br Conflicts of interest br Introduction

Conflicts of interest

Introduction
Esophageal benign lesions have been detected less often than malignant lesions, accounting for only 0.5% of autopsy cases, because most patients are asymptomatic [1]. However, benign esophageal lesions can be detected more often by the widespread use of endoscopes and an increasing awareness of the disease. Sebaceous glands are normally found in human hair follicles, but ectopic areas have been reported around the eyes and in the oral cavity, tongue, larynx, palms, soles, and external genitalia, which are lined with squamous cells. Sebaceous glands in the esophagus were first reported in 1962 by De La Pava and Pickren [2] and are rarely found. The apparent low incidence of this condition may be because of the lack of obvious clinical signs and symptoms. Most cases were discovered incidentally by endoscopy in patients referred for gastrointestinal tract examination.
Ectopic sebaceous glands (ESGs) are best distinguished from other yellowish plaques such as xanthoma through endoscopy. Esophageal xanthomas were first reported in 1984 by Remmele and Engelsing [3]. One study showed that the most common location of xanthoma was the stomach (76%), followed by the esophagus (12%) and sphingosine 1-phosphate receptor modulator (12%) [4]. Coincidently, both ESGs and xanthomas are detected in the lower esophagus and should be confirmed via tissue biopsy.

Case reports

Discussion
ESGs and xanthomas in the esophagus (Figure 5) have similar epidemiology, such as patient age (mean, 50 years), endoscopic features (yellowish, small, mildly elevated lesions), and clinical symptoms (asymptomatic), with good prognoses. To the best of our knowledge, no case reports have discussed their differences. We present three cases of ESGs and one case of xanthoma in the esophagus that had similar endoscopic findings and age distributions. A comparison between the esophageal ESGs and xanthoma is provided in Table 1.
ESGs and xanthomas are rarely found in the esophagus. For ESGs in the esophagus, the typical mean patient age at onset is 50 years, with almost equal distribution in men and women [5]. For esophageal xanthoma, also known as “xanthelasma” and “lipid island,” the mean patient age at onset is 54 years, with mild predominance in men [6,7]. ESGs are most likely the result of a metaplastic process rather than a congenital anomaly. As ESGs are derived from endodermal tissue, it is unlikely that they are derived from ectodermal tissue [8]. ESGs are rarely found in infants or children, supporting the belief that they are less likely to be a congenital anomaly [9]; rather, ESGs are suspected to be associated with reflux gastritis. Accordingly, the theory of an acquired metaplastic change of the esophageal epithelium was suggested in a 79-year-old man [10]. Only one of our patients had gastroesophageal reflux disease. All the patients were diagnosed with ESG in the lower esophagus. In our opinion, the theory of acquired metaplastic change is possible, but there is not enough evidence to support it.
The etiology of esophageal xanthomas is still unknown. One study reported a theory that gastric xanthoma is derived from focal mucosal damage in which the lipids were derived from broken-down cell membranes and captured by interstitial histiocytes [11]. This may explain why the esophageal mucosa has a better tolerance to damage than the gastric mucosa and the fewer reports of xanthoma in the esophagus [4]. No significant associated clinical symptoms or signs have been reported.
For ESGs in the esophagus, the number of occurrences has ranged from 1 to more than 100 (which was consistent with the findings in our patients), and lesion sizes have ranged from 1 mm to 20 mm, with the majority of cases being smaller than 0.5 cm [12]. Factors that affect the pattern and distribution of ESGs in the esophagus require further study. They have several different shapes and a yellowish appearance; smaller lesions are flat or dome shaped, or have a papular surface with irregular margins. Esophageal xanthomas are located most often in the lower esophagus and are about 2–10 mm in size [7]. They appear as well-defined, fern-like yellowish plaques scattered over the middle or lower esophagus, with the plaques being composed of clusters or groups.

To recover well from partial hepatectomy and to avoid postoperative

To recover well from partial hepatectomy and to avoid postoperative hepatic failure, morphological regeneration and functional restoration may be concerned. A previous study [6] reported that GamiSoyo-san (GSS) intravenous pharmacopuncture (intravenous injection of herbal extract) promoted the restoration of liver function, but not the regeneration of liver tissue after partial hepatectomy in rats.
On the basis of Korean medical theory, GSS is one of the formulas to treat Lesser Yang syndrome [7], including the diseases in half-exterior and half-interior [7], the diseases in the liver and gall bladder, and their meridians. These medicinal formulas are called harmonizing and releasing formulas [7].
From the previous study [6], we came up with an idea that these formulas may be applied to the patients who are going through a partial hepatectomy. Through a literature study on the classics of Korean medicinal prescriptions, two harmonizing and releasing formulas; SihoJigak-tang (SJT) and Danchisoyo-san (DSS) were selected for the present study.
Due to the low metabolic rate and the unconscious state of the patient, oral administration of herbal medicine is not appropriate after partial hepatectomy. Considering this problem, intravenous pharmacopuncture was applied in the present study, as it was in the previous study [6].

Materials and methods

Results

Discussion
Partial hepatectomy is required in the presence of primary or secondary liver tumors. It is generally considered that partial hepatectomy is warranted due to the large hepatic mass; however, it poses a high risk of fulminant hepatic failure [1]. Posthepatectomy liver failure is the leading cause of postpartial hepatectomy death (>60%) [4]. To prevent posthepatectomy liver failure, physicians are trying various methods [5].
Partial hepatectomy is known to have a bad influence on bile Torin1 cost and it increases serum TBIL. Bile leakage is a troublesome complication following hepatectomy [10] and exerts a harmful influence on liver regeneration [11]. Lederer et al [11] reported that small intra-abdominal bile leakage can suppress liver function and impair the regenerative capacity of the liver.
Liver regeneration is an orchestrated response induced by specific external stimuli, leading to sequential changes in gene expression, growth factor production, as well as morphological structure [12]. It is reported that complete functional restoration can be achieved within 12 weeks in humans, while liver volume remains at 73.2±14.8% of the preoperative level [13].
Based on Korean medical theory, the harmonizing and releasing formula treats Lesser Yang syndrome [7], and liver and gall bladder diseases. Therefore, from the viewpoint of Korean medicine, it is reasonable to hypothesize that the harmonizing and releasing formula may have a beneficial effect on the recovery from a partial hepatectomy.
The results showed that the intravenous pharmacopuncture with SJT significantly increased the liver regeneration rate (Fig. 1), and the intravenous pharmacopuncture with DSS significantly decreased the serum TBIL (Fig. 4).
In a previous study [6], intravenous pharmacopuncture with GSS promoted restoration of liver function, but not regeneration of liver tissue after partial hepatectomy in rats.
We compared the compositions of SJT and DSS used in the present study and GSS used in the previous study [6], and found that Paeonia suffruticosa Andrews and Gardenia jasminoides are the herbs contained in both DSS and GSS, but not in SJT.
Moutan Cortex is the sovereign medicinal [7] of GSS and is an important herb of DSS. The major actions of Moutan Cortex are invigorating the blood, dispelling blood stasis, and clearing the liver. Its nature is cold and its flavor is bitter and acrid. It enters the liver, heart, and kidney meridians, and is applied to clear the heat in the blood, activate the blood, and resolve blood stasis [14]. It also has anti-inflammatory and antihypertensive effects [15].

With regard to mouth opening amplitude we also obtained good

With regard to mouth-opening amplitude, we also obtained good results as shown in Table 1.
When comparing the results obtained in the research with the existent literature encompassing the symptoms of TMD and the diverse treatment modalities, such as the occlusal plate [2,22,23], traditional acupuncture [9–13,24], and use of analgesic and anti-inflammatory medications [2,25], the authors were very encouraged by the effectiveness of the proposed treatment.

Conclusion

Introduction
CD4+CD25+Foxp3+ regulatory T (Treg) comt inhibitors are vital for preserving self-tolerance [1,2] and play critical roles to control immune system homeostasis [2]. Growing documents indicate that Treg cells are able to inhibit the function of Th1, Th2, Th17, and other effector cells, inhibit inflammation, and prevent autoimmunity [3,4]. Therefore, the lack or dysfunction of Treg cells often leads to autoimmune diseases, such as systemic lupus erythematosus [5], type I diabetes, and inflammatory bowel disease [2,6]. As a result, it seems that conditions in which Treg cells are being promoted may consequently alleviate the severity of autoimmune diseases.
Since ancient times, people have looked for cures for illness in nature. The use of natural medicines has intensified in recent times because of the low level of side effects, cost, and efficacy against several human illnesses [7]. Berberine (2,3-methylenedioxy-9,10-dimethoxyproto-berberine chloride; BER) is an isoquinoline alkaloid with a broad spectrum of pharmacologic and biochemical effects and is the main active component in plants, such as Berberis spp. and goldenseal [8]. In traditional medicine, BER has been repeatedly applied as an anticancer, antihypertension, antidiarrhea, antiarrhythmia, and antibiotic agent. Moreover, there are several studies suggesting the possibility of its application for the treatment of autoimmune diseases. For instance, BER has been reported to play a role in the management of immune inflammatory diseases, such as experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis) [9–11], type 1 diabetes [12], rheumatoid arthritis [13,14], experimental autoimmune tubulointerstitial nephritis [15], and colitis [16]. In these studies, BER has been reported to affect by activating dendritic cell apoptosis, inhibiting Th1 and Th17 differentiation, decreasing the permeability of blood–brain/intestinal epithelial barriers, and downregulating inflammatory cytokines and antibodies. However, little is known about the role of natural compounds in controlling the differentiation and functions of Treg cells. Because Treg cells regulate the functions of effector T cells, we hypothesized that some therapeutic herbs may suppress inflammation by promoting Treg cell differentiation, thus inhibiting inflammation and preventing autoimmunity. Therefore, in this study, we aimed to evaluate the subacute effects of BER on CD4+CD25+Foxp3+ Treg cells of the BALB/c mice spleen.

Materials and methods

Results
Of all the treatments, only spleen cellularity decreased significantly (p<0.05) in cyclophosphamide-treated mice compared with that in vehicle-treated mice. The absolute (total) number of spleen tissue CD4+CD25+FoxP3+ Treg cells associated with 10 mg/kg BER group was significantly decreased compared with the corresponding values in tissues recovered from vehicle control mice (Table 1). Using the total numbers of CD4+ cells in each treatment group\'s cell population analyzed as a 100% baseline, the relative percentages of spleen CD4+CD25+FoxP3+ Treg cells in samples from the mice treated with 10 mg BER/kg and with 20 mg cyclophosphamide/kg were also significantly lower than those in tumors from the vehicle control mice. However, BER at the dose of 5 mg/kg did not cause any significant change in these percentages. On the other hand, the absolute number of spleen CD4+ T cells and their relative percentages based on whole splenocyte levels in the sample set as a 100% value (from both 5 mg and10 mg BER/kg-treated mice) did not show any significant changes compared with the values from vehicle control group.

Erythrina genus has been extensively examined in

Erythrina genus has been extensively examined in terms of its taxonomy and chemical composition. However, very little information is available concerning biotechnological attempts for natural products production within that genus. Garcia-Mateos et al., showed that an unexpected profile of oxygenated alkaloids was observed in undifferentiated callus of Erythrina Coralloides and Erythrina americana[12]. Furthermore, San Miguel-Chavez et al., showed that jasmonic SCR 7 elicited E. americana cell culture has led to reduction in alkaloid accumulation [13]. Among the most common and effective elicitors used for stimulating secondary metabolites production in plant cell culture are the carbohydrate fractions of fungal and plant cell walls, MeJA, chitosan and/or heavy metal salts. In particular, jasmonates have been long regarded as transducers of elicitor signals for the production of plant secondary metabolites. Application of elicitors results in the induction of signaling compounds, including jasmonic acid and or MeJA, as well as the downstream up regulation of secondary metabolites. In contrast to salicylic acid being an elicitor of limited secondary metabolite classes, jasmonates seem to be general natural products inducer via the activation and de novo biosynthesis of transcription factors that up regulate genes involved in secondary metabolites production [14]. For example, jasmonates induce the accumulation of terpenoids, flavonoids, alkaloids and phenylpropanoids [15]. The aim of this work was to examine MeJA elicitation effect on cell suspension culture of Erythrina lysistemon regarding the accumulation of alkaloids, flavonoids, pterocarpans and phenolic acids using an MS-based metabolomic approach.

Material and methods

Results and discussion

Conclusions
This study provides the first report on E. lysistemon cell suspension culture metabolite fingerprint via UPLC-MS. A metabolomic approach was used to investigate secondary metabolites viz. alkaloids, flavonoids and triterpenes and their reprogramming in response to MeJA elicitation. The results confirm MeJA elicitation effect on terpenoid accumulation and extend our knowledge base concerning secondary metabolism in other legume species [27]. Comparative metabolic profiling of E. lysistemon cell suspension culture and in response to elicitation using MeJA, revealed an activation in sterol/triterpenes formation, see model depicted in Fig. 4. The effect of other elicitors on secondary metabolites accumulation in Erythrina cell culture could also provide more holistic insight into elicitation effect within that genus and how it can reprogram its different secondary metabolite pathways.

Conflict of Interest
The authors declare that they have no conflict of interest.

Compliance with Ethics Requirements
This article does not contain any studies with human or animal subjects.

Acknowledgments
Dr. Mohamed A. Farag acknowledges the funding received by Science and Technology Development Fund STDF, Egypt (grant number 12594), and the support of the Alexander von Humboldt Foundation, Germany. We also thank Dr. Christoph Böttcher, Leibniz Institute of Plant Biochemistry, Germany, for assistance with the UPLC-MS. We are grateful to Dr. Tilo Lübcken, University of Dresden, Germany, for providing R scripts for UPLC-MS data analysis.

Introduction
Timolol maleate is a β-adrenergic blocking agent that exhibits an anti-hypertensive activity, protects against angina pectoris, and myocardial infarction. Due to its short elimination half-life (4h), it is orally administered twice daily. Additionally; because of poor bioavailability (50%), a high oral dose of 10–60mg/day was required. As an adverse effect, bronchospasm was reported in some patients [1].
Transdermal delivery represents an attractive solution to oral problems. It bypasses the liver first pass effect; hence the bioavailability is expected to be increased. Additionally, it can SCR 7 be simply terminated and removed from the skin, if any of the side effects show up. Furthermore, the use of the vesicular system in the transdermal drug delivery may sustain the release of the drug, thus lowers its frequency of administration [2]. Despite the many advantages of the skin as a site of drug delivery, only few drugs are currently available in the market as transdermal delivery systems. This is because the inherent limitation of transdermal drug absorption, which is imposed by the outermost layer of the skin, the stratum corneum (SC) [3]. From 1991, several researches were focused on transfersomes in transdermal drug delivery system to overcome this intrinsic barrier. Transfersomes can penetrate efficiently various transport barriers, even through the pores or constrictions that would be confining for other particulates of comparable size. This capability is due to the self-adaptable and extremely high deformability of the transfersomes’ membrane [4]. In contrast to other methods permeating the skin; transfersomes create drug depots in the skin that can slowly and gradually deliver the material under the skin and/or the systemic circulation without invasion [5]. Transfersomes are complex aggregate, composed of phospholipids, surfactant, and water; prepared by thin film hydration or modified hand shaking, lipid film hydration technique [5].

Currently renal histological changes are identified according the

Currently, renal histological changes are identified according the International Society of Nephrology (ISN)/Renal Pathology Society (RPS) Classification of LN [7] which is entirely based on glomerular changes. It was designed to eliminate ambiguities and standardise definitions. Major changes from 1995 modified WHO classification [8] include better standardisation of renal biopsies in lupus patients [7] and separation of segmental and global lesions [9] which was suggested by a study in 2000 [10] who concluded that cases with diffuse proliferative LN and segmental lesions have poorer prognosis than those with global diffuse proliferative.

Materials and methods
The study group comprised a total of 148 biopsies diagnosed as lupus nephritis from two large tertiary medical centres in Jeddah (Western region of Saudi Arabia); King Abdulaziz University Hospital (period from 1995 to 2011) and King Faisal Specialist Hospital and Research Centre (2000–2011). Patients’ histological materials were retrieved from the archive of department of Pathology in the above mentioned centres. The microscopic criteria described in LN, and the definition of terms, were collected from the literature. The renal biopsy specimens were studied by light microscopy, immunofluorescence, and Sennoside A microscopy. Haematoxylin and Eosin (H&E), Periodic Acid-Schiff (PAS), Masson Trichrome and Jones Methenamine Sliver (JMS) stained slides of cases were re-examined to retrieve data according the standards of defining diagnostic terms reported elsewhere [11].
The activity and chronicity indices (AI and CI) were retrieved if were reported whenever possible and re-reported for cases that were not reported using the semi-quantitative scoring schema developed by Austin et al. [12]. Each activity and chronicity factor is graded on a scale of 0, 1, 2, and 3 depending on the percentage of involvement of all viable glomeruli (AI) and on all glomeruli (CI) present in sections; where 0 (absence of lesions), 1 (lesions involving up to 25%), 2 (lesions involving 25–50%), and 3 (lesions involving >50%). The activity items cellular crescents and necrosis are weighed by a factor of x2.
Results of immunofluorescence for immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), C3, C4, C1q and fibrinogen deposits were semi-quantitatively graded from 0 to 4 according to the intensity of fluorescence. The immunofluorescence findings of each patient were collected and analysed. Electron microscopy reports were used whenever needed for subendothelial, subepithelial, mesangial and intramembranous electron dense deposits. Renal involvement was assessed and cases were reclassified using both the modified WHO and ISN/RPS classifications wherever were not used . For categorisation of classes III and IV of ISN/RPS classification, active lesions were considered according to the presence of cellular crescents, fibrinoid necrosis, and a chronic lesion when glomerular sclerosis, and interstitial fibrosis are present [7].
Patients’ clinical data were collected from the medical archives of departments of Internal medicine. The clinical findings were analysed as patients’ age, sex, nationality, the presence of hypertension, diabetes, renal dialysis before and after renal biopsy, renal impairment before renal biopsy, and nephrotic syndrome. Laboratory results were also analysed including; haemoglobin, erythrocyte sedimentation rate ESR, serum C3, C4, anti-nuclear antibodies (ANA), anti-DNA, CRP, anti-cardiolipin IgM, anti-cardiolipin IgG, urine protein, urine RBC, Urine cast, and 24h protein were also retrieved. Revision of therapies applied were also collected; hydroxychloroquine (Plaquenil®) azathioprine, cyclophosphamide, pulse steroid prednisone, mycophenolate mofetil (CellCept®), methotrexate, cyclosporine. Patient mortality records were collected.
The work in this study was in accordance with the ethics committee of Faculty of Medicine, King Abdulaziz University, Saudi Arabia, and according to the ethical guidelines of the 1975 Declaration of Helsinki. Statistical analysis was done in the Statistical Package for Social Sciences (SPSS®) version 16. Frequencies and results were presented as median (range).

Importantly in a recent country wide survey in Ghana

Importantly, in a recent country-wide survey in Ghana, Benbow et al. (2013) often found presence of M. ulcerans in water bodies in BU-endemic regions, but not in non-endemic regions. Garchitorena et al. (2014) explored the spatial and temporal variation of M. ulcerans in a variety of aquatic ecosystems. They found that while low oxygen, high temperature swamps were a preferred location for M. ulcerans, colonization dynamics in aquatic systems varied throughout the year and were correlated to rainfall. Their results indicate that the environment may be more favorable to the bacteria at certain times of year and that transmission is a complex interplay between the biota and the INCB 018424 cost of the system. Merritt et al. (2005) proposed that “poor water quality influences biological communities, leading to increased growth and proliferation of M. ulcerans in aquatic habitats.” A study of mycobacteria in brook waters, conducted by Iivanainen et al. (1993), found that culturable counts of slow-growing mycobacteria were most negatively correlated to pH. Likewise, counts were most positively correlated to chemical oxygen demand and metals concentrations. One might expect M. ulcerans, a slow-growing mycobacterium, to thrive in similar environments to those bacteria studied by Iivanainen et al. (1993). Previous work has shown that the optimal pH growth range of M. ulcerans varies between 5.4 and 7.4 (Portaels and Pattyn, 1982), and that unlike many other mycobacteria, M. ulcerans has a preference for low oxygen conditions (Palomino et al., 1998; Garchitorena et al., 2014).
The assumption that M. ulcerans exists in environments with poor water quality is supported by many studies of BU incidence relative to land use and known chemical trends associated with these land uses (e.g., increased nitrogen in agricultural areas), and more recently, by work exploring the relationship between the distribution of M. ulcerans and the condition and use of the landscape upgradient from the sampling site (Carolan et al., 2014b). Areas with high nitrogen and phosphorus concentrations will likely be a preferred environment for the growth of M. ulcerans, as environmental nutrient enrichment has been linked to the emergence of other direct-transmission and vector-borne bacterial diseases (Johnson et al., 2010). Duker et al. (2004) suggested a connection between arsenic enrichment in soil and water and incidence of BU. The positive correlation of mycobacterial population with metals concentrations suggests that BU incidence may be higher near mining sites, as heavy metals are commonly associated with tailing waste from mining activity (e.g., Walker et al., 2006). Taken together, previous studies about M. ulcerans suggest that some difference in environmental conditions, human interaction with the environment, or both, INCB 018424 cost must exist between endemic and non-endemic communities to explain the difference in BU morbidity.
In this work, we explore the relations between water quality and the incidence of BU in Ghana, where more than 1000 cases of BU were reported in Ghana alone in 2010 (WHO, 2011).
This study seeks to answer the following questions: (1) Is there a difference in water quality between endemic and non-endemic communities? (2) Is there a difference in water quality between types of water bodies within these communities? and (3) If there are differences, do they relate to the postulated environment for M. ulcerans (high metal concentrations, low pH, high nutrient concentrations)? This study focuses on mining regions and particularly on “galamsey” (gather-and-sell), or artisanal small-scale, gold mining areas. These areas are characterized by significant localized disturbance, most notably pools of water associated with active or defunct ore-washing stations. Galamsey operations, which are poorly regulated and often unregistered and/or illegal, have no obligation to remediate spent mining areas, leading to long-term environmental degradation. Multivariate statistical methods are used to describe variation in water chemistry, water-body type, and surrounding land use. No pathogenic data are presented here and we did not directly sample for the presence of M. ulcerans. Rather, this work serves as a first step to explore links between Buruli ulcer incidence and the well-documented environmental niche of the bacteria. More broadly, this research works toward identifying water bodies hazardous to human health in at-risk communities.

At the seasonal scale our C reached minimum in the

At the seasonal scale, our C reached minimum in the hot dry summer and maximum in spring. This differs slightly from several studies in very different climates: Riou (1975) and Fu et al. (2004) showed that in equatorial and temperate climates, C reached maximum in the cold wet season and minimum in the hot dry season. Monthly values of C obtained by McJannet et al. (2013b) ranged from 0.67 to 1.17 and the minimum was reached in the coolest month (July) in a tropical sub-humid climate.
Seasonal heat storage does not appear to be the main factor involved in our study since variation in the monthly amount of heat storage (G) was in the same order of magnitude in the reservoir and in the pan and both BREB and Penman results showed the same trend. Advection effects, which are particularly significant in arid environments, could be responsible for this seasonal variation (Oroud, 1998). The difference between advection effects on the reservoir and on the pan is hard to quantify, but can vary considerably depending on the properties of the direct environment.

Conclusion
In this part of Central Tunisia where annual precipitation is about 300mm, annual csf1r has varied by more than 25% over the last 20 years. Four different approaches and three years calculation gave results ranging from 1400 to 1900mm. The agreement between physical and isotopic methods led to an estimation of the annual evaporation of 1700mm for the period 1989–2011. The annual Colorado pan conversion coefficient was 0.8 and varied from 1.0 in spring to 0.76 for the rest of the year.
Rarely considered, the scarcity and the representativeness of data for estimating evaporation were tested. An error of 10% in relative humidity can lead to 40% uncertainty in evaporation values calculated with the Dalton equation. Removing 40% of the daily input data led to an additional uncertainty of about 20% using the Dalton and BREB equations. We finally estimated the overall uncertainty in evaporation values around 15%. The Penman approach appears the most robust. It gave an annual evaporation rate of 1600mm for the period 2003–2006.

Conflicts of interest

Acknowledgements
This research was supported by the European project Wassermed (“Water Availability and Security in Southern EuRope and the Mediterranean,” European Commission FP7 n°244255), by the French projects ANR-CEPS Groundwater Arena and ANR-TRANSMED Amethyst (“Analyzing the vulnerability and adaptive capacity of North Africa\’s agricultural groundwater economy” and “Assessment of changes in MEdiTerranean HYdroresources in the South: river basin Trajectories,”, respectively), and by the MISTRALS/SICMED project Dyshyme (“Dynamiques socio-hydrologiques en Méditerranée”).

Introduction
Climate change is predicted to lead to an intensification of the global hydrological cycle (Huntington, 2006). Freshwater resources in dry subtropical regions may be impacted adversely, but favorably affected at higher latitudes (Cisneros et al., 2014). Quantifying current and future freshwater availability is a critical aspect of adapting to changing and variable climate because access to sufficient freshwater is linked to food security, human health, ecosystem health, land use change, economic development, and regional conflicts (Schuol et al., 2008).
The Brahmaputra River basin located in south Asia is one of the world\’s major river basins for human and ecological needs and supports the livelihoods of over 66 million people through subsistence agriculture. Despite the growing attention to quantify freshwater resources and to assess the vulnerability of freshwater to global change (Alcamo and Henrichs, 2002; Faramarzi et al., 2009; Lehner et al., 2006; Oki and csf1r Kanae, 2006; Piao et al., 2010; Schuol et al., 2008; Srinivasan et al., 1998a,b; Vörösmarty et al., 2000), basinwide assessments of the impacts of climate and land use change on freshwater availability in the Brahmaputra basin remains quite limited.

The different studied aquifers Fig are described below

The different studied aquifers (Fig. 2) are described below in chronological order. The Brussels Formation is an early Middle Eocene shallow marine sand deposit in central Belgium. The Brussels Sands occur in a 5-Iodotubercidin Supplier 40km wide SSW-NNE oriented zone in central Belgium. These sands fill an approximately 120km long and 40km wide embayment which ended in the north of the Province of Antwerp in the North Sea. The 5-Iodotubercidin Supplier of the sands is characterized by two central major SSW-NNE trending troughs and several minor troughs with the same orientation. The Brussels Sands consist of unconsolidated quartz sands with variable percentages of feldspar, flint, glauconite, lime and heavy minerals (Gulinck and Hacquaert, 1954). The groundwater in the aquifer is of CaHCO3 type because of the presence of lime in the Brussels Sands and the layers above. At several locations the most shallow part of the aquifer has increased concentrations of nitrate, chloride and sulfate correlated with antropogenic activity (Peeters, 2014). The Berchem Formation is an early Miocene shallow marine sand deposit in the north of Belgium. The Berchem Formation consists of green to black, fine to medium grained, often slightly clayey, very glauconiferous sand. The sand is rich in shells which appear dispersed in the sediment or concentrated in subhorizontal layers. At some locations however, the sand can be decalcified. The Diest Formation is deposited in the late Miocene during a large transgression. In erosive trenches, the deposit can be more than 100m thick. The Diest Formation consists of gray-green to brownish glauconiferous coarse sands wherein sandstone layers often occur. The unit contains almost no fossils, except very local. The Kattendijk Formation is deposited in the early Pliocene. The Kattendijk Sands consist of dark gray to green-gray, fine to medium grained, slightly clayey glauconitic sand. Shells appear dispersed in the sand but also concentrated in one or more layers. The late Pliocene Mol Formation is a white coarse to medium grained sand deposit. It sometimes contains lignite and clay lenses. Locally the lower part is slightly glauconiferous (Laga et al., 2001). Both the Brasschaat and Merksplas Formation are late Pliocene estuarine deposits occurring in the northern Campine area. The Merksplas Formation consists of a gray medium to coarse grained sand with glauconite and wood fragments. The sands contain shell fragments in the lower part and occasionally gravel. The Brasschaat Formation is a dominantly sandy complex with a grain size distribution ranging from very fine to medium grained sand. Beside typical minerals such as micas and glauconite, the unit also contains vegetation remains, peat and wood fragments. The Merksplas and Brasschaat Formations are partly lateral facies (Gullentops et al., 2001). The Formations of Berchem, Diest, Kattendijk, Mol, Merksplas and Brasschaat together form the Neogene Aquifer. The natural groundwater compostion of this aquifer is characterized by low levels of chloride (<25mg/l). The composition of the groundwater is further determined by the oxidation of organic matter creating a strong vertical variation in groundwater quality. Pyrite oxidation occurs in the shallow groundwater introducing high amounts of sulfate (to 100mg/l) and iron (>50mg/l). Deeper in the aquifer these concentrations decrease due to sulfate reduction (Coetsiers et al., 2014).

Results and discussion
Fig. 3 shows a chart summarizing the data of the ATES systems and the ambient values compared with the Flemish drinking water standard. The chart shows upward or downward trends for some of the considered species for several of the investigated ATES systems. The measured values however stay well within the drinking water standard for calcium, sodium, magnesium, sulfate and chloride. For the pH, manganese, iron and ammonium the analyses for several ATES systems show values outside the drinking water standard. This is especially the case for iron and ammonium where for all ATES systems, except respectively one (C) and two systems (C and E), values above the drinking water standard are reported. However, for most of these cases the ambient values measured in the VMM monitoring network are also outside the drinking water standard, and thus likely caused by the aquifer characteristics (e.g. mineralogy, organic matter content).

br Experimental The hot compression tests were carried out on

Experimental
The hot bradykinin receptor tests were carried out on Gleeble-1500 to obtain the flow curves over four temperatures (300, 350, 400, and 450 °C) with three strain rates (0.01, 0.1 and 1 s−1). The alloy, used in the present study, was as extruded Mg–8Al–1.5Ca–0.2Sr with the nominal composition of 8 wt% Al, 1.5 wt% Ca, 0.3 wt% Mn and 0.2 wt% Sr. Cylindrical specimens with a diameter of 10 mm and a height of 15 mm were machined with the compression axis parallel to the extruded solid bar axis. To observe the microstructure, cross-sections parallel to compression axis were cut from the deformed specimens. The samples were mounted, polished and etched. Then, the microstructure was observed by optical microcopy with an image analyzer.

Mathematical modeling

Results and discussion
The flow stress curves obtained at various temperatures and strain rates are presented in Fig. 1. All the curves display the normal single peak and concave-down appearance associated with DRX. The flow stress increases to a maximum and then decrease to finally attain a steady state in the usual way. Most of the curves at strains from −0.02 to −0.15 are camber line, except the flow curves at 300 °C and strain rates of 0.1 s−1 and 1 s−1. The flow curves of these two conditions at strains from −0.02 to −0.15 are close to a straight line, indicating that twinning occurs during deformation. This can be proved by Fig. 2.
Optical microstructure at various strain rates and a temperature of 300 °C with a strain of −0.6 are displayed in Fig. 2. Twins are observed inside grains and the number of twins increases with strain rate. It is well known that in order for a polycrystal to accommodate deformation, five independent slip system have to be activated. Basal slip and prismatic slip can only provide two independent slip modes. 1st order pyramidal slip can offer four independent slip modes, but this can not accommodate uniform deformation. Only 2-order pyramidal slip, with its non-basal Burger vectors, will accommodate deformation along the c-axis and meet the requirement for five independent slip modes. But dislocation slip can not meet requirement of uniform plasticity for its low migration velocity at high strain rate and so caused the initiation of twinning. Twinning was not considered during simulation. Therefore, flow stresses, microstructure evolution and volume fraction recrystallized under these conditions were not simulated.
In order to obtain the saturate flow stress and the rate of dynamic recovery, derivate method was applied to the flow stress curves of Fig. 1. The work hardening rates (dσ/dε) under various temperatures and strain rates are displayed in Fig. 3. It can be seen that the work hardening increases with increasing temperature. According to the work hardening rate curves, the critical strain εc, the peak strain εp and the saturate stress σsat can be determined [24,25]. The rate of dynamic recovery r can be calculated by the slope of work hardening rate [15]. Then, the derived work hardening curves can be obtained using Eq. (8).
The derived work hardening curves under different deformation conditions are displayed in Fig. 4. It can be seen that the derived work hardening is higher than the flow stress from critical stress. The work hardening approached rapidly to the saturate flow stress before a strain of −0.2, due to high work hardening rate. It can be concluded from Fig. 4 that the work hardening increases with decreasing temperature and increasing strain rate.
The comparison between the simulated flow curves and the experimental flow curves are illustrated in Fig. 5. Both the simulated flow curves and the experimental flow curves attain a peak, followed by continuous flow softening. At 350 °C with a strain rate of 0.1 s−1, the simulated flow stress is a little bit higher than experimental flow stress after the critical strain, and then lower than the real flow stress. This discrepancy may be attributed to the possible involvement of additive high energy sits for nucleation, such as dislocation tangle and dislocation pinning, and the effect of creep behavior on grain boundary migration which has not been taken into account during simulation. Nevertheless, the simulations agree well with the experimental results.

FGM has many health effects including recurrenturinaryand vaginal infections

FGM has many health effects including recurrenturinaryand vaginal infections, chronic pain, infertility,hemorrhaging,epidermoid cysts, and difficult labor. It has also its psychological impact and abnormalities in the female sexual function.
Throughout Egypt, many studies have been conducted to determine the pattern and prevalence of FGM, but those studied the risks of FGM and its effect on women’s sexual life are scare. Therefore, this Cyanine3.5 carboxylic acid study was carried out.

Objective

Discussion
In Egypt, 91% of women aged 15–49years have been circumcised despite banning of this practice by the government.
Rural women are more likely to be circumcised than urban one. This was concomitant with the results of the present work, where 57.7% of cases were of rural origin.
Egyptian demographic health survey 2008 (EDHS) illustrated that the possibility of FGM also declined with educational level and was higher among women in lower social strata. This was also proved by the current work (39.3% of cases got university education and more versus 43.3% of their control group and 44.9% with perceived low social class versus 33.8% of their control group).
EDHS 2008 stated that all circumcised women had this act before the age of 15years. The tradition is that all girls are circumcised before puberty. The same was proved by this study, where the mean age of FGM was 9.7±2.12years. Nearly half (48.9%) of FGM was carried out by dayas or midwives, which was nearly similar to the results of EDHS 2008.
FGM has many frequent health impacts. They include infection (mainly urinary or vaginal), pain, infertility, hemorrhage and complications during childbirth. That was concomitant with the results of the present work, where 87.9% of cases experienced complications. Cases were at risk of obstructed labor (OR=1.745) and postpartum hemorrhage (OR=2.855). Three-quarters of cases (74.6%) had assisted delivery (OR=7.728).
Cases were at risk of dysmenorrheal (OR=3.750). FGM may end in fibrosis which could predispose to dysmenorrheal.
The present work revealed a significant association between FGM and female sexual function, where reduction of all aspects was obtained (namely desire, arousal, lubrication, orgasm, satisfaction and pain). The total score of female sexual function for cases was significantly lower than their control (14.3±5.93 for cases versus 25.9±3.44 for control).
Women with FGM have more sexual adverse effects. One study that was conducted in Ismailia, Egypt, proved that women with FGM have higher rates of dyspareunia and lack of sexual desire. This could be explained by the fibrosis and rigid scar tissue following FGM which predisposes to narrowing of the vaginal orifice and muscular spasm which makes intercourse painful and difficult. These physical factors will predispose to psychological one, where the painful experience will drive women to lose both sexual desire and satisfaction.
Despite all previously proved side effects of FGM, the present work revealed that 52.6% of cases convinced with this practice. Moreover, 46.0% actually re-did it or plan to do it for their daughters. EDHS 2008 stated that over the next 15years in Egypt, there will be a steady decrease in the percent of women who will be circumcised from the level of 77% down to 45%.

Conclusion

Recommendation

Conflict of interest

Authors’ contribution

Financial support

Acknowledgments

Introduction
Diabetes mellitus (Type 1 and Type 2) is one of the most commonly encountered diseases by the healthcare professionals. Worldwide, it was estimated that the prevalence rate among adults was 4% in 1995 and this is expected to increase to 5.4% by 2025. Compared to other parts of the world, Kuwait has a higher prevalence of diabetes. In 2010 a study was done and showed that 20% of Kuwaiti population are diabetic. The complications associated with diabetes besides significant mortality are, diabetes-related morbidities such as diabetic retinopathy, neuropathy, and cardiovascular disease. These complications result in a significant morbidity and mortality rate which have placed a heavy financial burden on the society. Healthcare professionals as well as public policy makers are well aware of the public health impact of diabetes.