Post-operative capsular opacification is a multifactorial physiological consequence of cataract surgery. Opacification involving the central posterior capsule has a significant impact on high and low contrast acuity and low contrast sensitivity. The assessment of Posterior Capsule Opacification (PCO) on cadaver eyes, experimental studies, culture models and in clinical studies has provided an understanding of its pathogenesis. The proliferation, migration and abnormal differentiation of residual lens epithelial cells and fibers in the capsular bag have been implicated in the pathogenesis of PCO. The incidence and severity of PCO correlates to the meticulous use of surgical techniques, IOL optic edge designs and IOL materials. This article summarizes the clinical studies with recommendations for retarding the development of central PCO. It discusses experiments with pharmacological agents broadly categorized as anti-inflammatory, immuno-modulating, antiproliferative, antiadhering, antitransdifferentiating agents for the prevention of PCO. These studies will remain critical for future endeavors undertaken for eradication of PCO. Cataract is an opacification of the transparent crystalline lens. The lens is a biconvex, elliptical, semi-solid, avascular body. It is enveloped by a thick capsule, which is a basement membrane of the lens epithelium. The lens epithelial cells (LECs) line the interior surface of the anterior, pre-equatorial, and equatorial regions of the lens capsule Figure . In the Previously in intracapsular cataract extraction, the whole lens along with the entire capsule was extracted. In this method, the LECs are completely removed but there is no capsule left for IOL implantation. In the modern approach to extracapsular cataract extraction, the surgeon extracts all the lens fibers but leaves behind an intact posterior capsule and peripheral anterior capsule of the capsular bag for IOL implantation. Along with the residual capsule, LECs that have the potential to lay down cellular products are also left behind. These again cause opacification, which is referred to as capsular opacification. Thus, capsular opacification is a physiological postoperative consequence of an uneventful uncomplicated extracapsular cataract surgery. Capsular opacification is different from the intraoperative opacification that takes place in the intact lenses. It is known as a plaque which can either be in the anterior and/or posterior capsule. Plaques are frequently associated with white mature cataract .Postoperative capsular opacification can be classified based on its location into anterior and posterior capsule opacification Figure -2E.et al have clinically graded ACO from 0 to IV  placed in the capsular bag . Linear The incidence of PCO is known to range from as high as 50% to as low as <5% in eyes undergoing cataract surgery for uncomplicated senile cataracts -24. PCO Different methodologies have been used in experimental and clinical studies.An examination of human autopsy eyes from the posterior (Miyake-Apple) view, complemented by microscopic analyses is useful in evaluation of IOL-capsular bag interaction, role of the surgical technique, and evaluation of new IOL designs , 29 in rin vitro models have been used to assess the mechanism of PCO formation   as well In the POCOman software, images are analyzed by a set protocol of defining the area of the posterior capsule, removing the Purkinje light reflexes by intensity segmentation, contrast enhancement, filtering to enhance low-density PCO, and variance analysis using a co-occurrence matrix to assess the texture. It provides a semi objective assessment of PCO and is valid and repeatable , 48. TheThese automated image-analysis systems provide an objective PCO assessment and are valuable tools for clinical studies evaluating the development and prevention of PCO. The OSCA is a new system of PCO analysis that incorporates flash detection and removal, registration and subsequent merger of images for artifact removal, as well as location sensitive texture analysis. The system is referred to as the open-access systematic capsule assessment (OSCA) .Another system that captures high resolution images is the EAS-1000 system (Scheimpflug videophotography) . HoweverThe development of PCO is a very dynamic process and involves three basic phenomena: proliferation, migration, and differentiation of residual LECs.in vitro, but little is known about their in vivo effects that lead to PCO  to prevent PCO 2 years after surgery has shown encouraging results  the Anterior Capsule. The overlap of the anterior capsule rim over the IOL optic leads to the EMT of the LECs, resulting in ACO. Several authors have evaluated the role of polishing the anterior capsule on the development of PCO when using silicone IOLs. Polishing of the anterior capsule has been effective in reducing fibrotic opacification but ineffective in reducing regeneratory opacification , naphtyl urea suramin  (hibitor)  and lipohibitor) . Inducinhibitor) , fas lighibitor) , ricin Ahibitor) , ricin Ahibitor) , and 1% hibitor) . Adenovihibitor) . Indocyahibitor) , 141.The drugs can be delivered within the capsular bag to the residual LECs by coating the IOL, modifying the irrigating medium, and during cortical cleaving hydrodissection, majority of which are still in the experimental phase.Coating the IOL. The delivery via the IOL could provide a more controlled means of drug delivery that can concentrate an agent at the site of the potentially proliferating cells more efficiently. A heparin coated PMMA IOL reduces inflammation and the incidence of PCO  laser capsulotomy. Figures in vitro experiment of human capsules with a central hole of 5 mm (PCCC) placed in a culture showed that even in the absence of the posterior capsule, their natural substrate, LECs that remain after cataract extraction have the potential to proliferate and form a monolayer of LECs on a basal lamina of vitreous origin. These LECs are able to close the posterior capsulorrhexis partially or totally in approximately one-third of cases (Children display a significantly higher incidence of postoperative PCO and a higher Nd: YAG laser posterior capsulotomy rate . In chilof cases .et al have suggested anterior and posterior vertical capsulotomy, with optic entrapment of the intraocular lens to avoid vitrectomy in infants under the age of 5 years. The fusion of the anterior and posterior capsules in front of the IOL limits the proliferation and migration of Elschnig pearls (In children, multiquadrant cortical cleaving hydrodissection ensures thorough, complete, easy, and rapid removal of the nucleus in eyes with an intact capsule . Primaryg pearls .In younger children, visual axis obscuration due to PCO can be treated with pars plana vitrectomy and membranectomy. In older children and adults an Nd: Yag posterior capsulotomy is an acceptable option for the management of PCO . RetinalIn conclusion, capsular opacification, in particular, PCO, still remains a physiological complication of an uneventful cataract surgery. The quest for its eradication goes on. Different patient-related factors, ocular and systemic conditions, surgical techniques to remove the residual LECs, and residual cortical fibers and adjuncts influence the development of PCO. The use of intraocular lenses with different biomaterials and edge designs can influence the progression of visually significant PCO. At present, meticulous use of surgical techniques and appropriate intraocular lens remain the mainstays for retarding the development of post-operative posterior capsule opacification in humans.


Nairovirus, family Bunyaviridae, and congaing a three segment single-stranded RNA genome. The CCHFV is transmitted to humans by bite of infected ticks, by direct contact with blood or tissues of infected livestock and nosocomially. After Chaharmahal-va-Bakhtiari outbreak in 1999 whose serum samples was sent to South Africa for diagnosis, Arboviruses and Viral Hemorrhagic Fevers Laboratory  was established in 2000 to precise and on time laboratory diagnosis of CCHF in the country. The Lab along with CDC of Iran  and Veterinary organization (control program of tick populations and livestock monitoring) are members of National Expert Committee on Viral Hemorrhagic Fevers (NECVHFs) for surveillance and control of CCHF in Iran.Crimean-Congo Hemorrhagic Fever (CCHF) is a viral zoonotic disease with high mortality rate in humans caused by CCHF virus (CCHFV) belonging to the genus Since the establishment of the laboratory as National Ref. Lab, probable human sera, suspected livestock sera and tick samples were analyzed by serological (IgM and IgG ELISA) and molecular  assays.As our result show, the mortality rate of CCHF in the country has been declined in the recent years compared with the early year. Regarding transmission route, most important route of transmission has been through close contact with blood and tissue of infected livestock, so the highest proportion of CCHF infection has been seen in high risk professions such as slaughterers, butchers, farmers. By considering geographical distribution, Sistan-va-Baluchistan not only ranked the most infected province in Iran, but also, the infection has been seen in all years. On the other hand, other most infected provinces included Isfahan, Fars, Khorasan and Yazd respectively, although CCHF infection has been seen in 23 out of 30 provinces of the country. Concerning sex distribution, males are infected with triple times as much as females. Also, in age distribution the disease has been prevalent in age range of 21-40 years old. The CCHFV genome was detected in tick populations collected from different high risk areas. With respecting genetic analysis, Our phylogenetic studies on CCHFV genome extracted from human and tick demonstrated that the Iranian strain have had close relationship with Pakistani (Matin) strain and the genome extracted from both hosts were very similar altogether.With efficient trainings for high risk professions, the mortality rates can be decreased in high risk areas. In addition, control and prevention programs such as tick population control may address the decline of the CCHF disease in endemic regions and to block its prevalence to other regions of the country. Lastly, import of livestock to the country should be monitored and population of livestock and tick in high risk areas and endemic regions should be always surveyed with serological and molecular epidemiology. With different data on mortality rate in different endemic regions, more pathogenesis and phylogenetic analysis should be performed.


The steroid hormones generate myriad effects through several well-known mechanisms of action. Beyond the physiological function of steroid hormones, the steroid-like effects of some natural and synthetic compounds have led to the promising field of alternative therapies. However, to these new compounds, the molecular, subcellular, and cellular signal transductions need to be elucidated. Although new questions about the relevance of multiple targets of action for exogenous compounds are deeply in discussion, the original contributions that depict novel insights into basic and clinical aspects with perspectives on medical application are welcome.This special issue compiles papers from renowned research groups in the world that cover the frontiers of the latest findings on steroids and related compounds effect, mechanism of action and its relevance on carcinogenesis, immune suppression, and osteoporosis, as well as novel steroidal glycosides characterization. The papers on sex steroids hormones review the role of progesterone  and related progestins compounds in hepatocellular carcinoma. The authors highlight that the higher incidence of hepatocellular carcinoma in men than women might have resulted from the stimulatory effects of androgen and the protective effects of estrogen and also eventually suggest a new insight into the associations of progesterone and related compounds with hepatocellular carcinoma development and treatment. Also, the sex steroid hormones in the modulation of bacterial-host interactions were revised since the dimorphic sex difference  is mainly due to the differential modulation of the immune system by sex steroid hormones through the control of proinflammatory and anti-inflammatory cytokines expression, as well as Toll-like receptors expression and antibody production.Some interesting studiesonhumans addressed the effect of chronic glucocorticoid therapy on osteoporosis in children with 21-hydroxylase deficiency as much to replace congenital deficits in cortisol synthesis as to reduce androgen secretion by adrenal cortex. As consequence, a secondary osteoporosis is formed. It results in an early, transient increase in bone resorption accompanied by decrease in bone formation, maintained for the duration of glucocorticoid therapy. Based on conflicting results from the literature about the bone status on glucocorticoid-treated patients with 21-hydroxylase deficiency, the authors point that the monitoring of the bone status of these patients, checking bone mineral density and bone turnover markers, and studying the expression of regulators of bone resorption should be useful in order to avoid glucocorticoid-induced osteoporosis in adulthood. Also, based on many epidemiological studies concerning the inverse relationship between isoflavone intake and bone loss and fracture rate, some substances on serum levels after food intake indicated for patients with osteopenia/osteoporosis were analyzed. Concerning genistein bioavailability, it was deeply discussed that, beyond the intestinal bacteria, solubility and permeability, glucosidase activity, viscosity induced by food additives, and a multitude of transporters on luminal intestinal cells for absorption, several factors from the diet composition influence the net absorption of single entity and also the effectiveness of the bone build. So, with these data in mind, the bioavailability of genistein depends on specific ingredients and excipients in each formulation which can interfere with absorption and could have clinical implications on efficacy. 21 steroidal glycoside, anhydrohirundigenin monothevetoside, were isolated from the roots of Cynanchum stauntonii (Decne.) and extensively evaluated by spectroscopic analyses, mainly 1D and 2D NMR, HRESI-MS and chemical methods. It is known that C21 steroids and their glycosides are of considerable bioactivities, such as hypolipidemic and antitumor activity. So the enriched information about C. stauntonii as a significant source of steroidal glycosides deserves careful phytochemistry investigation as well as the classification of bioactive compounds to be proposed as nutraceutical agents interesting both to academy and industry and also to specific therapy option.The ongoing investigations of some groups in the world have characterized new steroidal compounds from plants with medicinal interest. Three new steroidal glycosides, named as stauntosides L, M, and N, along with one known C


Kidney disease associated with diabetes mellitus is a major health problem worldwide. Although established therapeutic strategies, such as appropriate blood glucose control, blood pressure control with renin–angiotensin system blockade, and lipid lowering with statins, are used to treat diabetes, the contribution of diabetic end-stage kidney disease to the total number of cases requiring hemodialysis has increased tremendously in the past two decades. Once renal function starts declining, it can result in a higher frequency of renal and extra-renal events, including cardiovascular events. Therefore, slowing renal function decline is one of the main areas of focus in diabetic nephropathy research, and novel strategies are urgently needed to prevent diabetic kidney disease progression. Regardless of the type of injury and etiology, kidney fibrosis is the commonly the final outcome of progressive kidney diseases, and it results in significant destruction of normal kidney structure and accompanying functional deterioration. Kidney fibrosis is caused by prolonged injury and dysregulation of the normal wound-healing process in association with excess extracellular matrix deposition. Kidney fibroblasts play an important role in the fibrotic process, but the origin of the fibroblasts remains elusive. In addition to the activation of residential fibroblasts, other important sources of fibroblasts have been proposed, such as pericytes, fibrocytes, and fibroblasts originating from epithelial-to-mesenchymal and endothelial-to-mesenchymal transition. Inflammatory cells and cytokines play a vital role In the process of fibroblast activation. In this review, we will analyze the contribution of inflammation to the process of tissue fibrosis, the type of fibroblast activation and the therapeutic strategies targeting the inflammatory pathways in an effort to slow the progression of diabetic kidney disease. Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) worldwide . CurrentTherefore, in an effort to aid in the discovery of novel therapeutic concepts that allow the prevention and retardation of diabetic nephropathy, innovative insight into the pathophysiology of diabetic nephropathy is mandatory . HemodynVarious theories have been proposed concerning the pathogenesis of diabetic nephropathy, including proteinuria, genetics, race, hypoxia, ischemia, and inflammation . IndividThe role of inflammation in diabetic nephropathy has been reported previously . In the Various theories have been proposed regarding the development and progression of diabetic kidney disease. The pathological events that have traditionally been implicated in the development of diabetic nephropathy include poor glycemic control, hypertension, proteinuria, and other such factors. Individual factors such as genetics, race, obesity, and smoking have been shown to contribute to variations in the onset and progression of kidney disease .Diabetic organ damage, including diabetic nephropathy, is fundamentally triggered by glucose metabolism defects; normalizing blood glucose levels is essential for diabetic therapy . Indeed,The degree of urine albumin/protein is associated with the progression of kidney disease via the activation of tubular angiotensin-converting enzyme (ACE) inhibitors or inflammatory pathways . StrategSystemic/intra-glomerular hypertension can result in the onset and progression of diabetic kidney disease. ACE inhibitors and angiotensin receptor blockers (ARBs) have been shown to slow disease progression by controlling hypertension, in addition to decreasing proteinuria . Non-dihDiabetic insults to the kidney are mediated through the various pathogenic pathways described above. Inflammation appears to be the final common pathway and can result in either kidney repair if regulated or fibrosis if the process is uncontrolled.Fibrosis is a sequence of normal wound healing and repair that is activated in response to injury to maintain the original tissue architecture and ensure normal functional integrity . EssentiOnce tissue is injured, inflammatory cells infiltrate the site of injury due to the enrichment of pro-inflammatory niches at the site of injury and directional guidance mediated by chemotactic cytokine concentration gradients . The infTable 1; The importance of inflammation in the development and progression of renal fibrosis has been well documented Table 1; . Inflamm+ T cells were depleted in wild-type mice after obstructive injury  mice led to restored fibrogenic responses following obstructive injury  structures  and are often referred to as myofibroblasts. These types of cells possess unique contractile properties . In the Figure 1 briefly summarizes the five well-reported sources of matrix-producing myofibroblasts, including the activation of residential fibroblasts, differentiation of pericytes, recruitment of circulating fibrocytes, and conversion of tubular epithelial cells and endothelial cells into mesenchymal cells . This concept has recently been debated and challenged . The myofibroblast phenotype is indeed a mixture of both matrix component-producing activated fibroblasts and αSMA-expressing highly contractile smooth muscle cells.Fibroblasts are localized in the interstitial space between the capillaries and the epithelia in normal kidneys. They are organized as a network spread throughout the renal parenchyma, where they stabilize and organize the tissue architecture . MorpholFibroblasts become activated by stimulation with cytokines, including TGF-βs, connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), and fibroblast growth factor 2 FGF2; . In addiTissue-type plasminogen activator (tPA), which can also be derived from activated macrophages, is another critical factor in kidney fibrosis . tPA plaFigure 2; Some studies have suggested that vascular pericytes are a major source of myofibroblasts in fibrotic kidneys . However+ monocytes , which is the extreme outcome of EMT . The number of epithelial cells undergoing EMT does not necessarily need to be identical or even similar to the number of cells that become fibroblasts  inhibits NFκB, thereby inhibiting MCP-1 . PioglitIn view of the current understanding of the central role of inflammation in diabetic nephropathy progression, future studies may focus on maintaining epithelial integrity, halting the process of EMT/EndMT transition and controlling the cytokine milieu.Future diabetic nephropathy research could be directed toward inhibiting the inflammatory pathway in conjunction with conventional therapeutic strategies , althougDiabetic nephropathy is a devastating kidney disease that contributes to the majority of end-stage kidney disease cases worldwide, and this condition is associated with a higher frequency of cardiovascular events. Diabetic nephropathy is associated with the activation of a variety of pathways that lead to the progression of kidney disease. Among these pathways, inflammatory pathway activation plays a central role. The inflammatory pathway leads to the activation and recruitment of the fibroblasts, which in turn initiate and sustain the fibrotic process. Apart from conventional glucose control and blood pressure control, targeting the specific pathways that lead to the activation of inflammation and fibroblasts could be a new and effective intervention in the management of diabetic nephropathy.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Food allergy is the most common cause of anaphylaxis outside the hospital setting. Peanut, tree nuts, milk, egg, and shellfish are the most commonly implicated foods. Most cases of anaphylaxis are reported to occur in the home, but one-fifth of the reactions occur at school or work and a similar proportion in restaurants and other food establishments. Although the majority of reactions in schools occur in subjects with known food allergies, nearly 25% of peanut/tree nut-induced allergic reactions were reported before the diagnosis. The majority of reactions occur in the classroom (many due to craft projects), followed by health office, playground, and cafeteria. Numerous studies have identified deficiencies in establishing and implementing written emergency action plans (EAP) and general or individualized plans for prevention in schools, and inadequacies in recognizing and treating anaphylaxis. Although there are no studies directly comparing the effect of banning peanut schools on the incidence of reactions, such practice from preschool to lower elementary school is not uncommon. Reactions to nuts occurring in food establishments most commonly include Asian food restaurants, ice cream parlors and bakeries/dough nut shops. Allergen is commonly found in dessert foods or hidden in sauce, dressing etc. Cross-contamination during preparation and serving is another important source of error, in addition to reactions due to ingestion of food not intended for the subject, buffet items, or casual contact. Importantly, the establishment is often not notified of the allergy. Lack of timely treatment with epinephrine is a universal risk factor and adolescents/young adults are the peak age group for a fatal food-induced anaphylaxis. Furthermore, up to one-fifth of food-induced anaphylactic reactions may need more than 1 dose of epinephrine. Therefore, there is an urgent need for education and access to epinephrine in food-induced reactions occurring in the communal setting.


Much progress has been made in recent years toward understanding the underlying causes of neurodevelopmental disorders. Whereas catastrophic failures in early events such as cell fate specification or cell migration give rise to profound developmental defects including microcephaly and lissencephaly, more subtle conditions such as autism, intellectual disability or neuropsychiatric disorders increasingly appear to result from comparatively minor changes in neural circuit formation and function. The formation of proper neuronal circuitry relies on later developmental processes such as axon guidance, the arborization both of axons and their target dendrites, the recognition of appropriate synaptic partners, the establishment and maturation of synaptic connections, and the subsequent elimination of improper connections. The research topic presented here, “Mechanisms of Neural Circuit Formation,” addresses recent advances in our understanding of the cellular and molecular bases of these processes.The papers in this volume generally fall into three broad areas of developmental neurobiology, including new techniques for the study of these processes: (1) cell adhesion molecules (CAMs) and their downstream roles in cell identity, recognition, and synaptic specificity; (2) axon guidance, formation of terminals, and dendritic arborization; and (3) formation of synaptic structures themselves, the essential final step in circuit formation which, nevertheless, remains subject to remodeling and plasticity throughout development and even in adult animals.The volume opens with a review by Sokolowski and Corbin , highligThis last paper transitions into a section focused on axon guidance, including both signaling and cytoskeletal mechanisms. Sakai and Kaprielian  review tThe penultimate group of papers concerns mechanisms regulating the formation of pre-and post-synaptic structures. The assembly and plasticity of the presynaptic active zone is reviewed in Clarke et al. . A revieThe E-book closes with two papers describing powerful new techniques for studying neural circuit formation that are revealing novel biology both in Drosophila, as described by Nose , and in Together, these papers provide a broad reflection of the state of our knowledge concerning the molecular cues that direct axon and dendrite development, promote the formation of synaptic connections, and allow the refinement of connectivity and plasticity during development. An interesting observation that comes from these studies is that few, if any, of the key molecules are single-purpose; each pathway is used at distinct stages of neural development and serves multiple functions. The extent to which these functions relate varies. For example, semaphorins broadly influence both axonal and dendritic development, perhaps not surprisingly given the large number of different ligands and receptors involved. Fibroblast Growth Factor family members (FGFs), critical players in a wide variety of developmental events in the early embryo, are much later re-purposed to regulate the formation of synaptic circuitry. CAMs like the γ-protocadherins and DSCAMs, regulate several key processes, including neuronal survival, dendrite arborization, and axonal targeting; here, it remains unclear whether these functions are achieved through common signaling pathways, or whether they represent distinct roles for these CAMs. Thus, despite the daunting complexity of the task, the cast of key players is not increasing as rapidly as the number of roles assigned to each cast member. This could facilitate future progress by focusing efforts on a smaller number of molecules. Conversely, efforts could be complicated by the need to dissect primary and secondary effects for each pathway. This highlights the need to be particularly rigorous in defining where, when and how the functions of these proteins are analyzed. As the methods and specificity of these analyses improve, so will our understanding of neural circuit formation.Considering the finely-tuned complexity of the mature nervous system, the robustness of neurodevelopment is amazing; despite genetic and environmental variability during development, and the stochastic variation inherent in biological systems, most brains end up working pretty well. The experimental investigation of small circuits and defined aspects of neural circuit formation is facilitating progress in this area, as the papers in this volume demonstrate. However, a key challenge for the future is to integrate the information we are gaining on individual molecular pathways into a larger model in order to understand how the neural circuitry of the mature nervous system is assembled during development.


Petrography and physicomechanical properties of alkali granites, alkali quartz syenite, and nepheline syenite from Ambela, NW Pakistan, have been investigated. Whereas the alkali quartz syenite and most of the alkali granites are megaporphyritic, the nepheline syenite and some of the alkali granites are microporphyritic. Their phenocryst shape and size and abundance of groundmass are also different. The values of unconfined compressive strength (UCS) are the lowest and highest for megaporphyritic alkali granite and alkali quartz syenite, respectively. However, all the four rock types are moderately strong. Correspondingly, their specific gravity and water absorption values are within the permissible range for use as construction material. The UCS for the alkali quartz syenite is the highest, most probably because (i) it has roughly equal amounts of phenocryst and groundmass, (ii) it displays maximum size contrast between phenocryst and groundmass, (iii) its phenocrysts are highly irregular, and (iv) it contains substantial amounts of quartz. The middle to late Paleozoic Ambela Granitic Complex (AGC) is a part of the Peshawar plain alkaline igneous province (PPAIP) –3 and liThe northern part of Pakistan consists of (i) the Eurasian plate in the north, (ii) Kohistan island arc in the middle, and (iii) Indo-Pakistan plate in the south , 7. The The AGC consists of silica oversaturated (70%), silica saturated (20%), and silica undersaturated rocks (5%) and dykes (5%). These are classified into three groups on the basis of modal mineralogy . Group 1Fresh  bulk and fist-sized rock samples were collected. Two of the four bulk samples collected for determining physicomechanical properties represent alkali granites from Ambela proper, while the remaining two include one each of quartz syenite from Babaji Kandao and nepheline syenite from Koga area . Thin seFor determining mechanical properties, two cylindrical core samples were obtained from each of the bulk samples with the help of a core drilling machine in the Rock Mechanics laboratory of the Department of Mining Engineering, NWFP University of Engineering and Technology, Peshawar, Pakistan. All the core samples were subjected to (i) unconfined compressive strength (UCS), (ii) unconfined tensile strength (UTS), and (iii) shear strength. Besides, specific gravity and capacity of water absorption of all the bulk samples were determined in the Geochemistry Laboratory of the National Center of Excellence in Geology, University of Peshawar, Pakistan.Fifteen representative rock thin sections were used for a detailed petrographic investigation including structural/textural characteristics, identification of the constituent mineral phases, and determination of modal mineralogical composition through visual estimation. Based on these details, the studied rocks are distinguished into the following types.Investigation of nine representative thin sections leads to a further subdivision of the alkali granite into two textural types: (i) megaporphyritic and (ii) microporphyritic.On the basis of the relative proportions (volume %) of the three essential minerals, that is, perthitic alkali feldspar (50–55%), quartz (28–33%), and plagioclase (2-3%), these largely hypidiomorphic and inequigranular to subequigranular rocks fall within the compositional field of alkali feldspar granite . A varieThe alkali feldspar, including microcline, is mostly perthitic and occurs as megacrysts that occasionally display simple twinning Figures . MicrofrThis inequigranular (to subequigranular) rock is hypidiomorphic to allotriomorphic. Perthitic alkali feldspar (41-42%), quartz (40–42%), and plagioclase (2-3%) are their essential constituents while biotite, garnet, muscovite, apatite, sphene, and zircon are the commonly occurring accessory minerals. In addition to being finer grained, the rock under discussion shows significantly higher quartz to feldspar ratio than the one described above . Most ofInvestigation of three thin sections suggests that this rock predominantly consists of perthitic alkali feldspar , which occurs in two distinct grain-size populations, namely, coarse-grained and medium to fine grained. The latter together with microcline, quartz (8–10%) and plagioclase (1-2%) constitutes the matrix to the megacrysts/phenocrysts that almost totally consist of perthite. Amphibole, biotite, opaque ore mineral, sphene, epidote, and aegirine augite are the commonly occurring mafic minerals, which collectively constitute about 25% by volume of the rock. Of these, amphibole is one of the major constituents and mostly the second most abundant mineral (averaging ~12%). The abundance of sphene is also substantial (4-5%) while all the other mafic minerals and carbonate (1-2%) occur in minor-to-accessory amounts. Apatite, zircon, monazite, and fluorite occur in traces.The total abundance of mafic minerals and feldspar to quartz ratio in the porphyritic alkali quartz syenite is distinctly higher but micas much less abundant than in alkali granites. The alkali quartz syenite shows close similarity to the megaporphyritic alkali granite in terms of the form and size of grains and other textural features of perthitic alkali feldspar and plagioclase. However, perthite is largely unaltered in the former type.Quartz largely occurs as fine- to very fine-grained groundmass and along the boundaries of perthite. Aggregates of very fine-grained quartz occur in association with biotite, anhedral sphene, and amphibole Figures . Fine glStudy of three representative thin sections reveals that the nepheline syenite essentially consists of alkali feldspar (54–57%), nepheline (14–16%), hornblendic amphibole (6–9%), sphene (5-6%), plagioclase (4-5%) and aegirine augite (4-5%). The commonly occurring accessory minerals include biotite, opaque ore mineral, apatite, zircon, and monazite. All the nonfelsic minerals collectively constitute about 25% by volume of the studied samples. Both the amphibole and pyroxene show alteration into chlorite and/or epidote.The alkali feldspar (and to a less extent microcline) is largely medium grained and occurs as tabular and mostly subhedral perthitic grains showing the effects of kaolinization. Some of the perthitic alkali-feldspar grains show simple twinning. Nepheline is medium to fine grained and euhedral to subhedral in form. It also occurs in crystals with prismatic habit. The margins, shape, and disposition of nepheline grains as well as those of perthite and plagioclase suggest that the rock has been deformed .The UCS and UTS of the petrographically investigated samples of alkali granites, alkali quartz syenite, and nepheline syenite were determined in the laboratory. Besides, the values of shear strength were also worked out. UCS and UTS were measured directly by strength testing machine while cohesion and angle of internal friction, which collectively determine shear strength, were derived from the values of UCS and UTS. Relevant information including definitions of these various tests and details regarding the nature and preparation of samples and different methods used for their determination and calculation has been outlined elsewhere .Two core samples per bulk sample were used for determining the UCS and UTS. The values of UCS of all the studied rocks, including even the megaporphyritic alkali granite whose UCS value is the lowest, are high enough  is distinctly higher than the alkali granite . Whereas the most abundant mafic phases in the alkali granites are biotite and opaque ore mineral, amphibole and sphene constitute the same in both the alkali quartz syenite and nepheline syenite. It should be noted, however, that mica flakes in the studied samples do not display any alignment and mostly occur in patches together with the other mafic minerals.Although significantly different from one another, the UCS values of all the studied rocks fall within the range of those designated as moderately strong . SimilarThe generally agreed upon geotechnically important features of rocks include (i) modal mineralogical composition, (ii) grain size and extent of its variation, (iii) grain shape, (iv) the overall abundance of flaky minerals (mica) and, more importantly, the degree of their preferred orientation, and (v) degree of weathering or alteration , 17–21. As all the investigated rocks represent the same area and igneous activity of broadly similar age, they would hardly, if at all, differ in terms of their degree of weathering/alteration. The thin section observation also precludes any significant weathering or alteration of the studied samples. The general scarcity and more importantly the random orientation and patchy distribution of micas in the studied rocks eliminate any possible adverse effect on their strength and mechanical properties due to the fourth of the factors listed above. In other words, the difference in the values of UCS, specific gravity, and water absorption of the investigated samples can only be ascribed to differences in their modal mineralogy and texture.The UCS values of the investigated rocks appear to be depending more on grain size than modal mineralogy. That is why the samples of alkali granite with broadly similar mineralogical composition but different phenocryst size have different values of UCS. The alkali granite with medium- to fine-grained phenocrysts is stronger (UCS = 35.849–39.622 MPa) than the alkali granite with very coarse-grained phenocrysts (UCS = 27.672–30.817 MPa). However, the UCS of alkali quartz syenite is the highest (47.169-45.911 MPa) although its average phenocrysts' size is comparable to that of the very coarse-grained alkali granite. Similarly, although the average size of phenocrysts in the nepheline syenite sample is the smallest (fine to medium), yet its UCS is low (30.188–34.591 MPa) and higher only than the alkali granite containing very large phenocrysts.The difference between the average size of phenocrysts and that of the groundmass in individual samples increases from the mega-porphyritic alkali granite through nepheline syenite to quartz syenite. This is also the order of increase in the UCS values. Again, however, there is an exception; that is, the sample of alkali granite with medium- to fine-grained phenocrysts does not follow the otherwise positive relationship between the UCS and the grain size contrast between the phenocryst and the groundmass.The ratio in the proportion of phenocrysts to matrix does not vary systematically with UCS. This ratio is the highest for the mega-porphyritic alkali granite and the lowest for the nepheline syenite. On the other hand, the UCS value of quartz syenite is the maximum, although the ratio between its phenocryst and matrix abundances is intermediate. Also, the alkali granite with medium- to small-sized phenocrysts and minimum phenocrysts to matrix ratio, like the mega-porphyritic alkali granite, has its UCS higher than both the latter and the nepheline syenite.The irregularity displayed by the phenocryst shapes in quartz syenite is higher than that in both the mega-porphyritic and microporphyritic types of the alkali granite but comparable to that in nepheline syenite, which is fine to medium grained. Hence the strength of the studied rocks does not show any systematic variation with the degree of irregularity of their phenocrysts.Hence it follows that none of the petrographic parameters independently controls the strength of the rocks investigated. Rather, a number of petrographic features appear to have collectively contributed to determine the actual rock strength. Thus the sample of quartz syenite shows the highest UCS most probably because (i) it contains roughly equal amounts of groundmass and phenocryst, (ii) the gain size of its groundmass is finest and thus it displays the maximum contrast in the grain size of its phenocryst and groundmass components, (iii) the shapes of its phenocrysts are highly irregular, and (iv) it contains substantial amounts of quartz. It is important to mention that although the sample of nepheline syenite is comparable to quartz syenite in terms of the first and third of these features, yet its UCS is lower than that of the latter probably because (i) it is totally devoid of quartz and (ii) it displays less contrast in the grain size of its phenocryst and groundmass components .


Odobenus rosmarus divergens) are diminishing resulting in altered walrus behavior, mortality, and distribution. I document changes that have occurred over the past several decades and make predictions to the end of the 21st century. Climate models project that sea ice will monotonically decline resulting in more ice-free summers of longer duration. Several stressors that may impact walruses are directly influenced by sea ice. How these stressors materialize were modeled as most likely-case, worst-case, and best-case scenarios for the mid- and late-21st century, resulting in four comprehensive working hypotheses that can help identify and prioritize management and research projects, identify comprehensive mitigation actions, and guide monitoring programs to track future developments and adjust programs as needed. In the short term, the most plausible hypotheses predict a continuing northward shift in walrus distribution, increasing use of coastal haulouts in summer and fall, and a population reduction set by the carrying capacity of the near shore environment and subsistence hunting. Alternatively, under worst-case conditions, the population will decline to a level where the probability of extinction is high. In the long term, walrus may seasonally abandon the Bering and Chukchi Seas for sea-ice refugia to the northwest and northeast, ocean warming and pH decline alter walrus food resources, and subsistence hunting exacerbates a large population decline. However, conditions that reverse current trends in sea ice loss cannot be ruled out. Which hypothesis comes to fruition depends on how the stressors develop and the success of mitigation measures. Best-case scenarios indicate that successful mitigation of unsustainable harvests and terrestrial haulout-related mortalities can be effective. Management and research should focus on monitoring, elucidating effects, and mitigation, while ultimately, reductions in greenhouse gas emissions are needed to reduce sea-ice habitat losses.The extent and duration of sea-ice habitats used by Pacific walrus ( Odobenus rosmarus divergens) interactions specifically. All these assessments noted a lack of baseline as well as current data for many marine species, ecosystems, and processes that would be useful in assessing climate change effects.Arctic and subarctic regions are disproportionately affected by current climate warming that appears to be driven by anthropogenic greenhouse gas emissions . As the seasonal dynamics of ice cover on arctic seas change, many marine mammals are being affected to various degrees .Several marine mammals are adapted to arctic sea-ice dynamics  describe environmental changes over the last 20–30 years, how those changes influence a number of stressors, and walrus responses to those changes; and (2) predict how those stressors will develop and how walrus will respond out to the end of the 21st century, after a brief review of Pacific walrus ecology and behavior. Because the future intensity of many stressors is dependent on economic forces, policy responses, and the efficacy of mitigation programs, we integrate the results of a scenario analyses outlined in MacCracken et al.  into fouPacific walrus are closely associated with the annual formation and melting of sea ice. Walrus feed primarily on benthic invertebrates  and rest on sea ice or shore  between Many adult male walruses remain in the Bering Sea during summer and forage from haulouts along the mainland coast of the Russian Federation and United States  of 250,000–300,000 + walruses based on population estimates , and prePacific walrus have been hunted for subsistence for millennia, which continues today, commercially since the 17th century Fay  until 19In the 1960s, the State of Alaska and the Union of Soviet Socialist Republics implemented harvest restrictions , derived from passive microwave satellite data, reaches a minimum in September which has been declining over the past 30 years by about 9%/year, with the record low set in 2007 and comparable lows occurring again in 2008, 2010, and 2011 .There are two concentrations of Pacific walrus during the summer in the Chukchi Sea when ice is present over the continental shelf Fay , one immThere are two primary stressors associated with the recent trend of sea-ice loss from shallow continental shelf areas of the Chukchi Sea; (1) animals that stay with the sea ice as it moves over the Arctic basin cannot feed and become emaciated and weak before eventually abandoning the ice for the coast, and (2) mortalities due to crushing of young animals at coastal haulouts can number in the hundreds to thousands . The absorption of carbon dioxide by seawater reduces the concentration of aragonite, which is important in the Arctic because clams, mussels, snails, crustaceans, and some plankton use aragonite in their shells and exoskeletons  through the Bering Strait increased by 7–423% from 2009 to 2010, with the largest increase occurring west of the international dateline . The U.S. Coast Guard is currently assessing potential commercial ship routing through the Bering Strait region (United States Coast Guard [USCG] 2010) which will be considered in the development of regulations to govern shipping in United States waters. In addition, the Russian Federation complies with a number of voluntary guidelines, but is not a party to other agreements , best-case (Sbc), and worst-case (Swc). The most likely-case represents scenarios judged to be the most plausible; the best-case and worst-case scenarios are less likely to occur; however, one or the other often aligned closely with the most likely-case (Science [1965]). In short, Chamberlin advocated the development and consideration of all plausible and rational hypotheses that potentially explain new phenomena to counteract biases introduced through a singular focus on a “ruling hypothesis” or a “single working hypothesis”. Chamberlin's  is predicted to decline (from a 1979–2008 baseline) about 4% by mid-century and 20% by late-century, resulting in a 1- and 3-month increase in the number of ice-free months, respectively. The position of the ice edge does not move north appreciably until late-century . The mosbc: these processes may result in little change or a small-moderate overall decline in benthic invertebrates that will be suitable as walrus prey. Swc: alternatively, changing ocean conditions could lead to the extirpation of the majority of preferred prey and species that may fill those vacant niches may not be suitable as walrus prey. Due to a lack of detailed and current information on walrus prey, a most likely-case scenario could not be developed for this stressor.There are indications of a decline in benthic mass in the Bering Sea  in the Chukchi Sea as well as the recent northward expansion of crabs and a bivalve from the North Pacific. However, as for the Bering Sea, the effects of temperature increases and OA on specific walrus prey species have not been studied. If OA and temperature changes in the Chukchi Sea affect walrus prey, there will most likely be changes in species composition and abundance as postulated for the Bering Sea; however, the data of Sirenko and Gagaev  cover the range of plausible future conditions based on the cumulative effects of the stressors and result in divergent outcomes. Other potential scenarios considered incorporated small and subtle changes in the intensity of one or a few stressors, and they would fall within the bounds of these hypotheses. Because of the intricacies of each hypothesis, I did not attempt to determine a most likely-case, but it should be apparent which would represent best-case and worst-case scenarios.The following working hypotheses , foraging from fall haulouts limits the population, subsistence harvest remains stable, resource developments increase but are mitigated, and no large industrial accidents occur. Under this hypothesis, the population will decline to a level dictated by prey resources that can be accessed from fall coastal haulouts and most likely fluctuate at that level. The information needed to reliably predict the rate or magnitude of the population decline is not available. Three areas of major uncertainty in this scenario are the effects of OA and temperature on walrus prey, harvest sustainability, and the effects of an industrial accident.WH2: sea-ice predictions for 2099 occur by mid-century, the northward shift in walrus distribution increases, fall coastal haulout use increases in frequency and duration, frequent large mortality events occur at haulouts, foraging from summer-fall haulouts limits the population and OA and temperature increases further reduce walrus prey, subsistence harvest becomes unsustainable due to a large and rapid population decline, resource developments increase, and impacts are inadequately mitigated. Under this hypothesis, I expect the population to decline to a point where the probability of extinction increases substantially.WH3: under either of the above hypotheses, over the long-term walruses eventually migrate from the Bering and Chukchi Seas to sea-ice refugia in the eastern Siberian-Laptev Seas and the Canadian Arctic where the population either stabilizes at the carrying capacity of those areas or declines to lower numbers.WH4: economic forces, technological advances, and policy changes result in reduced greenhouse gas emissions, sea-ice dynamics moderate and ice recovers over the next few decades  and affect walrus prey may also become important.http://www.arcus.org/search/siwo). This program provides weekly updates on ice distribution and 5- to 10-day forecasts of sea ice and weather conditions to assist walrus hunters and other community members. In addition, the EWC began an annual post-hunt survey of its Commissioners in 2006 that provides information on habitat changes and walrus behavior, physical condition, abundance, etc. that informs management programs. Furthermore, changes in the walrus co-management program, including management before depletion, as suggested by Metcalf and Robards (Many Alaskan and Chukotkan coastal communities continue to be closely tied to the Pacific walrus in many ways EWC . Changes Robards  and Roba Robards  may also Robards  not onlyContaminant levels in the Arctic may increase due to climate change through increased mobilization, temperature accelerated chemical reactions, exposure of buried wastes due to coastal erosion and contaminants stored in the ice pack, permafrost, and vegetation, industrial accidents, and an overall increase in human activities, etc. USFWS . The effPacific walrus face many challenges associated with a warming climate. Palaeological evidence suggests that they survived past warming events in situ or through migration to Arctic sea-ice refugia (Dyke et al. High levels of greenhouse gas emissions are the ultimate cause of the changes that are impacting Pacific walruses. Regardless of how the climate changes in the future, programs that reduce the probability of large mortality events at fall coastal haulouts need to be continued, enhanced, and expanded. In addition, harvests need to continue to be closely monitored, struck and lost rates reduced, and methods to reliably assess the sustainability of the harvest developed. For impacts related to stressors that have yet to materialize, for example, OA, I have identified plausible scenarios that can guide monitoring and research programs and some potential mitigation actions.


Multiple symmetrical lipomatosis, or Madelung's disease, is a rare disease of unknown etiology. It is characterized by the presence of loose adipose tissue deposits localized in the cervical region and in the upper body. The neoformations grow slowly and their initial consequence is purely esthetic. They can, however, lead to compression of the laryngotacheal area and of the esophagus. This disease usually affects middle-aged males from the Mediterranean area with a history of alcohol abuse. Although most cases have been sporadic, a few authors have indicated that the disorder may be hereditary. It is thought that this pathology originates from an alteration in lipid metabolism. Since the patients were asymptomatic temperance and diet was proposed, surgical removal of the lipomatose mass is the treatment of choice in case of complications due to fat mass compression on upper aerodigestive tract. The authors present three cases of Madelung's disease with different and particular manifestations. Multiple symmetric lipomatosis (MSL) is a rare disease also known as Madelung's disease, Launois-Bensaude syndrome, and benign symmetric lipomatosis. The disorder was first described by Brodie in 1846 , 3.MSL is different from simple obesity, which is characterized by the presence of well-distributed total body fat. In patients affected by MSL symmetric, nonencapsulated fat masses are present in the face, neck, occipital region, and supraclavicular fossa. Fat deposits around the cervical region form a “buffalo hump” and a “horse collar,” while, fat deposits around the parotid region may appear as “hamster cheek.” Fat can penetrate deeply in the surrounding tissues, involving vessels, nerves, and muscles and compressing trachea and esophagus.The etiology is unknown although autosomal dominant or mitochondrial inheritance has been postulated. However, the great majority of cases of MSL occur in men aged between 30 and 70 years with known alcoholism (in 60/90% of cases). The disorder predominantly affects white males  of Mediterranean and eastern European populations .The diagnosis is usually easily made on the basis of the history, and clinical appearance. CT or MRI imaging further confirm the diagnosis and value the deeper fatty tissue distribution.A 65-year-old man presented to our department complaining severe dyspnea and with an 8-year history of a slowly growing fatty mass in the neck, trunk, and upper parts of the arms. The patient began to have difficulty breathing for the last two weeks according to the gradual growth of the mass. The patient had a history of heavy alcohol consumption, altered lipid metabolism, and was a nonsmoker. Laryngoscopic examination revealed fatty infiltration of the left preepiglottic and parapharyngeal space with reduction of the lumen of the laryngeal vestibule determining dyspnea . Compute A 55-year-old man presented with progressively enlarged masses around his neck for more than 7 years. He had a 25-year history of alcohol abuse. Laboratory examination showed elevated transaminases. Physical examination showed multiple soft masses involving the neck, occipital region, suprasternal, and supraclavear fossa . CT scan A 58-year-old man presented with a 5-year history of a painless, soft, and slow-growing swelling of the neck, upper trunk, upper back, and shoulders . The patTwo different types of lipomatosis have been identified: familial multiple lipomatosis (FML) and multiple symmetric lipomatosis (MSL). FML is characterized by discrete lipomas that interest the extremities and generally are absent from the neck and shoulders. MSL is a rare disorder marked by the presence of multiple, symmetric nonencapsulated fat masses in the face, neck, upper trunk, and occasionally other areas. Frequently associated findings include hyperlipidemia, hyperuricemia, gout, diabetes mellitus, hypertension, hypothyroidism, liver disease, and polyneuropathies.The pathogenesis of Madelung's disease is still unknown. Nevertheless, several hypothesis such as defect in the adrenergic stimulated lipolysis, a primary defect within the surface membrane of the adipocyte cell, or a defect in brown mitochondrial DNA (both in inherited and acquired defect) have been proposed , 6.The clinical course of MSL is characterized by a rapid progressing growth of the fat deposits during the early phases of the disease, which thereafter either slowly progresses or remains stable for many years. The long-term lipomatous deposits are often large and cosmetically deforming, furthermore they can cause compression of the upper aerodigestive tract and of great veins. Consequently the patient may complain of dyspnea, dysphagia, and venous stasis in advanced cases –10. MaliAlcohol withdrawal and weight reduction are recommended, although they cannot reverse or stop the course of disease. Medical treatment is not effective. Liposuction was proposed as MSL treatment in patients with smaller masses . SurgicaThe cases, described above, characterize three manifestations of the disease. The first one, beside cosmetic appearance, complained of involvement of the left-superior mediastinum and the laryngotracheal region with compression and dislocation of larynx and superior part of trachea. Fat tissue penetrated in larynx reducing the supraglottic space and provoking inspiratory dyspnea. Up till now, only 7 documented cases of direct laryngeal involvement by proliferating adipose tissue in MSL were reported in literature. All the authors proposed the same treatment: a surgical lipectomy in order to decompress the laryngotracheal region and a microsuspension direct laryngoscopic approach to remove the obstructive laryngeal mass , 10.The second patient complained about his cosmetic aspect and was in trouble finding clothes fitting his neck. Because of aesthetic, psychological, and social reasons the patient was submitted to surgical treatment. Abstinence from alcohol was recommended to decrease the rate of recurrence.The third subject presented the typical picture of the disease with thickened soft tissue in anterior neck, nape, and upper trunk. In this case, there was no history of heavy alcohol consumption, signs of altered lipid metabolism, or other metabolic disorders. The surgery was planned in order to reduce the size of lipomatous masses and patient's inability to move neck and arms freely. In the treatment of our patients we did not consider liposuction because of the extension of fatty deposits. Moreover, lipectomy by open surgery is recommended for proper identification of major vessels and nerves and offers the chance of more extensive debulking.


Drug-related hepatotoxicity is a common medical problem with implications for health systems. It constitutes a cause of acute liver failure and, in many cases, is responsible for the rejection of new pharmacological agents during efficacy and safety studies. Risk factors, as well as pathogenesis of drug-induced liver injury, are poorly understood. The diagnosis of drug-induced liver injury is challenging; it is difficult to define the cause of drug hepatotoxicity due to the heterogeneity of the clinical presentation and the absence of established criteria for accurate and reproducible identification of drug-associated liver toxicity.We report the case of a 25-year-old Hispanic woman admitted to our Clinical Hepatology Unit with symptoms of acute hepatitis of unknown etiology. She was diagnosed with albendazole-induced granulomatous hepatitis after ruling out other possible causes, based on laboratory studies, liver biopsy, medical history, detailed drug history, and spontaneous improvement of her liver biochemical profile after medication withdrawal. This diagnosis was supported by the Council for International Organizations of Medical Sciences-Roussel Uclaf Causality Assessment Method, which showed a likely correlation between hepatocellular damage and drug toxicity as the etiology.Our patient’s suspected diagnosis was albendazole-induced granulomatous hepatitis with confirmatory histologic pattern. This case deserves particular attention due to the wide use of albendazole in our country (Colombia) and the prevalent medical issue of drug-related hepatotoxicity. Granulomatous hepatitis is a difficult disease to diagnose. The etiology of these lesions is rarely determined histologically, and the presence of granulomas in the liver does not necessarily imply a granulomatous process. The lesion pattern is a granulomatous inflammatory reaction with the formation of chronic granulomas, composed of aggregates of cells, epithelioid macrophages arranged in a collar surrounded by mononuclear cells and occasional plasma cells. The etiology is usually infectious , but may also develop in autoimmune disease, such as primary biliary cirrhosis and rheumatic fever, as well as having an unknown origin, such as sarcoidosis, or foreign body reaction in response to drug-induced toxicity ,2.In order for a drug to be responsible for granulomatous hepatitis and make a definitive diagnosis of drug-induced liver injury (DILI), it is necessary to exclude other causes and demonstrate the improvement of the condition after stopping the offending drug . HistoloPatients usually present with symptoms such as fever, arthralgia, nausea, and vomiting in the month following drug initiation, although the symptoms may be delayed. Physical examination shows the presence of jaundice and hepatomegaly. Liver function tests show abnormalities of transaminases and alkaline phosphatase. The presence of hyperbilirubinemia and peripheral blood eosinophilia are not seen in all patients but, when present, suggest drug-induced hepatitis .There are no absolute criteria or specific method for the diagnosis of toxic hepatitis. The most widely used scale is the Council for International Organizations of Medical Sciences (CIOMS)-Roussel Uclaf Causality Assessment Method (RUCAM), developed in 1995, which relates a causative agent and toxic liver damage, and has the following results: “highly probable”, “probable”, “possible”, “unlikely”, or “excluded”, according to the total score. This method has proven to be more accurate and reproducible compared with other methods published in the literature -6.Ascaris lumbricoides and other helminth infections, sometimes without medical prescription in our country (Colombia). In the literature, there are few reports of granulomatous hepatitis associated with this group of drugs.This article describes the case of a patient with albendazole-induced granulomatous hepatitis with confirmatory histologic pattern. This case deserves special attention due to the wide use of albendazole for the treatment of This case report describes a 25-year-old Hispanic woman, without significant past medical history, who presented with progressive jaundice, associated with right upper quadrant pain, fatigue, weakness, dark urine, without acholia, fever, or vomiting. On physical examination, the patient had icteric sclerae, no hepatomegaly and no stigmata of chronic liver disease. The laboratory results are shown in Table With the clinical and laboratory diagnosis, a preliminary diagnostic approach to acute hepatitis of unclarified etiology was established. We performed a percutaneous liver biopsy guided by ultrasound, which showed portal inflammatory infiltrate of lymphocytes, plasma cells and neutrophils, with necrosis of the hepatocytes of the limiting plate, and macrophage infiltrate composed of epithelioid granulomas, forming a non-necrotizing aspect in the hepatic sinusoids Figures  and 2. SThe self-limiting condition, as well as the gradual normalization in her liver profile, supported the possibility of toxic hepatitis. Patient monitoring without any intervention was decided. Table Drug-related hepatotoxicity is a common medical problem, with implications for health systems, and is also a cause of acute liver failure and, in many cases, responsible for the elimination of new pharmacological agents during efficacy and safety studies. Risk factors and pathogenesis of DILI are poorly understood. The diagnosis of DILI is one of exclusion, because it is not easy to define a toxic etiology as the cause of liver disease due to the heterogeneity of the clinical presentation and evolution. It can range from transient elevations in liver enzymes to liver failure and even symptomatic chronic liver disease ,7.Studies indicate that antibiotics, agents with central nervous system action, herbal supplements, and immunomodulatory agents are the most common cause of DILI in the United States of America. Hepatocellular injury patterns are more common in younger patients, whereas patterns of cholestasis prevail in older patients ,5,7. TheThe Naranjo Probability Scale and Clinical Diagnostic Scale are also used to assess the causality of drug-induced hepatotoxicity . The CIOIn clinical trials, treatment with albendazole has been associated with mild to moderate elevations of liver enzymes in about 16% of patients. Although generally returned to normal after discontinuation of treatment, there have been reports of persistent hepatitis .Ascaris in the presence of fever, diarrhea, and eosinophilia. Liver biopsy results were consistent with the diagnosis of granulomatous hepatitis [At the time of this review, only three articles were indexed in MEDLINE: the first describes a case of granulomatous hepatitis induced by mebendazole administration in a patient with cytolytic hepatitis with eosinophilia to treat infestation epatitis . Anotherepatitis . The diaepatitis . The excThe third case reported acute hepatitis with jaundice and slightly elevated liver function tests in a 7-year-old patient after administration of oral albendazole . This siCompared to the case presented in the reports mentioned above, the diagnosis in these reports was conducted by history of ingestion of an antiparasitic agent and the presence of eosinophilia, the difference with the case presented relied on the presence of fever and the period of time until symptoms developed.The liver abnormalities are classified into three types: hepatocellular, cholestatic, and combined, according to the levels of liver enzymes . In the In many countries, the health system must be advised of the importance of controlling the sale of “over-the-counter” drugs, including antibiotics, in order to avoid unnecessary hepatotoxicity.This case illustrates how albendazole-induced granulomatous hepatitis, although rare, should be considered in patients in whom other causes have been excluded, thus presenting resolution of symptoms after medication withdrawal. The initial clinical presentation of this patient, laboratory findings, previous use of albendazole, and self-limiting condition with a gradual normalization of liver profile after removal of the drug, supported the possibility of toxic hepatitis. The diagnosis of DILI is one of exclusion, because it is not easy to define a toxic etiology as the cause of liver disease due to the heterogeneity of the clinical presentation and evolution. The CIOMS-RUCAM scale showed a “possible” relationship with a score of five, which supported the diagnosis of albendazole-induced granulomatous hepatitis with a pattern of hepatocellular damage. This case deserves special attention due to the wide use of albendazole in our country and because drug-related hepatotoxicity is a frequent medical problem.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.The authors declare that they have no conflicts of interest.JIM, AEM, and JCR analyzed and interpreted the patient’s data regarding liver studies. JCP analyzed and interpreted the patient data regarding the performed liver studies and liver histology. All authors wrote, read, and approved the final manuscript.


Hyperglycemia and its associated biochemical abnormalities damage vascular wall cells, especially the endothelium, leading to an increased risk of cardiovascular events and disease, as well as microangiopathy and end-organ complications. In the last decade, accumulating data suggest that vascular repair mechanisms are important to maintain normal homeostasis of the arterial wall and to prevent development of pathologic processes, such as atherosclerosis, restenosis, and microvascular disease. Diabetes mellitus, through the impairment of vascular stem and progenitor cells, entails a defective repair of the injured endothelium. The biochemical and cellular mechanisms that account for reduced or functionally impaired vascular progenitor cells in diabetes are not fully elucidated, and this is an intense area of research. Additionally, therapeutic approaches to modulate the endogenous reparative/regenerative processes are of particular interest in the setting of experimental and clinical diabetes research.For this special issue of Experimental Diabetes Research, we invited investigators to contribute with original research articles and review articles that stimulate the continuing efforts to understand the molecular and cellular aspects underlying defective vascular repair by means of stem/progenitor cells in diabetes, as well as the development of interventions to reverse it. The journal has received a variety of valuable submissions spanning the pathophysiological and therapeutic implications of vascular stem/progenitor cells.The pathophysiological implications are herein described in the setting of both diabetes and the metabolic syndrome. S. Devaraj and I. Jialal report how number and/or functionality of endothelial progenitor cells (EPCs) could emerge as a novel cellular biomarker of endothelial/vascular dysfunction and cardiovascular disease (CVD) risk in patients with the metabolic syndrome. In the setting of diabetes, a focus review highlights the central contribution played by bone-marrow-derived progenitor cells in the development and progression of chronic complications. Not only are EPCs reduced and dysfunctional in diabetes, but they also appear to have a deranged differentiation capacity, which is shifted toward a procalcific phenotype that may have a negative impact on ectopic calcification and atherosclerosis. Of note, circulating progenitor cell phenotypes are not limited to EPC, but may include a variety of lineage-committed cells relevant for the pathobiology of diabetic complications. As an example, the level of pericyte progenitor cells (PPCs) in type 2 diabetes appears to be related to microangiopathy in response to glucose-lowering therapy. Among disparate complications, retinopathy has received a special attention: while G. Tremolada and colleagues provide a comprehensive analysis of the mechanisms of neoangiogenesis in the diabetic retina, R. Longeras et al. show how pigment-epithelium-derived-factor- (PEDF-) 34 attenuates EPC mobilization from the bone marrow into the bloodstream during retinal neovascularization. This therapeutic approach can now be considered part of the armamentarium available to reverse microangiopathy, through regenerative cells. In parallel, S. Bernardi et al. provided an analysis of cell-based strategies to counter diabetic complications that have been so far devised and applied in the experimental and clinical settings. Besides cell therapies, several other pharmacologic and nonpharmacologic approaches have shown ability to reverse EPCs dysfunction in diabetes.In conclusion, this special issue provides a series of updated reviews on vascular stem/progenitor cell defects in diabetes and on the therapeutic approaches to reverse them and counter diabetic complications. Original contributions help us to dissect the complexity of vascular stem/progenitor cell biology and trace the way for future studies in this field. Amazingly, circulating progenitor cells are uncovering an entirely new scenario in diabetology research: it is all in the blood!Gian Paolo FadiniGian Paolo FadiniPaolo MadedduPaolo MadedduJohannes WaltenbergerJohannes WaltenbergerPaolo FiorinaPaolo Fiorina


The association between osteoporosis and jawbones remains an argument of debate. Both osteoporosis and periodontal diseases are bone resorptive diseases; it has been hypothesized that osteoporosis could be a risk factor for the progression of periodontal disease and vice versa. Hypothetical models linking the two conditions exist: in particular, it is supposed that the osteoporosis-related bone mass density reduction may accelerate alveolar bone resorption caused by periodontitis, resulting in a facilitated periodontal bacteria invasion. Invading bacteria, in turn, may alter the normal homeostasis of bone tissue, increasing osteoclastic activity and reducing local and systemic bone density by both direct effects (release of toxins) and/or indirect mechanisms (release of inflammatory mediators). Current evidence provides conflicting results due to potential biases related to study design, samples size and endpoints. The aim of this article is to review and summarize the published literature on the associations between osteoporosis and different oral conditions such as bone loss in the jaws, periodontal diseases, and tooth loss.Further well-controlled studies are needed to better elucidate the inter-relationship between systemic and oral bone loss and to clarify whether dentists could usefully provide early warning for osteoporosis risk. Key words:Osteoporosis, periodontitis, oral bone loss, tooth loss, edentulism, bone mineral density. Osteoporosis (OP) is a systemic skeletal disease characterized by low bone mass and micro architectural deterioration of bone tissue, with a consequent increase in fragility and susceptibility to fracture of bones. In the past, OP was considered a physiological process associated with ageing, but today it is recognized as a multifactorial chronic systemic disease. OP may affect also the jawbones, whose structure may be impaired by other conditions resulting in bone loss. One of these, is periodontitis (PD), a chronic infection-mediated condition modulated by different genetic and environmental factors, characterized, in advanced forms, by loss of the soft tissue attachment to teeth and resorption of alveolar bone . PD is the prototype of a low grade local infection  associated with local  immune-inflammatory response causing periodontal tissue damages/destruction and a mild individual systemic inflammatory response contributing to the global inflammatory burden and to its related dangerous effects. PD is very prevalent in the general population in the same age range affected by OP. In fact, moderate and advanced periodontitis affects, respectively, approximately 30% and 10% of the adult populations of United States. Deep periodontal pockets  are present in 2-18% of adults in western countries and at higher prevalence in developing countries , and hypothetical models exist linking OP and PD . It is wThe authors performed a literature review in MEDLINE/ PubMed and Cochrane Oral Health Group`s Trial Register by the main key words related . In this paper we are going to review further evidence regarding the potential correlation between OP and PD.-Osteoporosis and The JawbonesOP can affect several skeletal sites including jawbones. Nonetheless, jawbones have some peculiar features related to the type of ossification and the high turnover induced by masticator mechanical stresses. Morphological studies have shown that the cortical bone porosity of the upper jaw increases with age; in addition, a considerable variation of the thickness and cortical porosity exists in different areas of the mandible  in relation to sex, with significantly higher values in males than females. The body of the mandible and the posterior alveolar processes, consisting predominantly of cortical bone, are very similar to the diaphysis of long bones, while in the anterior alveolar processes of the mandible and in the alveolar processes of the jaw, bone architecture is mostly trabecular. According to some authors the rate of bone turnover at the level of alveolar processes would be greater than in long bones, so the loss of bone mass could manifest earlier at the alveolus than at other skeletal segments, thus, representing an early indicator of OP. These observations are consistent with those described by von Wowern et al.  who propIn addition, whenever teeth are lost the resorption of alveolar residual ridges progressively occurs whether the subject remains edentulous or is rehabilitated with removable prostheses. It has been also found that in patients with osteopenia or OP the porosity observed in the jaws (atrophy from disuse) increases, and that the improvement in chewing produced by prosthetic rehabilitation reduces the amount of bone resorption.The correlation between changes in systemic BMD and the jawbones, has been assessed by Dual Photon Absorptiometry (DPA) Dual Energy X-ray Absorptiometry (DEXA) and Quantitative Computed Tomography (QCT) -5, suita-Periodontitis and OsteoporosisPD is a complex disease entity with a multifactorial etiology in which the inflammatory response of the periodontal tissue to bacterial infection ends up with periodontal ligament detachment from the cement, formation of periodontal pockets, alveolar bone resorption, gingival recession, tooth mobility/migration.Periodontitis is the major cause of alveolar bone resorption and tooth attachment loss resulting in tooth loss and, consequently, additional bone resorption. It is influenced by environmental factors as well as by genetic factors; thus, periodontal diagnosis requires oral/periodontal and assessment that`s to say: 1) patient`s medical and dental histories; 2) presence of clinical signs of inflammation of gingival tissues, including bleeding on probing; 3) pro-bing depths; 4); extent and pattern of attachment loss and bone defects 5) presence of various signs and symptoms, including pain, tooth mobility and amount of the observable plaque and calculus -7. ObtaiThe first reports on the possible association between systemic osteoporotic bone loss and local oral bone loss were released back in the`60s by Groen et al.  who sugga) clinical attachment level (CAL), depth of the periodontal pocket (PPD).b) alveolar crest height (ACH) or height of the residual alveolar bone (ABH).c) tooth loss (TL).The most significant published works for each of them are detailed , Table 4OP may affect jawbones and the resulting modifications visible at the routine radiological examination  may be useful for OP early diagnosis. In addition, these modifications might potentially speed up periodontal tissues breakdown caused by PD . Under tOn the other hand, besides the presence of common risk factors, a possible interplay between OP and PD is also suggested at a pathogenetic level. In fact, a bi-directional interference between PD and OP has been proposed: in particular, the reduced BMD, characterizing OP and the related alteration of trabecular pattern may lead to a more rapid jawbones resorption caused by PD, resulting in the invasion of periodontal bacteria -9. InvadThus, a relationship between OP and PD might be probable, but further prospective and sensitive studies are required in order to provide definitive evidence.By now, available data underline the primary importance of dentists in the early diagnosis of OP, because of the opportunity to assess the health of the entire skeleton of the patient through dental radiography. This is of considerable clinical interest, considering that such dental radiological investigations are routinely performed for diagnosis and treatment of dental and periodontal diseases, which are particularly frequent in the same population affected by OP. This may also provide clues for new preventive strategies and/or early therapeutic approach resulting in a potential reduction of bone resorption and contributing to maintain bone biomechanical characteristics .In fact, the prevention of OP is the most rational and modern approach to defeat the disease , and ear


Larval zebrafish possess several experimental advantages for investigating the molecular and neural bases of learning and memory. Despite this, neuroscientists have only recently begun to use these animals to study memory. However, in a relatively short period of time a number of forms of learning have been described in zebrafish larvae, and significant progress has been made toward their understanding. Here we provide a comprehensive review of this progress; we also describe several promising new experimental technologies currently being used in larval zebrafish that are likely to contribute major insights into the processes that underlie learning and memory. Danio rerio. Zebrafish display a rich repertoire of behaviors, including associative learning , together with the general experimental advantages of zebrafish for reductionist analyses of behavior possessing different ontogenies Figure , might bHabituation is a non-associative form of learning during which the response of an animal to repeated presentations of a stimulus of fixed intensity or strength gradually declines; furthermore, this decline is not due to sensory adaptation, motor fati, or injury  activity, whereas rapid habituation does not. Wolman et al. (dl-2-amino-5-phosphonopentanoic acid (APV), a competitive NMDAR antagonist used in the experiments of Roberts et al., did not alter rapid habituation). Recently, we  larval zebrafish show another form of escape behavior that differs from the C-start; this response, the O-bend, is characterized by a significantly larger amplitude bend of the fish's body than occurs during the C-start  has been observed by three laboratories. After habituating the escape response in larvae to auditory pips, Best et al.  producedAplysia, which results from modulatory actions on sensorimotor pathways within the snail of another monoamine, serotonin; serotonin's release, in turn, is triggered by noxious stimulation  has also recently been shown in larval zebrafish. Mu et al.  used audThe enhancing action of the flash on the sound-elicited C-start in zebrafish larvae appears to be quite brief. It remains to be determined whether more persistent enhancement could be induced in the larvae. Possibly, the briefness of the flash-induced modulation of the escape response may reflects the developmental immaturity of monoaminergic neurotransmission within the CNS of larval fish. In support of this idea, Buske and Gerlai  report tDrug-induced sensitization of locomotor activity has been shown in both larval   of an animal's voluntary response to a reinforcing stimulus alters the future probability of the animal's responses or behavior; in classical conditioning the animal's (involuntary) responses to the training stimuli are not altered by the behavior's outcomes . The fish were tested for social preference when they reached adulthood (≥90 dpf). Social isolates exhibited no preference for either the wild-type or nacre phenotypes. However, fish in the other groups preferred the phenotypes they had been raised with, e.g., wild-type fish raised with nacre fish from hatching preferred to shoal with nacre fish as adults. These results suggest that shoaling preferences are determined, at least partly, by early experience. In a later study  It is believed that this social behavior serves, in part, as a protection against predation through increasing the detection of predators and decreasing the probability of individual capture Peichel, . As firsTwo papers by Gerlai and colleagues provide some additional support for the notion that shoaling is a learned social behavior in zebrafish. Al-Imari and Gerlai  raised zAs the above review indicates, zebrafish larvae possess a surprisingly rich repertoire of learning abilities, including not only non-associative, but also associative and even social learning. Given that at present neurobiologists lack a comprehensive understanding of any form of learning in any organism , and then the DNA of these fish is screened and sequenced to identify mutations within specific genes . This resource should lead to the identification of novel molecular pathways involved in learning and memory. In addition, newer techniques, such as zinc finger nucleases, CRISPR, and TALENS, allow for site-directed mutagenesis of zebrafish genes (Doyon et al., Drosophila memory (Joiner and Griffith, In addition to the development of new learning and memory assays in larval zebrafish, one can anticipate that the genetic tools available for use in zebrafish will steadily improve (see Figure Investigators have long taken advantage of the transparency of larvae to image optical activity in the brain of intact zebrafish using calcium indicator dyes (Fetcho and O'Malley, Another new optical method to which zebrafish larvae are highly amenable is optogenetics. Through the use of light-gated glutamate receptors (Szobota et al., Mention should also be made of other new methods for manipulating or monitoring neural function in the intact larval zebrafish's brain. For example, GAL4-UAS technology can be used to target the expression of tetanus toxin, which blocks neurotransmitter release, to specific neurons and thereby eliminate their contribution to behavior-related brain activity (Asakawa et al., Zebrafish larvae are uniquely adapted to new genetic and optical technologies for studies of behavior. For this reason, it is gratifying that these relatively simple animals possess significant capabilities for learning. In particular, as we have discussed in this review, zebrafish larvae exhibit not only short-term, but also long-term memory, as well as associative and social learning. As neurobiologists increasingly recognize the advantages of zebrafish larvae for investigations of learning and memory, our knowledge of the mnemonic repertoire of these animals will undoubtedly expand. Possibly, studies of this tiny, immature, deceptively humble creature will one day unlock some of the most profound secrets about how brains acquire and store memories.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In this book a group of independed-minded academics has orchestrated a multi-authored text that represents an update of knowledge concerning how motivation influences Cardiovascular (CV) response.Discussing diverse motivational approaches that are representative of works carried out in several areas of psychology, health implications of the linkages between motivational variables and CV response have been investigated.The volume is divided into two major parts: Part I includes chapters that concern mechanisms of motivational influence on CV response, while in the Part II motivational paths to carry out with the aim of investigate CV response in different life circumstances have been considered.In more detail, 4 subsections organize Part I through 10 chapters, and 3 subsections constitute Part II by means of 9 chapters, each of those preceded by a summary of the key points.The opening chapters discuss the importance of modern neuroimaging techniques in allowing occasions to investigate how the interplay between CV status, cognitive-emotional functioning, and environmental demands are realized within the central and peripheral nervous systems.The relationship between emotional arousal and CV response has been noteworthy argued and enriched by results from recent research findings in various disciplines (Pietrabissa et al., Part II mainly contains evidences that CV activity is an indicator or even cause for CV diseases development, also including explanations about the role covered by gender, psychological processes, and social interactions in influencing health outcomes via relevant biological pathway. In addition, a set of considerations that may guide future research on this subject are discussed.Due to the various contributions from different authors of different countries, both style of writing and chapters arrangement widely varies.Some issues are effectively revisited on several occasions in the volume, constituting minor imperfections in an otherwise excellent, comprehensive, and up-to-date overview of mechanisms and applications related to CV disease. In fact, this book, edited by two psychologists and written by an International group of specialists in different fields of medicine, successfully covers the subject.Because of diseases generally display a multifactorial aetiology and symptoms require to be assumed as manifestations of a complex interplay of several factors, the bio-psycho-social approach of illness theorized by Engel  remains Overall, this book represents a well-collated collection of research outcomes, successfully demonstrating the importance of both psychological factors and motivation in the treatment of patients suffering from CV diseases (Manzoni et al.,