 1996). Both PPO and POD have been considered in defensive mechanisms for plants against stress (Vamos-Vigyazo, 1981). Oxidative stress can arise from an imbalance between the generation and elimination of reactive oxygen species (ROS), leading to excess ROS levels that causes indiscriminate damage to virtually all biomolecules, leading, in turn, to various diseases and cell death (Scandalios, 2005). Reactive species can be eliminated by a number of enzymatic and non-enzymatic antioxidant defense mechanisms (Boullier et al., 2001) therefore, the higher activity of PPO and POD in response to low temperature in species of Pui vegetable might be linked to the defense mechanisms and the results are consistent with their findings.
Abiotic stress leads to a series of molecular, biochemical, physiological and morphological changes that adversely affect plant growth and productivity. Low temperature is a major factor limiting the productivity and geographical distribution of many species, including important agricultural crops. Higher plants manifest a unique capability of the synthesis of a large amount of diverse molecules so-called secondary metabolites, such as phenolic compounds and the synthesis and release of phenolics are induced by various biotic and abiotic factors (Makoi and Ndakidemi, 2007). It has been demonstrated in the previous study that these enzyme activities increased in response to different types of stress, both biotic and abiotic (Yadegari et al., 2007). More specifically, both enzymes have been related to the appearance of physiological injuries caused by thermal stress. During the experiment, it was observed that both low temperature induced and their respective controls caused the color pigmentation quickly, however low temperature induced leaves had higher pigmentation than the control, therefore, it is reasonable that cold acclimation causes the higher oxidation of phenolic compounds and might be an effective approach for producing the colored pigment essential for the several purposes. Of course, the phenomenon is a substantial mechanical and physiological way by which the plants survive in the adverse environment. The oxidation of phenolic compounds might be related to the temperature variation in the environment. It has been observed that the optimum PPO activity was found in the range of 25–30°C and then declined at temperature above 40°C (Doğan and Doğan, 2004).

Hijamah wet cupping is an effective treatment for

Hijamah (wet cupping), is an effective treatment for many diseases (Farhadi et al., 2009). Its efficacy to treat the non specific lower back pain has already been established (Farhadi et al., 2009). It was proven as a safe and better alternative therapy to the usual allopathic medical care (AlBedah et al., 2011; Ahmed et al., 2005). Some studies have found the effectiveness of wet cupping combined with drug treatment superior to the medical treatment alone (AlBedah et al., 2011). Beside this, wet cupping therapy has also got the immune-modulatory effects (Ahmed et al., 2005). Its ability to modulate the acetylcholine inhibitors has well been established. It was thus postulated that this aspect of Hijamah therapy can be used to treat other immune related diseases as well.

Case history
Mr. Muhammad H. (MH) is a 30year old male working and living in Australia. He works as Incident Management Analyst and also does the mechanical work on his car by himself as a hobby. Three years ago, when he was helping to unload a car engine from a truck, his right front leg scratched (a size less than 5 cent coin), however, he was not worried at-all at that time. After few weeks, he noticed that few bubble appeared on the affected leg, which burst out and left a mark with slight itching. He went to the doctor and was prescribed steroid cream. He started using the cream and the spots disappeared gradually. But this was not the end of story. Spots/lesions kept appearing and he kept using the cream, which not only cost him high but also resulted in skin thinning followed by easy bruising even with minimum shear. This made him really worried. Few days later, the lesions spread to the other leg, arm, back and the head (Fig. 1A–D). He visited the doctor and was again prescribed the high potency steroid combination cream namely Daivobet (Fig. 2A and B). This combination is used to treat psoriasis (Fig. 3A and B). The results were same as before i.e. as long as the cream was being used, the lesion would go away but as soon as the cream was stopped the problem would come back. He noticed that even during the regular use of cream, the incidence of appearing of the new lesion was unaffected, i.e. the steroid cream was not effective in preventing the new lesions. The situation was annoying and he finally was referred to the skin specialist for further review. The specialist ordered the biopsy of the lesion and kept him on steroid cream. The biopsy report came after few weeks and it failed to find any abnormality. This made him even more worried realizing that he is suffering from such a bad and progressive skin condition and doctors failed to establish any definite diagnosis. The plight was that according to doctors, there is no cure for the disease and the condition could only be managed rather slowed by the continuous use of steroid cream or other drugs. Moreover there is no option to avoid the side effects of medical therapy. Further, the cost of the cream was high i.e. 42.10 Australian dollars per four tube (Fig. 2A). Moreover this medicine is available through a complex prescribing procedure (Fig. 3A). Later on, the patient visited his home country and consulted a skin specialist, who confirmed the disease as psoriasis and advises him some other alternative drugs other than steroids. But the problem was same: no complete remission and non tolerable side effects. Finally he contacted the qualified Hijamah therapist and was given advice not to worry about it, as the Hijamah is an effective therapy for many diseases including psoriasis, by the will of Allah. A Hadiths says to the nearest meaning “indeed the best of treatments you have is Hijamah” (Bukhari, xxxx).

Methodology, results and discussion
Mr. MH was counseled and was given advice to seek help of ALLAH (the Creator) and the Hijamah therapy was started. At this point the severity of the disease was examined using the online tools like PASI (psoriasis area severity index) and it was found to be 2. The wet cupping sessions (using the sterile plastic cups to create a negative pressure on the skin and then performing the superficial skin incision to draw the stagnant blood) were designed to be performed once a week on the basis of diagnosis of the disease as psoriasis. He was advised to have minimum seven sessions to completely get rid of the disease. Hijamah was started and two days after the first session, lesions started to disappeared and reduced both in size and number. The patient continued for further two sessions and more than 90% of disease had gone. However, the patient could not continue further sessions despite his willingness due to his extreme business. It has been six months after the last session and all his lesions disappeared completely (Fig. 4A–D), and no itching is felt anywhere on the skin. The patient has not used any other type of therapy after that. Also no new lesion appeared anywhere except for some lesions at below his elbow after 6months (Fig 4E and F). One possible reason for appearance of new lesions could be the incomplete treatment as the patient received only three sessions instead of initially advised schedule of seven sessions.

Data from one randomized clinical trial have shown that

Data from one ceterizine randomized clinical trial have shown that increased levels of markers and mediators of inflammation such as C-reactive protein (CRP) and interleukin 6 (IL-6) are associated with future development of T2DM, suggesting the potential role of inflammatory markers in diabetogenesis (Pradhan et al., 2001). The possible connection between inflammation and T2DM is further strengthened by the finding that elevated levels of cytokines were observed in obese individuals, thereby causing hepatic insulin resistance in them. Tumor necrosis factor (TNF-α) is a cytokine which is produced by activated macrophages and it regulates the immune cells. More than a decade ago, it was discovered that TNF-α is overexpressed in the adipose tissues of obese mice, thereby establishing a clear link between obesity, T2DM and chronic inflammation (Hotamisligil et al., 1993; Diwan et al., 2012). TNF-α plays a pivotal role in systemic inflammation. In addition, TNF-α has been shown to increase the liver’s production of ceterizine and triglycerides but, at the same time, it causes insulin resistance through its effects on metabolism. TNF-α causes a significant decrease in the peripheral uptake of glucose in response to insulin, hence, playing a role in the insulin resistance in obesity and T2DM that often accompanies obesity (Priyadarshini et al., 2012). Elevated levels of pro-inflammatory cytokines such as TNF-α are known to cause insulin resistance in T2DM. Insulin receptor substrate (IRS) proteins are among the notable intracellular substrates used by insulin receptor tyrosine kinases in the insulin signaling pathway. Cell culture studies have shown that TNF-α causes interference in insulin signaling by inhibiting insulin receptor tyrosine kinase activity and tyrosine phosphorylation of one of its substrates, IRS-1 (Peraldi and Spiegelman, 1997). Similarly, findings from in vitro studies indicate that TNF-α could be exerting its anti-insulin effect by disrupting the insulin-stimulated tyrosine phosphorylation of insulin receptor and its substrates (Feinstein et al., 1993).
Oxidative stress is another underlying cause of inflammation in T2DM. Endothelial dysfunction is commonly observed in people with diabetes. This impairment in endothelium function is the common cause of diabetes-induced vascular disease. It has been hypothesized that hyperglycemia, activation of the advanced glycosylation end-product pathways and free fatty acid metabolites-induced activation of NFκB and NH2-terminal Jun kinases/stress-activated protein kinase stress pathways could be playing a central role in causing late diabetic complications such as insulin resistance and impaired insulin secretion in T2DM (Evans et al., 2002). Furthermore, oxidative stress has been shown to contribute to the fibrillization and aggregation of tissue specific as well as non-specific proteins both in T2DM and AD (Kamal et al., 2014). Hence, oxidative stress has been linked to inflammatory pathways in muscle cells and adipocytes and to impaired insulin secretion in pancreatic β-cells (Furukawa et al., 2004; Lin et al., 2005).
Another marker of inflammation is a high white blood cell (WBC) count. One study measured WBC in 352 nondiabetic Pima Indians aged 27±6years and they were followed-up for up to 5.5years. The findings of this study revealed that a high WBC count was an independent predictor of a worsening of insulin action and the development of T2DM among Pima Indians, suggesting the role of chronic low-grade inflammation in the pathogenesis of insulin resistance and T2DM (Vozarova et al., 2002). Elevated levels of other markers of inflammation, such as orosomucoid acid and sialic acid, are also associated with later development of T2DM. In one study of 12,330 men and women, aged 45–64years, who were followed up for a mean of 7years, different markers of acute inflammation were analyzed. Of those individuals, 1335 had a new diagnosis of T2DM. It was found in this study that elevated levels of sialic acid and orosomucoid acid were directly related to the development of T2DM in middle-aged adults (Schmidt et al., 1999). Hence, low-grade inflammation is a pathogenic determinant of T2DM and specific inflammatory processes have been recognized to play an important role in the pathology of diabetes, especially T2DM.

Another recent study concerning the conversion of metastatic papillary thyroid

Another recent study concerning the conversion of metastatic papillary thyroid carcinoma (PTC) into primary squamous cell carcinoma (SCC) has suggested that PTC can reoccur in the cervical lymph nodes, as reported in an 86-year-old woman 10years after total thyroidectomy (Lee et al., 2013). After thyroidectomy, the failure of radioiodine treatment may cause a recurrence of PTC and increased morbidity and caffeic acid phenethyl ester mortality. Hence, the more aggressive behaviour of the BRAF V600E mutation results in the need for a stronger treatment for PTC patients to overcome the recurrence of tumours (Xing et al., 2005). The independent role of the BRAF V600E mutation as a potential marker in the risk stratification of papillary thyroid cancer (PTC) patients can help to efficiently treat patients and prevent recurrent disease (Xing, 2007). Similar findings have also indicated a close relationship between PTCs carrying the V600E mutation and high expression levels of VEGF (vascular endothelial growth factor), which in turn is associated with aggressive tumour characteristics such as tumour size, extrathyroidal extension and tumour stage (Nikiforov, 2011). At the protein level, V600 in the glycine-rich loop of BRAF forms a hydrophobic interaction with P468, which stabilises the DFG motif by preventing the phosphoryl transfer to the DFG triad, finally locking it in an inactive conformation. As a result of the V600E variation, the substitution of valine with glutamic caffeic acid phenethyl ester disrupts that hydrophobic interaction and induces BRAF phosphorylation, which is associated with an up to 700-fold increase in the MEK–ERK signalling (Ziai and Hui, 2012).
Fine-needle aspiration (FNA) of biopsy material (thyroid nodules) is the most reliable way to preoperatively diagnose thyroid carcinomas carrying the BRAF V600E mutation. In the United States, approximately 60–70% of the biopsied thyroid nodules are characterised as benign, while 4–10% are categorised cytologically malignant (Adeniran et al., 2011). The nature of the remaining 20–30% of the nodules cannot be diagnosed due to cytological uncertainty. In such equivocal cytological contexts, testing FNA specimens for the BRAF V600E mutation has facilitated the definitive diagnosis of PTC (Adeniran et al., 2011; Rowe et al., 2006).
In paediatric PTC, appropriate surgery with adjuvant radioiodine ablation is often enough to cure the disease, even if the disease is quite extensive. This is because BRAF mutations are rarely found in paediatric PTC, or these mutations appear to cause the poor prognosis of PTC. Moreover, a high occurrence of the T1799A nucleotide mutation, which results in the V600E mutation (previously known as V599E), in the lymph node-metastasised PTC tumours, it may reflect the de novo development of thyroid cancer cells of increased malignancy. In another report concerning the lymph node metastasis of PTC, a novel mutation—the deletion of codon 601—appeared to be the cause of the genetic alteration underlying the progression of PTC cells in the lymph nodes (Vasko et al., 2005).

According to recent statistics released by the National Cancer Institute of the NIH (http://www.cancer.gov/cancertopics/types/melanoma), 76,100 new cases of melanoma have been reported in 2014. Massachusetts General Hospital documented a male approximately 68years old who developed metastatic melanoma to the groin and pelvis 11years after a melanoma on his right leg was excised (Sullivan et al., 2013). Additionally, in 2008, the highest (8420) estimated deaths in the United States were due to metastatic melanoma (Jemal et al., 2008). In the same year, Wajapeyee et al. (2008) used genomewide RNA interference screening to identify 17 factors—F-box protein (FBXO31)—necessary for oncogenic BRAF to regulate senescence in primary fibroblasts and melanocytes.
Dermatologists are typically on the forefront to identify patients with increased risk of melanoma due to genetic predisposition; however, mostmelanomacases are sporadic and result from moderate genetic risk factors (Udayakumar et al., 2010). The strongest genetic risks for melanoma development have been observed as aresult of genetic variations in the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene located on chromosome 9p21 (Nelson and Tsao, 2009). Studies have also identified a high frequency of BRAF somatic missense mutations in malignant melanoma. In addition, MC1R variants are strongly associated with BRAF mutations in non-CSD (chronic solar-damaged) melanoma (Fargnoli et al., 2008). Thus, high risk for melanoma is associated with the both the MC1R and BRAF genes. However, BRAF mutations have also been rarely detected in CSD melanomas (18.2%), as well as in acral (15.5%) and mucosal (12.5%) melanomas (Si et al., 1990).