Ketamine administration in early postnatal life as a tool for mimicking Autism Spectrum Disorders core symptoms

Autism Spectrum Disorders (ASD) core symptoms include deficits of social interaction, stereotyped behaviours, dysfunction in language and communication. Beyond them, several additional symptoms, such as cognitive impairment, anxiety-like states and hyperactivity are often occurring, mainly overlapping with other neuropsychiatric diseases. To untangle mechanisms underlying ASD etiology, and to identify possible pharmacological approaches, different factors, such as environmental, immunological and genetic ones, need to be considered. In this context, ASD animal models, aiming to reproduce the wide range of behavioural phenotypes of this uniquely human disorder, represent a very useful tool. Ketamine administration in early postnatal life of mice has already been studied as a suitable animal model resembling psychotic-like symptoms. Here, we investigated whether ketamine administration, at postnatal days 7, 9 and 11, might induce behavioural features able to mimic ASD typical symptoms in adult mice. To this aim, we developed a 4-days behavioural tests battery, including Marble Burying, Hole Board, Olfactory and Social tests, to assess repetitive and stereotyped behaviour, social deficits and anxiety-like symptoms. Moreover, by using this mouse model, we performed neurochemical and biomolecular analyses, quantifying neurotransmitters belonging to excitatory-inhibitory pathways, such as glutamate, glutamine and gamma-aminobutyric acid (GABA), as well as immune activation biomarkers related to ASD, such as CD11b and glial fibrillary acidic protein (GFAP), in the hippocampus and amygdala. Possible alterations in levels of brain-derived neurotrophic factor (BDNF) expression in the hippocampus and amygdala were also evaluated. Our results showed an increase in stereotyped behaviours, together with social impairments and anxiety-like behaviour in adult mice, receiving ketamine administration in early postnatal life. In addition, we found decreased BDNF and enhanced GFAP hippocampal expression levels, accompanied by elevations in glutamate amount, as well as reduction in GABA content in amygdala and hippocampus. In conclusion, early ketamine administration may represent a suitable animal model of ASD, exhibiting face validity to mimic specific ASD symptoms, such as social deficits, repetitive repertoire and anxiety-like behaviour

Precision Medicine in Alzheimer’s Disease: Investigating Comorbid Common Biological Substrates in the Rat Model of Amyloid Beta-Induced Toxicity

Alzheimer’s disease (AD), one of the most widespread neurodegenerative disorder, is a fatal global burden for the elder population. Although many efforts have been made, the search of a curative therapy is still ongoing. Individuating phenotypic traits that might help in investigating treatment response is of growing interest in AD research. AD is a complex pathology characterized by many comorbidities, such as depression and increased susceptibility to pain perception, leading to postulate that these conditions may rely on common biological substrates yet to be determined. In order to investigate those biological determinants to be associable with phenotypic traits, we used the rat model of amyloid beta-induced toxicity. This established model of early phase of AD is obtained by the intracerebroventricular injection of soluble amyloid beta1-42 (Aβ) peptide 7 days before performing experiments. In this model, we have previously reported increased immobility in the forced swimming test, reduced cortical serotonin levels and subtle alterations in the cognitive domain a depressive-like phenotype associated with subtle alteration in memory processes. In light of evaluating pain perception in this animal model, we performed two different behavioral tests commonly used, such as the paw pressure test and the cold plate test, to analyze mechanical hyperalgesia and thermal allodynia, respectively. Behavioural outcomes confirmed the memory impairment in the social recognition test and, compared to sham, Aβ-injected rats showed an increased selective susceptibility to mechanical but not to thermal stimulus. Behavioural data were then corroborated by neurochemical and biochemical biomarker analyses either at central or peripheral level. Data showed that the peptide injection evoked a significant increase in hypothalamic glutamate, kynurenine and dopamine content, while serotonin levels were reduced. Plasma Cystatin-C, a cysteine protease, was increased while serotonin and melatonin levels were decreased in Aβ-injected rats. Urinary levels paralleled plasma quantifications, indicating that Aβ-induced deficits in pain perception, mood and cognitive domain may also depend on these biomarkers. In conclusion, in the present study, we demonstrated that this animal model can mimic several comorbid conditions typical of the early phase of AD. Therefore, in the perspective of generating novel therapeutic strategies relevant to precision medicine in AD, this animal model and the biomarkers evaluated herein may represent an advantageous approach

Response to isolated limb perfusion and chemotherapy with epirubicin plus ifosfamide in a metastatic malignant ossifying fibromyxoid tumor

Background: Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain lineage and intermediate biological potential. It is more common in middle-aged men, usually arising from the deep tissues of the extremities. It is now established that it is a translocation related tumor, most often marked by translocation of PHF1 gene. Surgery is the mainstay of treatment and proves usually curative, although, in rarer cases the disease shows malignant features and tendency to recur both locally and at distant sites. In such cases, no standard treatment exists. Case presentation: We report on a case of malignant advanced OFMT of the hand with lung metastases responding to isolated limb perfusion with human recombinant tumor necrosis factor and melphalan and chemotherapy with epirubicin and ifosfamide. Conclusions: To our knowledge, this is the first report of activity of soft tissue sarcoma-oriented chemotherapy in advanced OFMT

"I have got something positive out of this situation": psychological benefits of caregiving in relatives of young people with muscular dystrophy.

This paper focuses on the psychological benefits of caregiving in key relatives of patients with muscular dystrophies (MD), a group of rare diseases characterized by progressive weakness and restriction of the patient's functional abilities. We describe whether relatives perceived caregiving to be a positive experience and test whether relatives' perceptions vary in relation to their view of the patient as a valued person, the degree of involvement in care, and the level of support provided by social network and professionals. The study sample included 502 key relatives of patients aged 4-25 years, suffering from Duchenne, Becker, or limb-girdle MD, in treatment for at least 6 months to one of the eight participating centers, living with at least one relative aged 18-80 years. Of key relatives, 88 % stated that they had gotten something positive out of the situation, 96 % considered their patients to be sensitive, and 94 % viewed their patients as talented. Positive aspects of caregiving were more recognized by key relatives who were more convinced that the patient was sensitive and who perceived that they received higher level of professional help and psychological social support. These results suggest that most key relatives consider that their caregiving experience has had a positive impact on their lives, despite the practical difficulties of caring for patients with MD. Professionals should help relatives to identify the benefits of caregiving without denying its difficulties. Clinicians themselves should develop positive attitudes towards family involvement in the care of patients with long-term diseases

Upper limb function in Duchenne muscular dystrophy: 24 month longitudinal data.

The aim of the study was to establish 24 month changes in upper limb function using a revised version of the performance of upper limb test (PUL 2.0) in a large cohort of ambulant and non-ambulant boys with Duchenne muscular dystrophy and to identify possible trajectories of progression. Of the 187 patients studied, 87 were ambulant (age range: 7-15.8 years), and 90 non-ambulant (age range: 9.08-24.78). The total scores changed significantly over time (p<0.001). Non-ambulant patients had lower total scores at baseline (mean 19.7) when compared to the ambulant ones (mean 38.4). They also had also a bigger decrease in total scores over 24 months compared to the ambulant boys (4.36 vs 2.07 points). Multivariate model analysis showed that the Performance of Upper Limb changes reflected the entry level and ambulation status, that were independently associated to the slope of Performance of Upper Limb changes. This information will be of help both in clinical practice and at the time of designing clinical trials

ANALISIS MUTU FISIK DAN CITARASA BEBERAPA VARIETAS KOPI ARABIKA GAYO AKIBAT PENUNDAAN PROSES PULPING

Selama abad terakhir ini pemanasan global yang terjadi berdampak terhadap peningkatan suhu. Dengan meningkatnya suhu, masa panen kopi menjadi lebih singkat. Singkatnya masa panen kopi memiliki masalah dikalangan petani karena kapasitas pemanenan yang meningkat dalam kurun waktu panen yang semakin pendek. Untuk mencapai pemanenan yang tepat waktu, petani biasanya cenderung lebih memilih menunda proses pulping karena kapasitas tenaga kerja yang terbatas. Penelitian ini bertujuan untuk mempelajari berapa lama waktu penundaan proses pulping yang masih bisa ditoleransi sehingga tidak terlalu berdampak pada mutu fisik dan citarasa yang dihasilkan dari beberapa varietas kopi. Penelitian ini menggunakan Rancangan Acak Kelompok (RAK) dengan pola faktorial yang terdiri atas 2 faktor. Faktor pertama adalah varietas kopi yang digunakan (V) yaitu V1 = Tim-tim, V2 = Bourbon dan V3 = Ateng Super. Faktor kedua adalah lama penundaan proses pulping yang dilakukan (P) yaitu P0 = 0 hari, P1 = 1 hari, P2 = 2 hari, P3 = 3 hari, P4 = 4 hari dan P5 = 5 hari. Setiap perlakuan diulang sebanyak dua kali sehingga terdapat 36 satuan percobaan. Analisis yang dilakukan meliputi: persentase buah mengapung, suhu buah selama penundaan proses pulping, densitas kamba, kadar air, biji busuk, biji hitam dan biji berwarna coklat. Serta pengujian pH seduhan kopi.Kata kunci : Kopi Arabika Gayo, mutu fisik,citarasa,penundaan proses pulping

Upper limb function in Duchenne muscular dystrophy: 24 month longitudinal data

The aim of the study was to establish 24 month changes in upper limb function using a revised version of the performance of upper limb test (PUL 2.0) in a large cohort of ambulant and non-ambulant boys with Duchenne muscular dystrophy and to identify possible trajectories of progression. Of the 187 patients studied, 87 were ambulant (age range: 7–15.8 years), and 90 non-ambulant (age range: 9.08–24.78). The total scores changed significantly over time (p<0.001). Non-ambulant patients had lower total scores at baseline (mean 19.7) when compared to the ambulant ones (mean 38.4). They also had also a bigger decrease in total scores over 24 months compared to the ambulant boys (4.36 vs 2.07 points). Multivariate model analysis showed that the Performance of Upper Limb changes reflected the entry level and ambulation status, that were independently associated to the slope of Performance of Upper Limb changes. This information will be of help both in clinical practice and at the time of designing clinical trials

"Recipe": Pratiche mediche, cosmetiche e culinarie attraverso i testi (secoli XIV-XVI)

Il volume affronta il mondo delle ricette e dei ricettari non solo sul piano delle pratiche di cura e benessere, ma in quanto inesauribile fonte di conoscenza storica, lessicale e culturale. Allestiti per venire incontro alle pi\uf9 svariate esigenze di individui e comunit\ue0, i ricettari offrono esempi istruttivi dei linguaggi tecnici in uso all'epoca (botanica, farmacia, scienze), ma anche della lingua d\u2019uso, e spesso una chiave d\u2019accesso per la comprensione di importanti aspetti della vita quotidiana, quali il viaggio o la moda femminile (si pensi alle pratiche di mascalcia, alle varie forme di cosmesi, ai rituali legati a magia e superstizione)