Neonatal functional treatment for Pierre Robin Sequence

Objective: Pierre Robin Sequence (PRS) is a heterogeneous pathological condition characterized by the coexistence of micrognathia, glossoptosis, and cleft palate, resulting in upper airway tract obstruction. Among the treatment modalities, the orthodontic approach is one part of the comprehensive care of those patients and will be present in the treatment modalities during all the growth period of the child.Methods: All patients with PRS observed in the period 2013-2017 were treated with a definite functional approach. The results were retrospectively analyzed with regard to functional outcome, total treatment time, and number of plates provided for a single patient.Results: In all the patients, the indicated treatment protocol has been applied as early impression and plate supply, stimulation of bottle feeding with the use of the plate, eventual substitution of the plate if no more adequate to the transverse and sagittal growth of the palate, and continuing the use until the surgical closure of the cleft. All the patients showed a positive outcome to the proposed treatment approach, evaluated with regard to the incidence of feeding improvement and weight gain, to the limit for the surgical phase, in the absence of adverse effects.Conclusion: The use of a functional obturator plate, removing functional alterations to mandibular growth, reduces and, in some cases, eliminates the need for surgical intervention. As also stated in the literature, if despite the presence of the plate nutritional problems persist, immediate different surgical approaches, mainly mandibular osteodistraction, become necessary

The endocannabinoid 2-AG controls skeletal muscle cell differentiation via CB1 receptor-dependent inhibition of Kv7 channels.

Little is known of the involvement of endocannabinoids and cannabinoid receptors in skeletal muscle cell differentiation. We report that, due to changes in the expression of genes involved in its metabolism, the levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) are decreased both during myotube formation in vitro from murine C2C12 myoblasts and during mouse muscle growth in vivo. The endocannabinoid, as well as the CB1 agonist arachidonoyl-2-chloroethylamide, prevent myotube formation in a manner antagonized by CB1 knockdown and by CB1 antagonists, which, per se, instead stimulate differentiation. Importantly, 2-AG also inhibits differentiation of primary human satellite cells. Muscle fascicles from CB1 knockout embryos contain more muscle fibers, and postnatal mice show muscle fibers of an increased diameter relative to wild-type littermates. Inhibition of Kv7.4 channel activity, which plays a permissive role in myogenesis and depends on phosphatidylinositol 4,5-bisphosphate (PIP2), underlies the effects of 2-AG. We find that CB1 stimulation reduces both total and Kv7.4-bound PIP2 levels in C2C12 cells and inhibits Kv7.4 currents in transfected CHO cells. We suggest that 2-AG is an endogenous repressor of myoblast differentiation via CB1-mediated inhibition of Kv7.4 channels

remitting relapsing carbamazepine overdosage mimicking vertebrobasilar transient ischemic attacks

The objective of this article is to describe an atypical, remitting-relapsing presentation of carbamazepine toxicity due to its interaction with nebivolol. The method we use is a case report of an elderly epileptic patient in treatment with antiepileptic drugs (AEDs) and antihypertensive drugs, manifesting transient neurological symptoms in association with high blood pressure values. The case report is of a 72-year-old male by forty years of age had tonicclonic seizures related to the presence of a cerebral arteriovenous malformation. Seizures had been successfully controlled for many years by the same dosage of carbamazepine and lamotrigine, and recently total serum carbamazepine levels resulted within the "therapeutic range." He had also a history of controlled essential hypertension, but lately he manifested a scarce control of his blood pressure values. Few days after a modification of his antihypertensive therapy, the patient had two transient episodes of dysarthria, ataxia, and dizziness. At the emergency department, his blood pressure values were 190/110 mmHg, ECG and routine blood tests were normal, and a brain CT did not show acute lesions; about two hours later, his neurological examination was normal. Morning fasting carbamazepine serum levels were "normal" too; therefore, his symptoms were initially interpreted as vertebrobasilar transient ischemic attacks. However, the recurrence of similar episodes despite the normalization of his blood pressure suggested a carbamazepine intoxication. Indeed, its dosage resulted too high just in occasion of one of his attacks. A moderate reduction of carbamazepine was followed by cessation of toxicity. This case reminds us to be aware of adverse consequences of other drugs in patients assuming carbamazepine: in this case, its toxicity was consequential to a likely metabolic interaction with nebivolol

Elevated serum Neurofilament Light chain (NfL) as a potential biomarker of neurological involvement in Myotonic Dystrophy type 1 (DM1)

Background Cognitive and behavioural symptoms due to involvement of the central nervous system (CNS) are among the main clinical manifestations of Myotonic Dystrophy type 1 (DM1). Such symptoms affect patients' quality of life and disease awareness, impacting on disease prognosis by reducing compliance to medical treatments. Therefore, CNS is a key therapeutic target in DM1. Deeper knowledge of DM1 pathogenesis is prompting development of potential disease-modifying therapies: as DM1 is a rare, multisystem and slowly progressive disease, there is need of sensitive, tissue-specific prognostic and monitoring biomarkers in view of forthcoming clinical trials. Circulating Neurofilament light chain (NfL) levels have been recognized as a sensitive prognostic and monitoring biomarker of neuroaxonal damage in various CNS disorders. Methods We performed a cross-sectional study in a cohort of 40 adult DM1 patients, testing if serum NfL might be a potential biomarker of CNS involvement also in DM1. Moreover, we collected cognitive data, brain MRI, and other DM1-related diagnostic findings for correlation studies. Results Mean serum NfL levels resulted significantly higher in DM1 (25.32 +/- 28.12 pg/ml) vs 22 age-matched healthy controls (6.235 +/- 0.4809 pg/ml). Their levels positively correlated with age, and with one cognitive test (Rey's Auditory Verbal learning task). No correlations were found either with other cognitive data, or diagnostic parameters in the DM1 cohort. Conclusions Our findings support serum NfL as a potential biomarker of CNS damage in DM1, which deserves further evaluation on larger cross-sectional and longitudinal studies to test its ability in assessing brain disease severity and/or progression

Superior efficacy of a human immunodeficiency virus vaccine combined with antiretroviral prevention in simian-human immunodeficiency virus-challenged nonhuman primates

International audienc

Nahoum Index in Brachyfacial Patients: A Pilot Study

Objective:Our aim is to test the Nahoum Index as a support in the cephalometric study of vertical dimension and therapeutic orientation in adult patients suffering from Class II malocclusion, deep bite, or short face syndrome.Methods:Twenty-three patients with molar Class II and an overbite >4 mm were stratified into two groups: orthodontic (G2) and surgical orthodontic (G1). The ANB angle and Nahoum Index were calculated for cephalometric tracing pre- and post-treatment. The difference between the ANB and Nahoum Index values were analyzed using the Statistical Package for the Social Sciences software.Results:In G1, the Nahoum Index decreased from 0.954 to 0.797, and the ANB angle decreased from 5.2° to 3.2°. In G2, the Nahoum Index decreased from 0.825 to 0.817, and the ANB angle decreased from 4.4° to 4°.Conclusion:In G1, the difference between before and after treatment was significant for the Nahoum Index only. The difference between before and after values was not significant in the G2 group. It is possible to indicate the Nahoum Index of 0.934 as the limit value in case of which a patient may be treated with orthodontics only. This limit is the opposite of the limit proposed by Nahoum for vertical excess cases and respect the same interval. Therefore, we can consider the range 0.81-0.934 to indicate borderline patients, and >0.934 to indicate surgical patients. If the ratio is close to the normal value as 0.81, the treatment will be orthodontic; if it is further increased, the treatment will be surgical

Indolyl aryl sulphones as HIV-1 non-nucleoside reverse transcriptase inhibitors: synthesis, biological evaluation and binding mode studies of new derivatives at indole-2-carboxamide.

New non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are active against the commonly occurring mutations of HIV are urgently needed for the treatment of AIDS. We synthesized new NNRTIs of the indolyl aryl sulphone (IAS) family, which are endowed with high antiviral potency against HIV-1 wt (wild-type), and the Y181C and K103N-Y181C drug resistant mutant strains. Several new compounds were highly active in lymphocytes infected with primary isolates carrying the K103N-V108I-M184V and L100I-V108I mutations. The design of new IASs was based on three-dimensional quantitative structure-activity relationship (3D QSAR) studies and docking simulations. A cross-docking study was also undertaken to gain some insights in to the binding mode of the newly synthesized IASs in the wt and mutated isoforms of reverse transcriptase

Brain connectomics' modification to clarify motor and nonmotor features of myotonic dystrophy type 1

The adult form of myotonic dystrophy type 1 (DM1) presents with paradoxical inconsistencies between severity of brain damage, relative preservation of cognition, and failure in everyday life. This study, based on the assessment of brain connectivity and mechanisms of plasticity, aimed at reconciling these conflicting issues. Resting-state functional MRI and graph theoretical methods of analysis were used to assess brain topological features in a large cohort of patients with DM1. Patients, compared to controls, revealed reduced connectivity in a large frontoparietal network that correlated with their isolated impairment in visuospatial reasoning. Despite a global preservation of the topological properties, peculiar patterns of frontal disconnection and increased parietal-cerebellar connectivity were also identified in patients' brains. The balance between loss of connectivity and compensatory mechanisms in different brain networks might explain the paradoxical mismatch between structural brain damage and minimal cognitive deficits observed in these patients. This study provides a comprehensive assessment of brain abnormalities that fit well with both motor and nonmotor clinical features experienced by patients in their everyday life. The current findings suggest that measures of functional connectivity may offer the possibility of characterizing individual patients with the potential to become a clinical tool

Novel TOP3A Variant Associated With Mitochondrial Disease: Expanding the Clinical Spectrum of Topoisomerase III Alpha-Related Diseases

ObjectivesTopoisomerase III alpha plays a key role in the dissolution of double Holliday junctions and is required for mitochondrial DNA (mtDNA) replication and maintenance. Sequence variants in the TOP3A gene have been associated with the Bloom syndrome-like disorder and described in an adult patient with progressive external ophthalmoplegia. The purpose of this report is to expand the clinical phenotype of the TOP3A-related diseases and clarify the role of this gene in primary mitochondrial disorders.MethodsA 44-year-old woman was referred to our hospital because of exercise intolerance and creatine kinase increase. Muscle biopsy and a targeted next-generation sequencing (NGS) analysis were performed.ResultsA histopathologic assessment documented a mitochondrial myopathy, and a molecular analysis revealed a novel homozygous variant in the TOP3A gene associated with multiple mtDNA deletions.DiscussionThis case suggests that TOP3A is one of the several nuclear genes associated with mtDNA maintenance disorder and expands the spectrum of its associated phenotypes, ranging from a clinical condition defined Bloom syndrome-like disorder to canonical mitochondrial syndromes

Unmanned aerial vehicle to estimate nitrogen status of turfgrasses

Spectral reflectance data originating from Unmanned Aerial Vehicle (UAV) imagery is a valuable tool to monitor plant nutrition, reduce nitrogen (N) application to real needs, thus producing both economic and environmental benefits. The objectives of the trial were i) to compare the spectral reflectance of 3 turfgrasses acquired via UAV and by a ground-based instrument; ii) to test the sensitivity of the 2 data acquisition sources in detecting induced variation in N levels. N application gradients from 0 to 250 kg ha-1 were created on 3 different turfgrass species: Cynodon dactylon x transvaalensis (Cdxt) Patriot, Zoysia matrella (Zm) Zeon and Paspalum vaginatum (Pv) Salam. Proximity and remote-sensed reflectance measurements were acquired using a GreenSeeker handheld crop sensor and a UAV with onboard a multispectral sensor, to determine Normalized Difference Vegetation Index (NDVI). Proximity-sensed NDVI is highly correlated with data acquired from UAV with r values ranging from 0.83 (Zm) to 0.97 (Cdxt). Relating NDVI-UAV with clippings N, the highest r is for Cdxt (0.95). The most reactive species to N fertilization is Cdxt with a clippings N% ranging from 1.2% to 4.1%. UAV imagery can adequately assess the N status of turfgrasses and its spatial variability within a species, so for large areas, such as golf courses, sod farms or race courses, UAV acquired data can optimize turf management. For relatively small green areas, a hand-held crop sensor can be a less expensive and more practical option