Behavioral guidance for improving dental care in autistic spectrum disorders.

Introduction: Autism spectrum disorders (ASDs) impair many aspects of everyday life and may prevent access to dental care, often limiting it to emergencies. Impaired oral health has long-lasting negative consequences on health status and on the acquisition of oral habits (e.g., oral respiration and grinding) or competencies (e.g., proper speech production). Children with ASD may be scared in the dental setting, which is rich in sensory stimuli and requires physical contact. Due to their behavioral manifestations, they represent a challenge for dentists and hygienists. We created a dedicated pathway with behavioral support for children with ASD to allow dental care and possibly limit the use of general anesthesia. Methods: We evaluated the effects of behavioral support in a quasi-experimental design by comparing two groups of children with ASD. The first group (n = 84) was visited every 2 months for 3 years and received additional support (visual aids, caregiver training, and longer visit duration). A control group, matched for age and sex, was visited at least twice a year or more, if needed, according to standard healthcare guidelines. Results: Compliance with the schedule was high throughout the 3 years. The degree of collaboration significantly improved after 1 year in the supported group, while the control group did not change. At the end of the study, collaboration remained significantly higher than at the beginning in the supported group. Half of dental treatments were possible without general anesthesia in supported children. No adverse effect was apparent on collaboration due to COVID-19 restrictions. Discussion: Behavioral techniques improved the compliance of ASD children to regular dentistry visits and treatment. Furthermore, oral hygiene at home was similarly improved, addressing oral health from a lifelong perspective.

The function of specialized pro-resolving endogenous lipid mediators, vitamins, and other micronutrients in the control of the inflammatory processes: Possible role in patients with SARS-CoV-2 related infection.

Inflammation is an essential protective response against harmful stimuli, such as invading pathogens, damaged cells, or irritants. Physiological inflammation eliminates pathogens and promotes tissue repair and healing. Effective immune response in humans depends on a tightly regulated balance among inflammatory and anti-inflammatory mechanisms involving both innate and adaptive arms of the immune system. Excessive inflammation can become pathological and induce detrimental effects. If this process is not self-limited, an inappropriate remodeling of the tissues and organs can occur and lead to the onset of chronic degenerative diseases. A wide spectrum of infectious and non-infectious agents may activate the inflammation, via the release of mediators and cytokines by distinct subtypes of lymphocytes and macrophages. Several molecular mechanisms regulate the onset, progression, and resolution of inflammation. All these steps, even the termination of this process, are active and not passive events. In particular, a complex interplay exists between mediators (belonging to the group of Eicosanoids), which induce the beginning of inflammation, such as Prostaglandins (PGE2), Leukotrienes (LT), and thromboxane A2 (TXA2), and molecules which display a key role in counteracting this process and in promoting its proper resolution. The latter group of mediators includes: ω-6 arachidonic acid (AA)-derived metabolites, such as Lipoxins (LXs), ω -3 eicosapentaenoic acid (EPA)-derived mediators, such as E-series Resolvins (RvEs), and ω -3 docosahexaenoic (DHA)-derived mediators, such as D-series Resolvins (RvDs), Protectins (PDs) and Maresins (MaRs). Overall, these mediators are defined as specialized pro-resolving mediators (SPMs). Reduced synthesis of these molecules may lead to uncontrolled inflammation with possible harmful effects. ω-3 fatty acids are widely used in clinical practice as rather inexpensive, safe, readily available supplemental therapy. Taking advantage of this evidence, several researchers are suggesting that SPMs may have beneficial effects in the complementary treatment of patients with severe forms of SARS-CoV-2 related infection, to counteract the "cytokine storm" observed in these individuals. Well-designed and sized trials in patients suffering from COVID-19 with different degrees of severity are needed to investigate the real impact in the clinical practice of this promising therapeutic approach.

SARS-CoV-2 vaccines: What we know, what we can do to improve them and what we could learn from other well-known viruses.

In recent weeks, the rate of SARS-CoV-2 infections has been progressively increasing all over the globe, even in countries where vaccination programs have been strongly implemented. In these regions in 2021, a reduction in the number of hospitalizations and deaths compared to 2020 was observed. This decrease is certainly associated with the introduction of vaccination measures. The process of the development of effective vaccines represents an important challenge. Overall, the breakthrough infections occurring in vaccinated subjects are in most cases less severe than those observed in unvaccinated individuals. This review examines the factors affecting the immunogenicity of vaccines against SARS-CoV-2 and the possible role of nutrients in modulating the response of distinct immune cells to the vaccination.

SARS-CoV-2: lessons from both the history of medicine and from the biological behavior of other well-known viruses.

SARS-CoV-2 is the etiological agent of the current pandemic worldwide and its associated disease COVID-19. In this review, we have analyzed SARS-CoV-2 characteristics and those ones of other well-known RNA viruses viz. HIV, HCV and Influenza viruses, collecting their historical data, clinical manifestations and pathogenetic mechanisms. The aim of the work is obtaining useful insights and lessons for a better understanding of SARS-CoV-2. These pathogens present a distinct mode of transmission, as SARS-CoV-2 and Influenza viruses are airborne, whereas HIV and HCV are bloodborne. However, these viruses exhibit some potential similar clinical manifestations and pathogenetic mechanisms and their understanding may contribute to establishing preventive measures and new therapies against SARS-CoV-2.

COVID-19, what could sepsis, severe acute pancreatitis, gender differences, and aging teach us?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a potentially life-threatening disease, defined as Coronavirus Disease 19 (COVID-19). The most common signs and symptoms of this pathological condition include cough, fever, shortness of breath, and sudden onset of anosmia, ageusia, or dysgeusia. The course of COVID-19 is mild or moderate in more than 80% of cases, but it is severe or critical in about 14% and 5% of infected subjects respectively, with a significant risk of mortality. SARS-CoV-2 related infection is characterized by some pathogenetic events, resembling those detectable in other pathological conditions, such as sepsis and severe acute pancreatitis. All these syndromes are characterized by some similar features, including the coexistence of an exuberant inflammatory- as well as an anti-inflammatory-response with immune depression. Based on current knowledge concerning the onset and the development of acute pancreatitis and sepsis, we have considered these syndromes as a very interesting paradigm for improving our understanding of pathogenetic events detectable in patients with COVID-19. The aim of our review is: 1)to examine the pathogenetic mechanisms acting during the emergence of inflammatory and anti-inflammatory processes in human pathology; 2)to examine inflammatory and anti-inflammatory events in sepsis, acute pancreatitis, and SARS-CoV-2 infection and clinical manifestations detectable in patients suffering from these syndromes also according to the age and gender of these individuals; as well as to analyze the possible common and different features among these pathological conditions; 3)to obtain insights into our knowledge concerning COVID-19 pathogenesis. This approach may improve the management of patients suffering from this disease and it may suggest more effective diagnostic approaches and schedules of therapy, depending on the different phases and/or on the severity of SARS-CoV-2 infection.

Paradoxical relationship between proton pump inhibitors and COVID-19: A systematic review and meta-analysis.

BACKGROUND: The proton pump inhibitors (PPIs), used to reduce gastric acid secretion, represent one of the most widely used pharmaceutical classes in the world. Their consumption as a risk factor for the evolution of severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been investigated as well as the mortality of these patients. These risks also appear to be linked to the duration and the dosage. On the other hand, several studies have emerged with regard to the protective or therapeutic effects of these drugs. More and more evidence underlines the immunomodulatory and anti-fibrotic role of PPIs. In addition, their ability to alkalize the contents of endosomes and lysosomes serves as an obstacle to the entry of the virus into the host cells. AIM: To identify studies on the relationship between the intake of PPIs and coronavirus disease 2019 (COVID-19) in patients affected by SARS-CoV-2 infection, with the main objective of evaluating the outcomes related to severity and mortality. METHODS: A literature review was performed in November 2020. The MEDLINE/PubMed, Cochrane Library, EMBASE and Google Scholar databases were searched for all relevant articles published in English on this topic. The search terms were identified by means of controlled vocabularies, such as the National Library of Medicine's MESH (Medical Subject Headings) and keywords. The MESH terms and keywords used were as follows: "COVID-19", "proton pump inhibitors", "PPIs", "SARS-CoV-2", "outcomes", "severity" and "mortality". The inclusion criteria regarding the studies considered in our analysis were: meta-analysis, case-control, hospital-based case-control, population-based case-control, retrospective studies, online survey, as well as cohort-studies, while articles not published as full reports, such as conference abstracts, case reports and editorials were excluded. We tried to summarize and pool all the data if available. RESULTS: A total of 9 studies were found that described the use of PPIs, of which only 5 clearly reported the severity and mortality data in SARS-CoV-2 patients. Our pooled incidence analysis of severe events did not differ between patients with and without PPIs (odds ratio 1.65, 95% confidence interval: 0.62-4.35) (P = 0.314), or for mortality (odds ratio 1.77, 95% confidence interval: 0.62-5.03) (P = 0.286). CONCLUSION: Detailed and larger case studies are needed to accurately understand the role of PPIs in this viral infection.

The rationale for a multi-step therapeutic approach based on antivirals, drugs and nutrients with immunomodulatory activity in patients with coronavirus-SARS2-induced disease of different severities.

In December 2019, a novel human-infecting coronavirus, named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), was recognised to cause a pneumonia epidemic outbreak with different degrees of severity in Wuhan, Hubei Province in China. Since then, this epidemic has spread worldwide; in Europe, Italy has been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, few studies about SARS-CoV-2 concerning its immunopathogenesis and treatment are available. On the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82 % of genome homology) and that its characteristics, like the modality of transmission or the type of the immune response it may stimulate, are still poorly known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analysed: (1) the structure of SARS-CoV-2 and SARS-CoV; (2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the cytokine release syndrome; (3) the modification of the cell microRNome and of the immune response in patients with SARS infection; and (4) the possible role of some fat-soluble compounds (such as vitamins A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.

Gingival overgrowth induced by anticonvulsant drugs: A cross-sectional study on epileptic patients.

OBJECTIVE: Our aim was to estimate the prevalence of gingival overgrowth (hyperplasia) and to determine whether active molecules affect the severity of overgrowth in a group of epileptic patients. BACKGROUND: The effects of phenytoin on oral health have been explored in different studies, yet little information is available on other antiepileptic drugs. METHODS: Data were collected from 213 subjects of both sexes, from 5 to 80 years. Patients taking the same antiepileptic therapy for at least 1 year and meeting the inclusion criteria of the study (n = 162) were subjected to measurement of gingival overgrowth according to the modified Harris and Ewalt classification and O'Leary's plaque control record (OLR). Descriptive statistics were calculated. Data were analyzed using Pearson's r correlation coefficient and chi-square test. Significance level was set at 5%. RESULTS: The active drugs lamotrigine, oxcarbazepine, and phenobarbital were significantly associated with gingival overgrowth in 61%, 71%, and 53% of cases, respectively, and phenytoin, valproic acid, and carbamazepine in 50%, 44%, and 32% of cases, respectively. CONCLUSION: Different antiepileptic molecules may be related to gingival overgrowth. In addition to phenytoin, also lamotrigine, oxcarbazepine, and phenobarbital were associated with increased prevalence of gingival overgrowth. In the management of epileptic patients, dentists should take into account different drugs as possible causes for gingival overgrowth and warn for possible alternatives.

Involvement of the exocrine pancreas during COVID-19 infection and possible pathogenetic hypothesis: a concise review.

The gastrointestinal system may be affected by COVID-19 infection with an incidence variable from 3% up to 79%. Several works show that the pancreas, both in its exocrine and endocrine function, can be affected by this viral infection, although this organ has been poorly analyzed in this current epidemic context. This mini-review aims to provide a summary of available studies on exocrine pancreas involvement during COVID-19 infection. A search through MEDLINE/PubMed was conducted on the topic in hand. With regard to exocrine function, some studies highlight the presence of an associated hyperenzymemia (hyperamylasemia, hyperlipasemia), while others describe isolated and rare cases of acute pancreatitis. More attention should be paid to pancreatic impairment in subjects with COVID-19, as this may prove to be one of the elements aggravating its clinical course. Indeed, acute pancreatitis, especially when presenting in severe forms with hyperstimulation of the pro-inflammatory response, may represent a crucial factor in the progression of COVID-19, entailing both an increase in hospitalization days and in mortality rate.

Cytokine storm in aged people with CoV-2: possible role of vitamins as therapy or preventive strategy.

BACKGROUND: In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a "public health emergency of international concern". A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. METHODS: We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. RESULTS: SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. CONCLUSIONS: Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.

Symmetry of dental agenesis in Down Syndrome children.

BACKGROUND/PURPOSE: Down syndrome (DS) may affect the mouth, influencing its function, feeding and hence overall health status. We aim at investigating the frequency and type of dental agenesis in a school-age DS sample, evaluating gender, laterality, upper or lower side, and mono- or bi-laterality. MATERIALS AND METHODS: Oral clinical and radiological exams were performed. Forty-six (20 female and 26 male) panoramic radiographs, done when DS patients were 8-12 years old, were examined, from patients between 3 and 25 years old at the first visit. RESULTS: The percentage of missing teeth was compared with chi-squared test: 65% of patients presented agenesis of one or more teeth. The most frequently missing teeth were the upper left lateral incisor, the lower second premolars and the upper right lateral incisor. Usually, the absence was bilateral. There was no difference between sexes, between mandible and maxilla, either in the left or in the right side. CONCLUSION: A high occurrence of dental agenesis was observed in DS patients: some teeth were mostly affected and bilateral agenesis was frequent. Due to the high prevalence of teeth agenesis in DS patients, special care is devised for correct development of oral functions and for avoidance of oral pathologies.

Hypothermia reduces seizure burden and improves neurological outcome in severe hypoxic-ischemic encephalopathy: an observational study.

AIM: To evaluate the antiepileptic effect of hypothermia and its association with neurological outcome in infants with moderate and severe hypoxic-ischemic encephalopathy (HIE). METHOD: We compared polygraphic electroencephalography monitoring and outcome data in 39 cooled and 33 non-cooled term newborn infants, born between January 2005 and March 2013, and hospitalized because of signs of asphyxia and moderate to severe HIE. RESULTS: Cooled newborn infants had fewer seizures (14/39 vs 20/33 p=0.036) and status epilepticus (7/39 vs 13/33, p=0.043), a lower mean duration of seizures (18mins vs 133mins, p=0.026), fewer administered antiepileptic drugs (median 0 vs 1, p=0.045), and more commonly a good outcome at 24 months (normal/mild motor impairment in 32/39 vs 16/33, p=0.003). Seizure burden (accumulated duration of seizures over a defined period) in cooled patients with both moderate (0.0 vs 0.1; p=0.045) and severe HIE (0.3 vs 4.9; p=0.018) was lower than in non-cooled patients. Compared with non-cooled patients, a good outcome was more common in cooled newborn infants with severe HIE (p=0.003). INTERPRETATION: Hypothermia has an antiepileptic effect in both moderate and severe neonatal HIE. The lower seizure burden in cooled newborn infants with severe HIE is more commonly associated with normal outcome at 24 months.

Massive thymic hemorrhage and hemothorax occurring in utero.

BACKGROUND: Thymic enlargement is a common and physiological finding in children and neonates' X-rays, but it is usually asymptomatic. Occasionally it can cause respiratory distress. In most cases the aetiology of this expansion remains unclear and it is diagnosed as a thymic hyperplasia. True thymic hyperplasia is defined as a gland expansion, both in size and weight, while maintaining normal microscopic architecture. Often it is a diagnosis of exclusion and prognosis is good. Thymic haemorrhage is an unusual condition related to high foetal and neonatal mortality. CASE PRESENTATION: We report a case of spontaneous massive thymic haemorrhage in a newborn developing at birth acute respiratory distress associated with severe bilateral haemothorax. Thymic enlargement was evident after pleural evacuation and confirmed by radiographic, Computed Tomography (CT) images and Magnetic Resonance Imaging (MRI) sequences. The spontaneous resolution of this enlargement seen with CT scan and MRI sequences suggested a thymic haemorrhage; surgery was not necessary. CONCLUSION: Thymic haemorrhage should be considered in newborn infants with pleural effusion, mediastinal space enlargement and Respiratory Distress.

Fatal pneumonia following maternal HSV-1 viraemia in late pregnancy.

Neonatal Herpes simplex virus (HSV) pneumonia without apparent accompanying disseminated infection is a rare condition. We describe a case of neonatal pneumonia following maternal HSV type 1 viraemia in late pregnancy. A review of the literature shows that cases of HSV presenting as pneumonia in the first week of life are the most severe form of neonatal HSV.

Shelf life and quality study of minced tilapia with Nori and Hijiki seaweeds as natural additives.

The extraction of mechanically separated meat has emerged as an attractive process. However, it increases the incorporation of oxygen and, consequently, of flavors due to rancidity. Thus, preservatives must be added. The objective of this study was to evaluate the shelf life of minced tilapia to replace synthetic preservatives with Hijiki and Nori seaweeds extracts. The application of the extracts had no effect on the chemical composition of the minced tilapia. The seaweed extracts had inhibitory effect on total volatile base nitrogen. The minced tilapia complied with the microbiological standard set by Brazilin law. The panelists detected no differences in the rancid aroma and only minor differences were detected in the color of the products. It can be concluded that the minced tilapia with added seaweed extracts were within quality standards during frozen storage.

Prognostic value of diffusion-weighted imaging summation scores or apparent diffusion coefficient maps in newborns with hypoxic-ischemic encephalopathy.

BACKGROUND: The diagnostic and prognostic assessment of newborn infants with hypoxic-ischemic encephalopathy (HIE) comprises, among other tools, diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps. OBJECTIVE: To compare the ability of DWI and ADC maps in newborns with HIE to predict the neurodevelopmental outcome at 2 years of age. MATERIALS AND METHODS: Thirty-four term newborns with HIE admitted to the Neonatal Intensive Care Unit of Modena University Hospital from 2004 to 2008 were consecutively enrolled in the study. All newborns received EEG, conventional MRI and DWI within the first week of life. DWI was analyzed by means of summation (S) score and regional ADC measurements. Neurodevelopmental outcome was assessed with a standard 1-4 scale and the Griffiths Mental Developmental Scales - Revised (GMDS-R). RESULTS: When the outcome was evaluated with a standard 1-4 scale, the DWI S scores showed very high area under the curve (AUC) (0.89) whereas regional ADC measurements in specific subregions had relatively modest predictive value. The lentiform nucleus was the region with the highest AUC (0.78). When GMDS-R were considered, DWI S scores were good to excellent predictors for some GMDS-R subscales. The predictive value of ADC measurements was both region- and subscale-specific. In particular, ADC measurements in some regions (basal ganglia, white matter or rolandic cortex) were excellent predictors for specific GMDS-R with AUCs up to 0.93. CONCLUSIONS: DWI S scores showed the highest prognostic value for the neurological outcome at 2 years of age. Regional ADC measurements in specific subregions proved to be highly prognostic for specific neurodevelopmental outcomes.

Tensegrity model hypothesis: may this paradigm be useful to explain hepatic and pancreatic carcinogenesis in patients with persistent hepatitis B or hepatitis C virus infection?

CONTEXT: Hepatitis B (HBV) and hepatitis C virus (HCV) possess well-known oncogenic properties and may promote carcinogenesis in liver. However antigens and replicative sequences of HBV/HCV have been also detected in different extra-hepatic tissues, including the pancreas. Although epidemiological studies and meta-analyses have recently suggested that HBV/HCV may be also risk factors for pancreatic cancer and several researches have investigated the possible mechanisms and intra-/extra-cellular paths involved in pancreatic and hepatic carcinogenesis, to date, these complex processes remain largely unexplained. OBJECTIVES: In our paper, we aimed to propose a comprehensive and qualitative hypothetical model, describing how HBV/HCV may exert their oncogenic role. METHODS: We performed a systematic research of scientific literature, by searching MEDLINE, the Cochrane Library and EMBASE databases. The used keywords were: "chronic HBV/HCV", "pancreatic cancer", "liver carcinoma", "carcinogenesis mechanisms", "tensional integrity", "cytoskeleton", and "extracellular matrix". RESULTS: Taking advantage from available studies, we suggest an unifying hypothesis based on results and data, obtained from different areas of research. In particular we considered the well-defined model of tensional integrity and correlated it to changes induced by HBV/HCV in viscoelastic properties/stiffness of cellular/extracellular microenvironments. These events perturb the tightly-regulated feedback loop, which usually couples the intracellular-generated forces to substrate rigidity of extracellular compartments. Therefore, such a change strongly affects intracellular functions and cellular fate, by promoting a substantial deregulation of critical intracellular biochemical activities and genome expression. CONCLUSIONS: Our hypothesis might provide for the first time a reliable system, which correlates tensional integrity model with intra-/extra-cellular modifications, occurring in liver and pancreas during HBV/HCV-induced carcinogenesis. This approach might improve our understanding of pathogenetic mechanisms involved in the development of pancreatic and hepatic carcinogenesis , enhancing the possibility of their treatment. Furthermore, should the usefulness of this model be definitively confirmed, it might be also helpful to extend its field of application to other viruses-related cancers.

Preterm birth and developmental problems in infancy and preschool age Part II: cognitive, neuropsychological and behavioural outcomes.

Few studies focus on the neuropsychological and behavioural outcomes of preterm children at preschool age. This article reviews the most recent and relevant contributions on cognitive, neuropsychological and behavioural outcomes, and the neuroradiological findings in extremely and very preterm infants. In the first 2 years of life, cognitive impairment is common: it has an incidence of 30-40% and a higher prevalence than neuromotor and neurosensorial impairments. Recent studies report that even preterm infants with no major disabilities at preschool age perform more poorly than term peers in multiple neuropsychological domains, such as language, attention, memory, visuomotor and visuospatial processing and executive functions. The incidence and severity of problems increase with decreasing gestational age. A delayed acquisition of neuropsychological functions and/or the occurrence of behavioural problems at preschool age are likely to be predictive of the high rate of cognitive deficits at school age and in adolescence. Neuropsychological functions across multiple developmental domains should be assessed longitudinally during routine follow-up checks.

Preterm birth and developmental problems in the preschool age. Part I: minor motor problems.

Nearly half of very preterm (VP) and extremely preterm (EP) infants suffers from minor disabilities. The paper overviews the literature dealing with motor problems other than cerebral palsy (CP) during infancy and preschool age. The term "minor motor problems" indicates a wide spectrum of motor disorders other than CP; "minor" does not mean "minimal", as a relevant proportion of the preterm infants will develop academic and behavioural problems at school age. Early onset disorders consist of abnormal general movements (GMs), transient dystonia and postural instability; these conditions usually fade during the first months. They were underestimated in the past; recently, qualitative assessment of GMs using Prechtl's method has become a major item of the neurological examination. Late onset disorders include developmental coordination disorder (DCD) and/or minor neurological dysfunction (MND): both terms cover partly overlapping problems. Simple MND (MND-1) and complex MND (MND-2) can be identified and MND-2 gives a higher risk for learning and behavioural disorders. A relationship between the quality of GMs and MND in childhood has been recently described. The Touwen infant neurological examination (TINE) can reliably detect neurological signs of MND even in infancy. However, the prognostic value of these disorders requires further investigations.

Neonatal herpes simplex virus.

Herpes simplex virus is an important cause of neonatal infection, which can lead to death or long-term disabilities. Rarely in utero, the transmission frequently occurs during delivery. The disease may be disseminated, localized to the central nervous system, or involving skin, eye and/or mouth. Mortality rates markedly decreased with high-dose antiviral treatment. Diagnosis of neonatal infection is based on viral isolation from ulcerated vesicles or by scarifying mucocutaneous lesions. Recently polymerase chain reaction plays a central role for both viral detection (skin, mucosal, cerebrospinal fluid samples) and response to therapy. Vertical transmission may be decreased by prophylactic antiviral treatment.