Maddalena La Montagna

Relationships of Dietary Patterns, Foods, and Micro- and Macronutrients with Alzheimer's Disease and Late-Life Cognitive Disorders: A Systematic Review

In the last decade, the association between diet and cognitive function or dementia has been largely investigated. In the present article, we systematically reviewed observational studies published in the last three years (2014-2016) on the relationship among dietary factors and late-life cognitive disorders at different levels of investigation (i.e., dietary patterns, foods and food-groups, and dietary micro- and macronutrients), and possible underlying mechanisms of the proposed associations. From the reviewed evidence, the National Institute on Aging-Alzheimers Association guidelines for Alzheimers disease (AD) and cognitive decline due to AD pathology introduced some evidence suggesting a direct relation between diet and changes in the brain structure and activity. There was also accumulating evidence that combinations of foods and nutrients into certain patterns may act synergistically to provide stronger health effects than those conferred by their individual dietary components. In particular, higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline. Moreover, also other emerging healthy dietary patterns such as the Dietary Approach to Stop Hypertension (DASH) and the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) diets were associated with slower rates of cognitive decline and significant reduction of AD rate. Furthermore, some foods or food groups traditionally considered harmful such as eggs and red meat have been partially rehabilitated, while there is still a negative correlation of cognitive functions with saturated fatty acids and a protective effect against cognitive decline of elevated fish consumption, high intake of monounsaturated fatty acids and polyunsaturated fatty acids (PUFA), particularly n-3 PUFA.

Varicella within a Prior Immunization Reaction Site: Another Example of "Isovaccinetopic Response".

To the Editor: We read with great interest the report by Wu et al (1) in which they describe an interesting case of varicella appearing within a prior immunization reaction site after pentavalent vaccination in the left anterior thigh of an 18-month-old boy. They refer to Wolf’s isotopic response as a possible pathogenic explanation for the specific distribution of varicella lesions in this child. We agree with Piccolo and Russo (2), that this is not an example of Wolf’s isotopic response. Wolf’s postherpetic isotopic response (PHIR) refers to the occurrence of a new skin disorder at the site of a previous and already healed herpetic eruption (herpes zoster in most cases) (2), not any prior healed unrelated dermatologic condition. In this case, the clinical event that preceded the appearance of varicella lesions was a vaccine-induced immunization reaction, not a herpetic infection, which is the essential element of PHIR. As Piccolo et al suggest, this case is an example of immunocompromised cutaneous district (ICD) (3), which refers to a locoregional cutaneous immune dysregulation deriving from a prior damaging event that has made a skin area prone to the local onset of immunity-related eruptions or skin disorders (3). The factors responsible for localized immune dysregulation are multifarious (4–20) and include chronic lymphatic stasis, herpetic infections, ionizing or ultraviolet radiation, burns, trauma (especially amputation), tattooing, intradermal vaccinations (as happened in this case), and others of disparate nature. A recent classification of isomorphic and isotopic skin reactions (19,20) proposed a new terminology to indicate each specific cause responsible for the occurrence of an ICD and has encompassed additional conditions (isotattootopic, isomosaictopic, isovaccinetopic, isoneuraltopic, isolymphostatic response and nonresponse) that had not been defined previously (20). According to this new categorization (20), the case of Wu et al (1) can be seen as a typical example of isovaccinetopic response. We thank the authors for giving us the opportunity to discuss such a complex and interesting topic. REFERENCES

Facial flat warts in a young patient with a previous trauma: an example of isotraumatopic response.

Dyschromatosis symmetrica hereditaria by ADAR1 mutations and viral encephalitis: a hidden link? Int J Dermatol 2013; 52: 1582–1584. 8 Liu Q, Wang Z, Wu Y, et al. Five novel mutations in the ADAR1 gene associated with dyschromatosis symmetrica hereditaria. BMC Med Genet 2014; 15: 69. 9 Okamura K, Abe Y, Fukai K, et al. Mutation analyses of patients with dyschromatosis symmetrica hereditaria: ten novel mutations of the ADAR1 gene. J Dermatol Sci 2015; 79: 88–90. 10 Xu XG, Lv Y, Zhai JL, et al. Two novel mutations of the ADAR1 gene in Chinese patients with dyschromatosis symmetrica hereditaria successfully treated with fractional CO2 laser. J Eur Acad Dermatol Venereol 2015. doi: 10.1111/jdv.13090. [Epub ahead of print].

Hidradenitis suppurativa associated with squamous cell carcinoma: an example of an isoscartopic response

activated partial thromboplastin time within the normal ranges. We did not perform debridement, considering the prolonged effects of antiplatelet therapy despite its discontinuation. Skin overlying the hematoma became completely necrotic at 13 days after onset (Fig. 2b) and was removed naturally. The wound was covered by granulation tissue at 21 days (Fig. 2c) and reconstituted by split-thickness skin grafting at 31 days. In a review of 34 cases of DDH, Kaya et al. reported that deep incision or surgical debridement was performed in all cases. However, the present case showed irreversible necrotic changes twice during hospitalization. Considering the low possibility of rescue for skin tissue overlying the hematoma and the high risk of bleeding due to the prolonged effects of antiplatelet agents, early debridement does not appear to always be the best policy. On the other hand, we performed debridement in the late phase of the first episode but not for the second episode. The fact that both outcomes were similar suggests that debridement at least in the late phase of first case may be skipped, particularly when the patient shows a tendency to bleed and no signs of infection.

Pharmacogenetics of neurological and psychiatric diseases at older age: has the time come?

ABSTRACT Introduction: In recent years, a number of pharmacological approaches for treating neuropsychiatric conditions at older age have proven to be inadequate. The resulting increased prevalence of therapeutic failures (TF) and a worsening of clinical symptoms often linked to adverse reactions (ADRs), are perhaps among the major causes of the increasing rate of hospitalizations and institutionalizations observed in these patients. Areas covered: This review underlines the importance of pharmacogenetic data to fingerprint the pharmacological treatment of neuropsychiatric late-life conditions throughout the analysis of metabolizing enzymes and transporters of psychotropic drugs, mainly those of the cytochrome P450 (CYP) family. Pharmacodynamic response measures as treatment effects mediated through targets (i.e., receptors in the brain) may also contribute to this image. Expert opinion: CYP genetics is the basis of a continuum on which environmental and physiological factors act, modeling the phenotype observed in clinical practice with advancing age. Furthermore, other specific polymorphic genes influence drug response through differential effects of their functional genetic variants. The known genotypes associated with an altered metabolizer status and drug transporters may help clinical decision-making to avoid concomitant treatments, reduce therapeutic attempts and increase drug safety in neuropsychiatric conditions in older age, after controlling for other clinical variables.

Empathy and attitudes towards mental illness among Italian medical students

ABSTRACT There is a growing interest regarding the attitudes of medical students towards people with mental illness, since discrimination and stigma may affect healthcare workers and education should be aimed to improve empathy and attitudes at medical school level. A cross-sectional study was conducted at medical schools in Rome and Foggia (Italy). We recruited 339 medical students who completed an anonymous self-report questionnaire including sociodemographic data, the 40-item Community Attitudes toward the Mentally Ill scale (CAMI) and the 60-item Baron Cohen’s Empathy Quotient. The questionnaires were administered before and after the yearly academic course of psychiatry. This study shows a significant improvement in some CAMI items and total score after the yearly academic course of psychiatry among medical students, especially among those who had personal experience with mentally ill people (including the training in a psychiatric ward). Female students reported higher empathy quotient and CAMI scores. Students who preferred medical disciplines to surgical ones seemed to be less stigmatizing towards mental illness. Our results confirm evidence from the scientific literature about medical students’ attitudes towards mental illness and highlight that the improvements in the attitudes increased improving students’ psychiatric knowledge, both theoretical and practical.

Pharmacotherapy for the treatment of depression in patients with alzheimer’s disease: a treatment-resistant depressive disorder

ABSTRACT Introduction: Pharmacotherapy for the treatment of depressive disorders in Alzheimer’s Disease (AD) represents a clinical challenge. pharmacological options are often attempted after a period of watchful waiting (8–12 weeks). monoaminergic antidepressant drugs have shown only modest or null clinical benefits, maybe because the etiology of depressive symptoms in ad patients is fundamentally different from that of nondemented subjects. Areas covered: The following article looks at the selective serotonin reuptake inhibitor sertraline, which is one of the most frequently studied antidepressant medications in randomized controlled trials (RCTs). It also discusses many other pharmacological approaches that have proven to be inadequate (antipsychotics, acetylcholinesterase inhibitors, anticonvulsants, hormone replacement therapy) and new drug classes (mainly affecting glutamate transmission) that are being studied for treating depression in AD. It also gives discussion to the phase II RCT on the alternative drug S47445 and the potential effect on cognition of the multimodal antidepressant vortioxetine in older depressed patients. Finally, it discusses the N-methyl-D-aspartate antagonist ketamine. Expert opinion: The present RCT methodologies are too disparate to draw firm conclusions. Future studies are required to identify effective and multimodal pharmacological treatments that efficiently treat depression in AD. Genotyping may boost antidepressant treatment success.

Hidradenitis suppurativa complicated by squamous cell carcinoma: isoscartopic response

Dear Editors, We read with great interest the report recently published in the International Wound Journal by Jourabchi et al., (1) which describes a patient with a 53-year history of hidradenitis suppurativa (HS) involving the perineum and buttocks complicated by squamous cell carcinoma (SCC), requiring multiple surgical resections and radiotherapy (1). HS is a chronic, inflammatory, debilitating skin disease characterised by painful, inflamed lesions in apocrine gland-bearing areas of the body, most commonly the axillary, inguinal and anogenital regions (2). The authors review 80 cases of SCC complicating HS found in the English literature (1). They state that case reports and studies suggest that the human papilloma virus (HPV) and smoking may be risk factors associated with SCC in HS (1). Furthermore, according to Jourabchi et al.’s opinion, consideration should be given to the increasing use of biological immunosuppressants in HS and the association between chronic immunosuppression and SCC as beta-HPV is activated under conditions of immune suppression (1). Jourabchi et al. observe the highly aggressive nature of SCC in HS and its likelihood of rapid progression, recurrence, metastasis and mortality, recommending an aggressive approach to management at the time of SCC diagnosis in HS (1). However, Jourabchi et al. do not fully clarify all the pathomechanisms involved in the occurrence of SCC in skin areas affected by HS (1). The authors do not mention the possible occurrence of SCC on HS because of the disruption of lymph microcirculation (that hinders the normal trafficking of immunocompetent cells) and damage to peripheral nerve endings (that release immunity-related peptides) that can occur in scarred skin areas affected by HS (2). In fact, the immunological behaviour of a scarred site is different from that of the rest of the body (2). Many times, HS can provoke the presence of scars (2), thus altering the local interplay between immune cells conveyed by lymph vessels and neuromediators running along peripheral nerve fibres. Depending on which of the neurotransmitters and immune cells are involved, the destabilisation could be either defective, thus predisposing to infections and tumours (such as SCC), or excessive, thus favouring the occurrence of some immune disorders or dysimmune reactions at the sites ‘marked’ by scarring (2). In our opinion, this concept could represent another reading key of this case and could be an additional mechanism for the SCC development. The injuring events capable of rendering a skin region potentially immunodestabilised are various, numerous and, most of the times, identifiable by means of a careful clinical history (2–22). According to a new categorisation of isomorphic and isotopic skin reactions (21,22), the report of Jourabchi et al. could be seen as a typical example of ‘isoscartopic response’ (2,14). We thank the authors for giving us the opportunity to discuss such a complex and interesting topic.

Evaluation of skin disorders of lower limb amputation sites: is there a common denominator?

tional work at school. Questions on the total number of sexual partners and age of first sexual intercourse should be added to the survey. The 5% prevalence of HPV vaccination in our students is similar to data from other European countries lacking national HPV vaccination programs. Our findings showed poor understanding of HPV-related cervical cancer prevention in medical students – what chance has the general population of young women? An HPV-related cancer preventive campaign is needed. Broader studies on HPV-related cancer awareness and vaccination in young women are needed so that when vaccination is proposed, there will be a better understanding.

Lichen planus after rabies vaccination: an example of isovaccinetopic response.

isovaccinetopic response Editor, We read with great interest the report recently published in this journal by Ozbagcivan et al., which describes a young patient affected by lichen planus developing after administration of the rabies vaccine. We speculate that Ozbagcivan et al.’s report is a striking example of the “immunocompromised cutaneous district” (ICD). The injuring events capable of rendering a skin region a potential ICD are various, numerous, and most of the times identifiable by means of a careful clinical history. Ample documentation of multifarious disorders (infectious, neoplastic, immune) appearing in ICDs was delineated by Ruocco et al. in 2009. In the following 8 years, what was a “novel” pathogenic concept has been extended to an enlarging variety of clinical conditions. A recent classification of isomorphic and isotopic skin reactions has proposed a newly coined terminology to indicate each specific cause responsible for the occurrence of an ICD and has encompassed additional conditions that had not been defined previously. According to this new categorization, the report by Ozbagcivan et al. can be seen as an example of “isovaccinetopic response,” which can be defined as a new skin disease that appears at the site of previously diseased or injured (due to previous vaccination) skin. In this peculiar case, the lichenoid eruption spread and generalized later on the trunk, extremities, face, and palmoplantar surfaces. Disruption of lymph microcirculation and damage to peripheral nerve endings could have occurred in the young patient’s vaccinated skin, thus altering the local interplay between immune cells conveyed by lymph vessels and neuromediators running along peripheral nerve fibers. This destabilization could have been excessive in the patient reported by Ozbagcivan et al., thus predisposing him to a cutaneous dysimmune disease (such as lichen planus). We thank the authors for giving us the opportunity to discuss such a complex and interesting topic.