Books on the topic 'Variant rara'

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder of the heart muscle which is typically inherited in an autosomal dominant manner. It is believed to be familial in over 50% of cases. A recessive mode of inheritance has also been reported in syndromic cases with cardiocutaneous features. The classic form of the disorder is considered to be ‘a disease of the desmosome’ as pathogenic variants have been identified in five genes encoding key desmosomal proteins: plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, and desmocollin-2. Mutations in these genes account for 30–50% of ARVC cases. A further eight non-desmosomal genes have also been implicated in the pathogenesis of the disorder but only account for rare cases. Studies of patients with ARVC-associated gene mutations have revealed marked genetic heterogeneity and very limited genotype–phenotype correlation. Disease expression often varies significantly amongst individuals carrying the same mutation. It has been proposed that the presence of more than one sequence variant is required to determine overt clinical disease and patients with multiple variants have a more severe phenotype compared to single variant carriers. Identification of a potentially pathogenic variant comprises a major criterion in the diagnosis of ARVC but informative integration of genetic testing into clinical practice remains challenging. Gene testing should be used to identify asymptomatic family members at risk and only aids diagnosis in cases of high suspicion for ARVC, along with other evident features of the disease already present. However, genetic findings should be used with caution in clinical practice and their interpretation must be performed in expert centres.

This chapter reviews the evidence suggesting that there is a strong genetic component to ADHD and the efforts to identify the specific genetic factors that might be involved. It discusses the different types of genetic contributions, from common to rare variants, and the evidence that these are involved in the aetiology of the disorder. An overview of the methodological strategies employed, including genome-wide association studies (GWAS), polygenic risk score, and copy number variant (CNV) analyses, is undertaken, as well as discussion of the strengths and pitfalls of such work. The contradictory findings in the field and controversies that arise as a result are also explored. Finally, this chapter considers how the heritability of ADHD and specific genetic factors involved need to be examined in the context of clinical factors such as comorbidity and how these factors affect investigations into the genetics of ADHD.

Chapter 5 reviews epidemiologic studies conducted to identify germline (inherited) susceptibility loci. These studies can involve associations observed within high-risk family pedigrees or in large studies of unrelated individuals. The chapter reviews the methods used to estimate the aggregate contribution of inherited genetic susceptibility and to identify specific genetic loci associated with risk. Although there is considerable variability across cancers, most cancers exhibit familial clustering, driven in part by a small number of known rare variants with large relative risks and a larger number of common variants with modest relative risks. The chapter discusses the implications of these findings for clinical care, public health, and tumor biology. It closes with a discussion of open questions, most notably the puzzle of “missing heritability”: the fact that—despite tremendous advances—multiple lines of evidence suggest that most specific risk variants, both rare and common, have yet to be discovered.

Clinical features 354Management 355Liver disease in other forms of α‎1-AT deficiency 355α‎1-Antitrypsin (α‎1-AT) is a 55 kD glycoprotein produced predominantly by hepatocytes, alveolar macrophages and intestinal endothelial cells. It acts as a protease inhibitor during an acute-phase response. It can be electrophoretically differentiated into four main variants: PiM (normal), PiZ, PiS, and Pi Null (abnormal). There are >80 other rare, clinically irrelevant, variants. ...

Schizophrenia and bipolar disorder are the classic psychotic disorders. Both diseases are strongly familial, but have proven recalcitrant to genetic methodologies for identifying the etiology until recently. There is now convincing genetic evidence that indicates a contribution of many DNA changes to the risk of becoming ill. For schizophrenia, there are large contributions of rare copy number variants and common single nucleotide variants, with an overall highly polygenic genetic architecture. For bipolar disorder, the role of copy number variation appears to be much less pronounced. Specific common single nucleotide polymorphisms are associated, and there is evidence for polygenicity. Several surprises have emerged from the genetic data that indicate there is significantly more molecular overlap in copy number variants between autism and schizophrenia, and in common variants between schizophrenia and bipolar disorder.

Congenital heart disease (CHD) is defined as a structural cardiac malformation resulting from an abnormality of development; 8% of CHD is inherited in a Mendelian fashion and 12% results from chromosomal imbalance. Recurrence risk and new research suggest that even the remaining 80% of patients without an identifiable familial or syndromic basis for disease may have an identifiable genetic cause. The potential to understand these mechanisms is increasing with the advent of new sequencing techniques which have identified multiple or single rare variants and/or copy number variants clustering in cardiac developmental genes as well as common variants that may also contribute to disease, for example by altering metabolic pathways. Work in model organisms such as mouse and zebrafish has been pivotal in identifying CHD candidate genes. Future challenges involve translating the discoveries made in mouse models to human CHD genetics and manipulating potentially protective pathways to prevent disease.

It has long been known that the human genome is subject to deletion and duplication of genetic material by various molecular mechanisms. Until recently, such events were assumed to be relatively rare phenomena. It is now known that submicroscopic deletions or duplications calledcopy number variants(CNVs) are a major source of genomic variation. Rare CNVs (defined as occurring in less than 1 percent of the population) have been implicated in schizophrenia and autism. Measured in terms of odds ratios, individual CNVs have been shown to have large effects, some increasing the risk of disorder several-fold. But they are incompletely penetrant, no one CNV is either necessary or sufficient to cause the disorder. The findings are less clear-cut with bipolar disorder but, here, too, rare CNVs probably play a role. In unipolar depression, initial evidence suggests an overall increase in rare CNVs that disrupt exons, the coding regions of genes.

Fabry disease was initially believed to be a very rare disorder, but an increase in prevalence following screening studies revealed that it may be more frequent in a less severe (nonclassical) variant. The adult physician can encounter both phenotypes: classical disease arising in childhood, or after establishing the diagnosis in an adult male. The nonclassical phenotype is usually diagnosed after additional investigations in a patient with renal disease or left ventricular hypertrophy (LVH) of unknown origin. Enzyme replacement therapy (ERT) appears to have a modest effect in Fabry disease, and many challenges remain both in understanding the pathophysiology and natural history as well as in improving patient outcomes.

Synaesthesia is often described as a rare neurological condition where one sense appears to merge or cross with another. It is a multi-variant condition that can present itself in many different ways: some synaesthetes taste words, while others see colours when they hear sounds. Synaesthesia: A Very Short Introduction describes this extraordinary condition, explaining what synaesthesia is, how it manifests itself, what causes it, how it feels, how it links to creativity and the arts, and what it can tell us about every human’s perceptions of reality. Delving into the neuroscience behind synaesthesia, it also relates contemporary attempts at understanding both the genetic causes of synaesthesia, and how synesthetic sensations occur in the brain.

New nipple retraction and new nipple inversion can be secondary to malignancy, post-surgical change, inflammation, or infection. Paget disease of the nipple is characterized by an inflammatory response of the nipple epidermis to malignant cells extending from ductal carcinoma in the lactiferous sinus. A mass arising within the nipple is rare and usually a variant of a papilloma arising in the nipple (nipple adenoma). This chapter, appearing in the section on nipple, skin, and lymph nodes, reviews the key clinical features, associated imaging findings, imaging protocols and pitfalls, differential diagnoses, and management recommendations for patients presenting with nipple retraction. Topics discussed include imaging features of nipple retraction, both benign and malignant causes of nipple retraction, Paget disease of the nipple, and masses occurring in the nipple.

La medicina interna representa una especialidad de mucho valor y responsabilidad social, la misma cumple un importante papel en el progreso de la ciencia y el arte médico; no obstante, en las últimas décadas se ha observado como esta profesión médica y sus sub especialidades han vivido numerosos cambios, los cuales, en su efecto, se deben a la entrada vertiginosa de recursos tecnológicos y la forma en que los médicos han adaptado estos recursos al quehacer profesional. Efectivamente, el especialista de la medicina interna representa un profesional de gran valor en los cuidados de todas aquellas enfermedades de orden crónico, los mismos, fueron como se ha señalado anteriormente, fundadores de las sociedades de sub especialistas de esta rama, creando ramas de cuidado médico como lo son: la Cardiología, Gastroenterología, Hematología, Reumatología, Nefrología, Infectología, Endocrinología, Diabetología, siendo sus discípulos, los que perfeccionaron e impulsaron las más nuevas, como la Medicina Intensiva y la Geriatría. De manera satisfactoria por haber culminado este material informativo, se plantea la importancia que tiene la elaboración del presente libro, a través del mismo se pretende brindar al público lector y especialistas de la medicina en general, una visión variada sobre los aspectos que comprende esta rama médica y algunas de las patologías a las que se enfrentan durante su ejercicio profesional, sobre todo, aquellas que son de mayor incidencia y representan un problema de salud pública, considerando que son los profesionales internistas, los expertos, a quienes recurren los médicos de atención primaria y el resto de las ramas médicas, cuando precisan atender a enfermos complejos cuyo diagnóstico es difícil, o se encuentran afectados por varias enfermedades haciendo que su diagnóstico clínico sea confuso.

‘Tumours of the haematopoietic system’ examines the epidemiology, the pathogenesis, and the clinical features of adult and childhood primary central nervous system lymphomas (PCNSLs), extranodal forms of non-Hodgkin lymphoma, as well as the histiocytoses included in the World Health Organization (WHO) classification of central nervous system (CNS) tumours. It reviews these features in the most common PCNSL, primary central nervous system diffuse large B-cell lymphoma, as well as the other rare histopathological PCNSL variants including lymphomatoid granulomatosis, T-cell lymphoma, anaplastic large T-cell lymphoma, natural killer/T-cell lymphoma, low-grade lymphoma, mucosa-associated lymphoid tissue (MALT) of the dura, and Hodgkin lymphoma. The chapter also discusses clinical and anatomical PCNSL variants including vitreoretinal lymphoma, leptomeningeal lymphoma, intramedullary spinal cord lymphoma, intravascular lymphoma, and PCNSL in the immunocompromised host. It also reviews the CNS presentations of Langerhans cell histiocytosis and the following non-Langerhans cell histiocytoses: Erdheim–Chester disease, Rosai–Dorfman disease, juvenile xanthogranuloma, and histiocytic sarcoma. It is written for specialists and non-specialists managing these various conditions.

Cerebellar astrocytoma of childhood most commonly refers to cerebellar pilocytic astrocytoma, a World health Organization (WHO) Grade I tumor. However, on occasion cerebellar astrocytomas may demonstrate more aggressive histology including fibrillary astrocytomas, pilomyxoid astrocytomas, and rarely malignant lesions. In the near future, the diagnosis of cerebellar astrocytomas will be simplified by molecular analysis for BRAF fusions rather than a purely morphological approach. The emergence of next-generation sequencing can be expected to identify single nucleotide variations and further expand our understanding of both pilocytic astrocytomas as well as rare variants that occur in the cerebellum. Therapies targeting BRAF (B-raf protooncogene) are currently in clinical trial for adult malignancies and will eventually reach the pediatric population, allowing a targeted approach to recurrent and surgically inaccessible cases of pilocytic astrocytomas.

The distinctive global incidence patterns and risk factors for nasopharyngeal carcinoma (NPC) make this a unique malignancy that represents an epidemiologic challenge. NPC is rare throughout most of the world but relatively common in southern China, Southeast Asia, the Arctic, North Africa, and the Middle East. This pattern is determined in part by the geographic and ethnic distribution of established risk factors for NPC, which include early/aberrant Epstein Barr virus infection, Chinese-style salted fish consumption, family history, certain human leukocyte antigen alleles, and tobacco smoking. Other possible NPC risk factors include certain dietary, occupational, and infectious exposures and genetic variants. Risk factors for NPC in low-incidence regions, where tumors are more often of squamous cell histology than in high-incidence regions, are poorly understood, as are etiologic interactions among genetic, environmental, and infectious risk factors for NPC.

This chapter introduces a new, two-dimensional way of measuring intra-party democracy (IPD). It is argued that assembly-based IPD and plebiscitary IPD are two theoretically different modes of intra-party decision-making. Assembly-based IPD means that discussion and decision over a certain topic takes place at the same time. Plebiscitary IPD disconnects the act of voting from the discussion over the alternatives that are put to a vote. In addition, some parties have opened up plebiscitary decision-making to non-members which is captured by the concept of open plebiscitary IPD. Based on the Political Party Database Project (PPDB) dataset, indices are developed for the three variants of IPD. The empirical analyses here show that assembly-based and plebiscitary IPD are combined by political parties in different ways while open party plebiscites are currently a rare exception.

Attention deficit hyperactivity disorder (ADHD) is a prevalent, early-onset and persistent disorder of inattention, hyperactivity, and impulsivity. The mechanisms of action of ADHD medications, neuroimaging studies, and studies of monoamine systems and animal models suggest that dysregulation of catecholaminergic neurotransmission in cerebellar-corticostriatal circuits plays a key role in the pathophysiology of ADHD. The efficacy of ADHD medications likely arises from their differing profile of effects on (a) dopaminergic and noradrenergic systems and (b) the localization of these effects in prefrontal cortex and striatum. ADHD has a very high heritability, and although molecular genetic studies have found no causal common DNA variants yet, they have found strong evidence that rare duplications and deletions are risk factors for ADHD. Environmental risk factors, especially those that impact early neurodevelopment (i.e., exposure to cigarette smoking and alcohol during pregnancy), also influence susceptibility to ADHD.

Paget’s disease of bone (PDB) affects up to 1% of people of European origin aged 55 years and above. It is characterized by focal abnormalities of bone remodelling which disrupt normal bone architecture, leading to expansion and reduced mechanical strength of affected bones. This can lead to various complications including deformity, fracture, nerve compression syndromes, and osteoarthritis, although many patients are asymptomatic. Genetic factors play a key role in the pathogenesis of PDB. This seems to be mediated by a combination of rare genetic variants which cause familial forms of the disease and common variants which increase susceptibility to environmental triggers. Environmental factors which have been suggested to predispose to PDB include viral infections, calcium and vitamin D deficiency, and excessive mechanical loading of affected bones. The diagnosis can be made by the characteristic changes seen on radiographs, but isotope bone scans are helpful in defining disease extent. Serum alkaline phosphatase levels can be used as a measure of disease activity. Inhibitors of bone resorption are the mainstay of medical management for PDB and bisphosphonates are regarded as the treatment of choice. Bisphosphonates are highly effective at reducing bone turnover in PDB and have been found to heal osteolytic lesions, and normalize bone histology. Although bisphosphonates can improving bone pain caused by elevated bone turnover, most patients require additional therapy to deal with symptoms associated with disease complications. It is currently unclear whether bisphosphonate therapy is effective at preventing complications of PDB.

Paget's disease of bone (PDB) affects up to 1% of people of European origin aged 55 years and above. It is characterized by focal abnormalities of bone remodelling which disrupt normal bone architecture, leading to expansion and reduced mechanical strength of affected bones. This can lead to various complications including deformity, fracture, nerve compression syndromes, and osteoarthritis, although many patients are asymptomatic. Genetic factors play a key role in the pathogenesis of PDB. This seems to be mediated by a combination of rare genetic variants which cause familial forms of the disease and common variants which increase susceptibility to environmental triggers. Environmental factors which have been suggested to predispose to PDB include viral infections, calcium and vitamin D deficiency, and excessive mechanical loading of affected bones. The diagnosis can be made by the characteristic changes seen on radiographs, but isotope bone scans are helpful in defining disease extent. Serum alkaline phosphatase levels can be used as a measure of disease activity. Inhibitors of bone resorption are the mainstay of medical management for PDB and bisphosphonates are regarded as the treatment of choice. Bisphosphonates are highly effective at reducing bone turnover in PDB and have been found to heal osteolytic lesions, and normalize bone histology. Although bisphosphonates can improving bone pain caused by elevated bone turnover, most patients require additional therapy to deal with symptoms associated with disease complications. It is currently unclear whether bisphosphonate therapy is effective at preventing complications of PDB.

Addictive disorders are moderately to highly heritable, indicating that alleles transmitted from parents are protective, or enhance risk by whatever mechanisms. However, the inheritance of addictive disorders is complex, involving hundreds of genes and variants that are both common and rare, and that vary in effect size and context of action. Genes altering risk for addictions have been identified by pathway and candidate gene studies in humans and model organisms, and genomic approaches including genome-wide association, meiotic linkage, and sequencing. Genes responsible for shared liability to different addictive disorders have been identified, as well as genes that are relatively specific in altering risk of addiction to one agent. An impediment to overarching conclusions is that most of the heritability of addictions is unexplained at the level of gene or functional locus. However, new analytic approaches and tools have created new potentials for resolution of the “missing heritability.”

The advent of genome-wide association studies (GWAS) has been an exciting breakthrough in our understanding of the genetic aetiology of autoimmune diseases. Substantial overlap has been found in susceptibility genes across multiple diseases, from connective tissue diseases and rheumatoid arthritis (RA) to inflammatory bowel disease, coeliac disease, and psoriasis. Major technological advances now permit genotyping of millions of single nucleotide polymorphisms (SNPs). Group analysis of SNPs by haplotypes, aided by completion of the Hapmap project, has improved our ability to pinpoint causal genetic variants. International collaboration to pool large-scale cohorts of patients has enabled GWAS in systemic lupus erythematosus (SLE), systemic sclerosis and Behçet's disease, with studies in progress for ANCA-associated vasculitis. These 'hypothesis-free' studies have revealed many novel disease-associated genes. In both SLE and systemic sclerosis, identified genes map to known pathways including antigen presentation (MHC, TNFSF4), autoreactivity of B and T lymphocytes (BLK, BANK1), type I interferon production (STAT4, IRF5) and the NFκ‎B pathway (TNIP1). In SLE alone, additional genes appear to be involved in dysregulated apoptotic cell clearance (ITGAM, TREX1, C1q, C4) and recognition of immune complexes (FCGR2A, FCGR3B). Future developments include whole-genome sequencing to identify rare variants, and efforts to understand functional consequences of susceptibility genes. Putative environmental triggers for connective tissue diseases include infectious agents, especially Epstein-Barr virus; cigarette smoking; occupational exposure to toxins including silica; and low vitamin D, due to its immunomodulatory effects. Despite numerous studies looking at toxin exposure and connective tissue diseases, conclusive evidence is lacking, due to either rarity of exposure or rarity of disease.

Prostate cancer is the most common solid tumor and the second leading cause of cancer-related mortality in American men. Worldwide, prostate cancer ranks second and fifth as a cause of cancer and cancer deaths, respectively. Despite the international burden of disease due to prostate cancer, its etiology is unclear in most cases. Established risk factors include age, race/ancestry, and family history of the disease. Prostate cancer has a strong heritable component, and genome-wide association studies have identified over 110 common risk-associated genetic variants. Family-based sequencing studies have also found rare mutations (e.g., HOXB13) that contribute to prostate cancer susceptibility. Numerous environmental and lifestyle factors (e.g., obesity, diet) have been examined in relation to prostate cancer incidence, but few modifiable exposures have been consistently associated with risk. Some of the variability in results may be related to etiological heterogeneity, with different causes underlying the development of distinct disease subgroups.

Neuronal and mixed neuronal-glial tumours are rare tumours of the central nervous system that occur more commonly in children. Despite a generally benign course, most tumours cause medically intractable seizures, and have been denominated as ‘long-term epilepsy-associated tumours’. The World Health Organization classification distinguishes nine histological variants: dysplastic gangliocytoma of the cerebellum/Lhermitte–Duclos disease, desmoplastic infantile astrocytoma and ganglioglioma, dysembryoplastic neuroepithelial tumour, gangliocytoma and ganglioglioma, central neurocytoma and extraventricular neurocytoma, cerebellar liponeurocytoma, papillary glioneuronal tumour, rosette-forming glioneuronal tumour of the fourth ventricle, and spinal paraganglioma. Early surgery with complete resection may significantly improve the likelihood of postoperative epilepsy freedom. Conformal radiotherapy can be considered in case of patients with incompletely resected symptomatic tumours, atypical or high-grade tumours, or in the case of multiple recurrences despite resections. The role of chemotherapy in these lesions remains poorly defined, while targeted therapies are now available to impact some molecular alterations.

Huntington’s disease (HD) is a rare inherited neurologic disorder due to a single mutational mechanism in a large gene (HTT). The mutation is an abnormal CAG repeat expansion, which is translated to a polyglutamine stretch in the huntingtin protein. The growing field of repeat expansion disorders benefits greatly from the lessons learned from the role of the CAG repeat expansion in HD and its resulting phenotype–genotype correlations. The molecular diagnosis can be difficult, and there are some pitfalls for accurate sizing of the CAG repeat, especially in juvenile HD and for intermediate alleles. Correlation between CAG length and age of onset accounts for up to 72% of the variance in different populations, but the search for genes modifying age of onset or progression of HD is still ongoing.

Scrapie, bovine spongiform encephalopathy (BSE), Creutzfeldt–Jakob disease (CJD), and related diseases of mink (transmissible mink encephalopathy), mule deer and elk (chronic wasting disease) are the founder members of a group of diseases called the transmissible degenerative (or spongiform) encephalopathies (TSE). These diseases can be transmitted by prions from affected to healthy animals by inoculation or by feeding diseased tissues. Prions are cellular proteins that can transfer metabolic and pathological phenotypes vertically from parent to progeny or horizontally between cells and animals. TSEs are characterised by the accumulation of the prion form of the mammalian prion protein (PrPC) in the central nervous system or peripheral tissues of animals and humans. Mutations of the human PrP gene are linked to rare, familial forms of disease and prion-protein gene polymorphisms in humans and other species are linked to survival time and disease characteristics in affected individuals. Iatrogenic transmission of CJD in man has occurred, and a variant form of CJD (vCJD) is due to cross-species transmission of BSE from cattle to humans. Atypical forms of scrapie and BSE have been identified during large-scale monitoring for TSEs worldwide. This chapter outlines our current understanding of scrapie, BSE, CJD and other TSEs and highlights recent progress in defining the role in disease of the prion protein, PrP.

Fibrillary or immunotactoid nephropathy is a rare deposition disease of unknown cause in which highly organized deposits containing immunoglobulin and complement are found in the glomerular basement membrane and mesangium. These deposits are not amyloid fibrils and do not stain with Congo red. They are usually polyclonal and are not associated with monoclonal paraproteins, or with cryoglobulins or systemic lupus, distinguishing them from other non-amyloid fibrillary glomerulopathies. There is debate about whether there is a useful distinction between distinct fibrillary and rarer immunotactoid variants, the rarer immunotactoid variety being associated with larger, more organized, microtubular fibrils and possibly more commonly associated with malignancy (usually lymphoproliferative). However, clinically the conditions are similar. Patients usually present with heavy proteinuria or nephrotic syndrome. Microscopic haematuria is common and many have reduced glomerular filtration rate at presentation. Fifty per cent reach end-stage renal failure in 3–5 years and there is no convincing evidence that any treatment is effective in altering this outcome. Other organs appear to be affected only rarely (lung, liver). The disease may recur post-transplant but not always and usually more slowly, so does not preclude transplantation.

Manuscript Matters illuminates responses to some of John Donne’s most elusive texts by his contemporary audiences. Since examples of seventeenth-century literary criticism prove somewhat rare and frequently ambiguous, this book emphasizes a critical framework rarely used for exhibiting early readers’ exegeses of literary texts: the complete manuscripts containing them. Many literary manuscripts that include poems by Donne and his contemporaries were compiled during their lifetimes, often by members of their circles. For this reason, and because various early modern poems and prose works satirize topical events and prominent figures in highly coded language, attempting to understand early literary interpretations proves challenging but highly valuable. Compilers, scribes, owners, and other readers—men and women who shared in Donne’s political, religious, and social contexts—offer clues to their literary responses within a range of features related to the construction and subsequent use of the manuscripts. This study’s findings call us to investigate more extensively and systematically how certain early manuscripts were constructed through analysis of such features as scripts, titles, sequence of contents, ascriptions, and variant diction. While such studies can throw light on many early modern texts, exploring artifacts containing Donne’s works proves particularly useful because more of his poetry circulated in manuscript than did that of any other early modern poet. Manuscript Matters engages Donne’s satiric, lyric, and religious poetry, as well as his prose paradoxes and problems—refocusing modern interpretation through an early modern lens.

Various disorders result from genetically determined abnormalities of enzymes, the metabolic consequences of which affect the development or functioning of the nervous system. The range of metabolic disturbances is wide, as is the resultant range of clinical syndromes. Although most occur in children, some can present in adult life, and increasing numbers of affected children survive into adult life. In some, specific treatments are possible or are being developed. The last 20 years has seen a considerable expansion in our understanding of the genetic and metabolic basis for many neurological conditions. Particular clinical presentations of neurometabolic disorders include ataxias, movement disorders, childhood epilepsies, or peripheral neuropathy. Detailed coverage of the entire range of inherited metabolic diseases of the nervous system is available in other texts (Brett 1997; Scriver et al. 2001; Menkes et al. 2005).Treatment is possible for some metabolic diseases. For instance, the devastating neurological effects of phenylketonuria have been recognized for many years. Neonatal screening for this disorder and dietary modification in the developed world has removed phenylketonuria from the list of important causes of serious neurological disability in children. This success has led to new challenges in the management of the adult with phenylketonuria and unexpected and devastating effect of the disorder on the unborn child of an untreated Phenylketonuria mother. More recently Biotinidase deficiency has been recognized as an important and easily treatable cause of serious neurological disease usually presenting with early onset drug resistant seizures. This and some other neurometabolic diseases can be identified on neonatal blood screening although a full range of screening is not yet routine in the United Kingdom. More disorders are likely to be picked up at an earlier asymptomatic stage as the sophistication of screening tests increases (Wilcken et al. 2003; Bodamer et al. 2007).Although individual metabolic disorders are rare, collectively such disorders are relatively common. In reality most clinicians will see an individual condition only rarely in a career. Furthermore, patients with certain rare conditions are often concentrated in specialist referral centres, further reducing the exposure of general and paediatric neurologists to these disorders. A recent study into progressive intellectual and neurological deterioration, PIND, gives some information about the relative frequency and distribution of some childhood neurodegenerative diseases in the United Kingdom (Verity et al. 2000; Devereux et al. 2004). Although primarily designed to identify any childhood cases of variant Creutzfeldt- Jakob disease, the study also provided much information about the distribution of neurometabolic disease in children in the United Kingdom. The commonest five causes of progressive intellectual and neurological deterioration over 5 years were Sanfilippo syndrome, 41 cases, adrenoleukodystrophy, 32 cases, late infantile neuronal ceroid lipofuschinosis, 32 cases, mitochondrial cytopathy, 30 cases, and Rett syndrome, 29 cases. Notably, geographical foci of these disorders were also found and correlate with high rate of consanguinity in some local populations.

Histoplasma was initially described from a lesion in a horse by Rivolta in 1873, who named the organism Cryptococcus farciminosum. In 1905, Samuel Darling noted the presence of intracellular organisms in many tissues, including the lungs, of a patient suspected of succumbing to miliary tuberculosis (Darling 1906). Darling named the organism Histoplasma capsulatum , because it appeared to be an encapsulated protozoan-like organism. In 1912, mycologist Henrique da Rocha-Lima reviewed Darling’s slides and noted the cytological similarities between Darling’s Histoplasma organism and Cryptococcus farciminosum. Cryptococcus farciminosum was reclassified as Histoplasma farciminosum in 1934, and in 1985 it was again reclassified as a variant of Histoplasma capsulatum (var. farciminosum ) (Weeks et al. 1985).William De Monbreun cultured the organism from the blood of a child suffering from an unexplained febrile disease in 1934, and demonstrated it to be a dimorphic fungus (De Monbreun 1934). De Monbreun and others reported naturally occurring histoplasmosis in a dog in 1939, and subsequently demonstrated experimentally that clinically inapparent histoplasmosis occurred in dogs (De Monbreun 1939). De Monbreun and others speculated that animals might serve as the source of histoplasmosis in human beings. However, C.W. Emmons demonstrated in 1949 that Histoplasma capsulatum is a soil saprophyte, and that inhalation of aerosolized microconidia and mycelial fragments served as the source of infection (Emmons 1949).The prevalence of histoplasmosis in endemic regions was estimated to be more than 50% based on positive skin tests for histoplasmin (Edwards et al. 1969). Active histoplasmosis has been identifi ed in up to 50% of dogs in endemic regions based on culture at necropsy of healthy animals (Turner et al. 1972a). The case prevalence of disseminated histoplasmosis at a veterinary teaching hospital in an endemic region of the mid-western USA of 43 cases in cats and 12 cases in dogs per 100,000 hospital records per year has been estimated (Clinkenbeard et al. 1988; Kaplan 1973). Dogs and cats with outdoor exposure are reportedly at greater risk for histoplasmosis than those with minimal time outdoors. However, some completely indoor cats become ill with histoplasmosis (Davies and Troy 1996; Johnson et al. 2004). Young to middle-aged dogs of hunting and sporting breeds have historically been reported at greatest risk for acquiring histoplasmosis (Selby et al. 1981). Risk factors for cats have not been systematically studied.Infection by Histoplasma capsulatum var. capsulatum is not contagious except in unusual situations. Rare cases of horizontal transmission have been reported. Horizontal transmission is associated with conjugal contraction of individuals with cutaneous lesions of the genitalia (Sills et al. 1973) and by solid organ transplantation of infected organs (Limaye et al. 2000). No documented cases of transmission from animals to human beings or vice versa have been reported. In contrast to Histoplasma capsulatum var. capsulatum, equine infection by Histoplasma capsulatum var. farciminosum is contagious and is transmitted by bites of contaminated flies or ticks as well as through skin traumatized with contaminated tack (Kohn 2006).

INCITANT ȘI INFORMATIV TOTODATĂ, titlul volumului Copilărie și parentalitate cu impact pune „în joc” trei cuvinte-cheie pentru problematica circumscrisă, gata să stimuleze curiozitatea, indiferent de vârsta, ocupația, statutul cititorului. „Paradisul pierdut al părinților” (copilăria), „misiunea” parentală – onorată sau nu, conștientizată ori ba – și, în fine, consecințele oricăruia dintre stiluri (exigent, autoritar, permisiv, neimplicat), urmări pe care le-am putea „boteza” drept amprentă fastă, „stâlp” al succesului personal și social, „marcă” a nereușitei, „dâră” adâncă în psihicul suferind al copilului, până departe, în viața de adult…, toate acestea „conviețuiesc” într-o „formulă” persuasivă care trimite la necesitatea abordării unei astfel de teme, la urgența dezbaterii ei (și sub formă editorială), la efectele (rezultatele) neapărat trăite de copil, sigur constatate de el însuși, de psiholog, învățător, medic etc., la o constantă preocupare de ordin științific, de ce nu, la un semnal de alarmă vizând decidenți de toate rangurile și responsabilitățile. „Pariul” asumat de coordonator (conf. univ. dr. Patricia Runcan) este autenticitatea, concept cu deschideri hermeneutice (din perspectivă teoretică) și provocări-capcane în privința trăirilor – mărturisirilor fiecărui subiect – actor al scrierii de față. Structurată pe trei secțiuni (părți), cartea debutează consistent prin 8 Interviuri cu profesioniști și oameni autentici, continuă cu 7 Eseuri descriptive aparținând unor masteranzi netemători de vulnerabilitatea asociată autodezvăluirii și se încheie cu Cercetări academice aplicate (rod al colaborării dintre un profesor și două absolvente cu disertații masterale pe tema tratată în Copilărie și parentalitate cu impact). „Misterul” aparent al preferinței „omului cu microfon” pentru anumiți interlocutori autentici – în pofida multor altora este măcar parțial „descâlcit” de atribute precum: deschiderea la conversații pe teme provocatoare, delicate, „spinoase”; experiența profesională de învățători, directori de școli, medici neurologi, psihoterapeuți, oameni ai bisericii, universitari; notorietatea și reputația în spațiul public; regăsirea unor valori comune (sau asemănătoare) în copilăria fiecăruia, dar și aplicate, mai apoi, în viața de părinte, profesor, terapeut, formator de opinii etc. Întrebările prestabilite (dar formulate nuanțat, pliindu-se pe structura de personalitate a „adversarului”), răspunsurile (mai concise sau mai ample), „trădând” copilării „zugrăvite” în multe culori, formulări confesive, dar și cu rol de exemplu, îndemn, dovadă, ilustrare, oglindire, lecție de viață, poveste cu tâlc, motto-ul – unul mai bine căutat decât altul – și, deloc de ignorat, ecoul fiecărei „întâlniri admirabile” în ființa „cetitorului”, laolaltă creează un „spectacol” aparte, demn de analiză. Ce este autenticitatea? (Cum să fii autentic ?) adună, din „zona” profesioniștilor, „definiții” într-un veritabil mozaic: „cu autoritate”, „stăpân pe sine”, „care acționează cum îi este sieși propriu”, „autenticitatea este grea; e singura cale de împăcare cu sine”, „în absența onestității nu există autentic”, „autenticitatea nu se determină pe axa natură-cultură”, „să fii adevărat”, „să fii original”, „să fii creativ”, „să fii valoros”. Într-un registru asemănător răspund masteranzii, formulările lor variind între: „a fi TU”, „a nu te preface”, „a-ți susține convingerile”, „a-ți cere drepturile”, „a nu-ți judeca părinții”, „a te accepta așa cum ești”, „a fi sincer mereu”, „a fi om serios”, „a inspira încredere”, „a trăi în scopul vieții, care e veșnicia”, „a fi ca mama”, „a fi același în viața privată și în cea publică”, „autenticitatea este comuniunea dintre gânduri, vorbe și fapte.” La rându-i, definirea copilăriei comportă sensibile diferențe de nuanță, esența rămânând aceeași. Dacă maturii oscilează între „copilăria este familie”, „bucurie, joacă în aer liber”, mediul în care nu trăim „hie încătro” (adică în lipsa rânduielii și a ritualurilor), „paradisul pierdut al părinților”, „poligon de încercare a duplicității, ipocriziei, snobismului, imposturii, lipsei de responsabilitate”, „poveste”, masteranzii numesc propria copilărie: „speranță”, „Nu există nu pot!”, „oglinda prin fața căreia treci ca să mai descoperi ceva din (în) tine”, „binecuvântare”, „liniște”, „colțul de rai pe pămînt”, „fundația vieții”, „o călătorie fericită într-o țară încărcată de emoție și culoare”… Observăm cu îngândurare că în discursul adulților experți – predomină bucuria, joaca, libertatea, în vreme ce o notă accentuată în „confesiunile” tinerilor masteranzi este reprezentată de maturizarea precoce, cu precădere în familiile „cu multe probleme”: părinți conflictuali, alcoolici, abuzivi, cu educație precară, indiferenți la nevoia de afectivitate și reguli rezonabile pentru buna alcătuire a caracterului copilului. Este și motivul pentru care autorul acestei prefețe nu se arată bucuros de confirmarea, în prima cercetare din finalul volumului Copilărie și parentalitate cu impact, a „armoniei” dintre stilul parental aplicat în copilăria cuiva și stilul parental internalizat de subiectul educației și exersat, la rându-i, asupra propriului descendent, după cum, nici de concluzia (ca validare a ipotezei celei din urmă cercetări) conform căreia relația de atașament din copilărie influențează în mare măsură relația de atașament a unei mame cu copilul său. Combinația fericită dintre parentalitatea autentică și copilăria ziditoare nu se constată la tot pasul. Chiar dacă valorile cultivate de familiile-nucleu sau extinse sunt dispuse într-un registru pozitiv generos (bunătate, siguranță, solidaritate, încredere, libertate, dragoste și justiție, limite raționale, principialitate, corectitudine, disciplină, partajare frățească, cinste, respect, bun simț, iubirea față de semeni, răbdare, adevăr, modestie, mediu creștin ș.a. – cum se vede în mărturiile din cartea în discuție) prea adesea, întâlnim fractura între ce e bine de făcut și răul care se petrece în relațiile interpersonale din universul familiei. Uneori, neștiința este cea dintâi cauză. Alteori, o „arhitectură” defectă a personalității părintelui. Nu rareori, influențe nepotrivite din afara mediului educațional primar. Traumele din copilărie ale genitorilor, nerezolvate la vreme, reprezintă un teribil element perturbator pentru copilăria și viitoarea viață de adult a celor mici. Incidența tot mai accentuată a familiilor disfuncționale face tot mai rar valabil adevărul: „Din familii rele ies copii buni” (însă cu o dublă condiție, echilibrul și selectivitatea dovedite de copil). Desigur, teoreticienii și practicienii avertizează și „repară”, colaborează și se luptă cu varii ipostaze ale ignoranței și stricăciunilor avându-i ca autori pe părinți. Nu-i deajuns. Nu-i mereu la timp. Nu e pentru „toată lumea” copiilor afectați. Nu e cu asumarea și sprijinul tuturor părinților. Nu e, în toată clipa, cu toate resursele (profesioniști, instrumente, bani) trebuincioase celor mai bune terapii și rezultate. Din păcate, în lumea reală, atât de multe nu se pot! Conf. univ. dr. Ștefania Bejan, Universitatea “Al. I. Cuza” din Iași