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Purpose: To evaluate the clinical outcome of deantigenated equine bone (DEB) grafts in a series of patients treated with DEB at six months postaugmentation., Materials and Methods: One hundred DEB grafts were inserted in 81 patients between January 2004 and December 2006. Thirty-two DEBs were blocks and 68 were granules (52 sinus lift and 16 guided bone regeneration [GBR] procedures performed). A total of 147 implants were inserted. A Pearson chi-square test was used to detect any statistically significant correlation between the studied variables and early and/or late failures., Results: There were 6 early and 26 late graft failures and another 16 failures after prosthesis placement. The overall failure rate was 25% in the GBR procedures, 31.9% in sinus lift, and 54.3% with blocks, for a total complication rate of 39.5%. A statistically significant relation was detected with respect to graft type and early complications (p = .005), with a worse outcome for DEB blocks compared to granules. After provisional prosthesis restoration, 23 implants were lost, and another 41 failed after definitive prosthesis delivery, for an overall failure rate of 43.5%. The follow-up period was 3 years after surgery., Conclusions: DEB grafting material had a very high rate of complications. Blocks had more than 50% failures, mainly in the immediate postoperative period. Other procedures such as GBR and sinus lift also showed more than 25% infections and resorption, and late failures (i.e., after-implant placement) were also common. Our results show that DEB is less than ideal for crestal bone reconstruction., (© 2013 Wiley Periodicals, Inc.)

Hybridization and strand displacement kinetics determine the evolution of the base paired configurations of mixtures of oligonucleotides over time. Although much attention has been focused on the thermodynamics of DNA and RNA base pairing in the scientific literature, much less work has been done on the time dependence of interactions involving multiple strands, especially in RNA. Here we provide a study of oligoribonucleotide interaction kinetics and show that it is possible to calculate the association, dissociation and strand displacement rates displayed by short oligonucleotides (5nt-12nt) that exhibit no expected secondary structure as simple functions of oligonucleotide length, CG content, ΔG of hybridization and ΔG of toehold binding. We then show that the resultant calculated kinetic parameters are consistent with the experimentally observed time dependent changes in concentrations of the different species present in mixtures of multiple competing RNA strands. We show that by changing the mixture composition, it is possible to create and tune kinetic traps that extend by orders of magnitude the typical sub-second hybridization timescale of two complementary oligonucleotides. We suggest that the slow equilibration of complex oligonucleotide mixtures may have facilitated the nonenzymatic replication of RNA during the origin of life., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: It is debated whether external anal sphincter (EAS) electromyography can distinguish between multiple system atrophy (MSA) and Parkinson's disease (PD), whereas its usefulness for MSA prognosis is unknown., Objectives: We explored the diagnostic and prognostic value and clinical correlations of EAS electromyography patterns in MSA., Methods: We collected clinical data and EAS electromyography findings in 72 patients with MSA and 21 with PD., Results: We identified four EAS patterns. The normal pattern was frequently observed in PD and associated with prolonged survival when identified in MSA. Abnormal patterns were predominant in MSA. The most severe pattern was associated with the highest likelihood of MSA diagnosis and with the worst prognosis in the MSA cohort. MSA patients with EAS abnormalities often showed urogenital symptoms and fecal incontinence., Conclusions: The increasing severity of EAS electromyography patterns paralleled diagnostic accuracy and survival in MSA, and correlated with prevalence of bladder and bowel symptoms. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Although various motor manifestations can be seen in patients with cerebrospinal fluid (CSF) disorders, such as hydrocephalus or intracranial hypotension, the clinical presentation with parkinsonism is not clearly elucidated., Methods: We searched the literature for studies describing the occurrence of parkinsonism in subjects with normal pressure hydrocephalus (NPH), obstructive hydrocephalus, and intracranial hypotension. We analyzed the clinical presentation (particularly with respect to bradykinesia, rigidity, rest tremor, and gait disturbance/postural instability) as well as the response to treatment., Results: Parkinsonism was most commonly reported in NPH patients. Although gait disturbance/postural instability is a well-known motor symptom of NPH, other cardinal signs include upper limb involvement or asymmetric presentation. As for obstructive hydrocephalus, parkinsonism was mainly observed in subjects with aqueductal stenosis and more often after shunt surgery. Patients with NPH or obstructive hydrocephalus rarely improved with levodopa therapy, while most subjects only improved with shunt surgery. Although the mechanism is still controversial, a functional involvement of nigrostriatal pathway has been hypothesized based on imaging studies and case reports. Brain imaging is also helpful for atypical cases of intracranial hypotension presenting with parkinsonism. Parkinsonism improved after treatment in such cases as well., Conclusions: Studies exploring the relationship between CSF disorders and parkinsonism are mainly descriptive and their quality is generally poor. However, considering that these disorders can be treated, clinicians' awareness of the differential diagnosis is important and future studies better exploring the underlying pathophysiological mechanisms are warranted. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Noninvasive brain stimulation techniques can be used to study in vivo the changes of cortical activity and plasticity in subjects with Parkinson's disease (PD). Also, an increasing number of studies have suggested a potential therapeutic effect of these techniques. High-frequency repetitive transcranial magnetic stimulation (rTMS) and anodal transcranial direct current stimulation (tDCS) represent the most used stimulation paradigms to treat motor and nonmotor symptoms of PD. Both techniques can enhance cortical activity, compensating for its reduction related to subcortical dysfunction in PD. However, the use of suboptimal stimulation parameters can lead to therapeutic failure. Clinical studies are warranted to clarify in PD the additional effects of these stimulation techniques on pharmacologic and neurorehabilitation treatments., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Genome instability is a condition characterized by the accumulation of genetic alterations and is a hallmark of cancer cells. To uncover new genes and cellular pathways affecting endogenous DNA damage and genome integrity, we exploited a Synthetic Genetic Array (SGA)-based screen in yeast. Among the positive genes, we identified VID22, reported to be involved in DNA double-strand break repair. vid22Δ cells exhibit increased levels of endogenous DNA damage, chronic DNA damage response activation and accumulate DNA aberrations in sequences displaying high probabilities of forming G-quadruplexes (G4-DNA). If not resolved, these DNA secondary structures can block the progression of both DNA and RNA polymerases and correlate with chromosome fragile sites. Vid22 binds to and protects DNA at G4-containing regions both in vitro and in vivo. Loss of VID22 causes an increase in gross chromosomal rearrangement (GCR) events dependent on G-quadruplex forming sequences. Moreover, the absence of Vid22 causes defects in the correct maintenance of G4-DNA rich elements, such as telomeres and mtDNA, and hypersensitivity to the G4-stabilizing ligand TMPyP4. We thus propose that Vid22 is directly involved in genome integrity maintenance as a novel regulator of G4 metabolism., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

(1) Background: Sprengel's deformity (SD) is a rare congenital anomaly caused by failure in the descent of the scapula. We aimed to systematically review the current literature reporting data from children undergoing surgery for SD, in order to explore the rate of success and complications of the different surgical techniques, possibly providing recommendations about the management of SD in children. (2) Methods: we electronically searched the literature from Ovid, MEDLINE and the Cochrane Library databases. Demographic data, surgical procedures, outcomes and complications were analyzed. We categorized surgical procedures into five groups. (3) Results: 41 articles met the inclusion criteria, showing a poor overall study quality; 674 patients (711 shoulders) were analyzed. Green's and Woodward's procedures, both aiming the scapular relocation in a more anatomical position, were the most commonly used techniques. We counted 168 adverse events (18 major complications). The best clinical and cosmetic results seem to be achieved when surgery is performed in children aged less than eight years. (4) Conclusions: this paper represents the first systematic review reporting qualitative and quantitative data about the surgical treatment of SD. Surgery for SD seems to be effective in increasing the shoulder's range of motion and improving the cosmetic appearance in almost all cases, with a low rate of major complications.

Background and Purpose: Neuropathological studies can elucidate the mechanisms of nervous system damage associated with SARS-CoV-2 infection. Despite literature on this topic is rapidly expanding, correlations between neurological symptoms and brain pathology findings in COVID-19 patients remain largely unknown., Methods: We performed a systematic literature review on neuropathological studies in COVID-19, including 438 patients from 45 articles published by April 22, 2021. We retrieved quantitative data regarding demographic, clinical, and neuropathological findings. We carried out a Wilcoxon rank sum test or χ 2 test to compare patients' subgroups based on different clinical and brain pathology features., Results: Neuropathological findings in COVID-19 patients were microgliosis (52.5%), astrogliosis (45.6%), inflammatory infiltrates (44.0%), hypoxic-ischemic lesions (40.8%), edema (25.3%), and hemorrhagic lesions (20.5%). SARS-CoV-2 RNA and proteins were identified in brain specimens of 41.9% and 28.3% of subjects, respectively. Detailed clinical information was available from 245 patients (55.9%), and among them, 96 subjects (39.2%) had presented with neurological symptoms in association with typical COVID-19 manifestations. We found that: (i) the detection rate of SARS-CoV-2 RNA and proteins in brain specimens did not differ between patients with versus those without neurological symptoms; (ii) brain edema, hypoxic-ischemic lesions, and inflammatory infiltrates were more frequent in subjects with neurological impairment; (iii) neurological symptoms were more common among older individuals., Conclusions: Our systematic revision of clinical correlates in COVID-19 highlights the pathogenic relevance of brain inflammatory reaction and hypoxic-ischemic damage rather than neuronal viral load. This analysis indicates that a more focused study design is needed, especially in the perspective of potential therapeutic trials., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Matrix metalloproteinases (MMPs) are a heterogeneous family of endopeptidases that play a role in many physiological functions, including the immune response. An imbalance between the activity of MMPs and their physiological tissue inhibitors (TIMPs) has been proposed in the pathophysiology of different autoimmune disorders. We aimed to assess the plasmatic levels of MMP-2, MMP-9, and their inhibitors TIMP-1 and -2 in patients with chronic inflammatory demyelinating polyneuropathy (CIDP)., Subjects and Methods: Twenty patients with CIDP and 20 age- and sex-matched healthy controls were enrolled. Plasma concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined by the enzyme-linked immunosorbent assay., Results: CIDP subjects had higher MMP-9 concentrations along with TIMP-1 downregulation when compared to controls, with the consequent increase in the MMP-9/TIMP-1 ratio (p<0.000002 for all measures). Conversely, the concentration of MMP-2 was lower in the CIDP group (p<0.01) without changes in the TIMP-2 concentration. The MMP-2/TIMP-2 ratio was decreased in the patients' group (p<0.02)., Discussion: We provide first preliminary evidence that the plasmatic pattern of MMPs and TIMPs is markedly altered in patients with CIDP. Future studies are needed to assess the potential usefulness of these new biomarkers in the clinical setting., (© 2021. Fondazione Società Italiana di Neurologia.)

Objective: To determine changes in clinical features and striatal dopamine reuptake transporter (DAT) density after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH)., Methods: Participants with probable iNPH were assessed at baseline by means of clinical rating scales, brain MRI, and SPECT with [ 123 I]-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT). Levodopa responsiveness was also evaluated. Patients who did or did not undergo lumboperitoneal shunt were clinically followed up and repeated SPECT after 2 years., Results: We enrolled 115 patients with iNPH. Of 102 patients without significant levodopa response and no signs of atypical parkinsonism, 92 underwent FP-CIT SPECT (58 also at follow-up) and 59 underwent surgery. We identified a disequilibrium subtype (phenotype 1) and a locomotor subtype (phenotype 2) of higher-level gait disorder. Gait impairment correlated with caudate DAT density in both phenotypes, whereas parkinsonian signs correlated with putamen and caudate DAT binding in patients with phenotype 2, who showed more severe symptoms and lower striatal DAT density. Gait and caudate DAT binding improved in both phenotypes after surgery ( p < 0.01). Parkinsonism and putamen DAT density improved in shunted patients with phenotype 2 ( p < 0.001). Conversely, gait, parkinsonian signs, and striatal DAT binding worsened in patients who declined surgery ( p < 0.01)., Conclusions: This prospective interventional study highlights the pathophysiologic relevance of striatal dopaminergic dysfunction in the motor phenotypic expression of iNPH. Absence of levodopa responsiveness, shunt-responsive parkinsonism, and postsurgery improvement of striatal DAT density are findings that corroborate the notion of a reversible striatal dysfunction in a subset of patients with iNPH., (© 2021 American Academy of Neurology.)

Background: The clinical spectrum of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, may be quite wide, including neurological symptoms. Among them, para-infectious or post-infectious neurological syndromes (PINS), caused by an inflammatory response against the central and/or peripheral nervous system, have been reported. The aim of this paper is to illustrate the functional and neurophysiological recovery in a series of subjects with COVID-19-related PINS who underwent intensive neurorehabilitation. Materials and Methods: Five patients with PINS associated with COVID-19 were evaluated at baseline and followed up for 6 months. Three of them had polyradiculoneuropathy and two patients had myelitis. The onset of the neurological syndromes was temporally associated with the SARS-CoV-2 infection. After completing the acute neurological treatments in the intensive care unit, patients underwent a personalized multidisciplinary rehabilitation program. An in-depth clinical, functional, and electrophysiological assessment was carried out at baseline and at 3- and 6-month follow-ups. Results: Among patients with polyradiculoneuropathy, the electrophysiological evaluation at baseline disclosed an acute inflammatory demyelinating polyradiculoneuropathy (AIDP) in two patients and an acute motor and sensory axonal neuropathy (AMSAN) in the third patient. At follow-up, the electrophysiological features improved in one subject with AIDP and were stable in the remaining two cases. The functional assessment after neurorehabilitation showed global recovery and full independence in walking and in activities of daily life in one patient and mild improvement in the other two cases. Of the two subjects with myelitis, the baseline electrophysiological examination showed a prolonged central motor conduction time, which returned to normal in one patient, whereas it improved but remained pathological in the other patient at follow-up. The neurorehabilitation led to a substantial functional improvement in both subjects. Discussion and Conclusions: This is the first study to describe clinical and electrophysiological aspects along with medium-term outcome in patients with COVID-19-related neurological manifestations who underwent an intensive rehabilitation program. The functional outcome following neurorehabilitation in patients with PINS related to SARS-CoV-2 infection is variable. In our small case series, subjects with polyradiculoneuropathy had a poorer recovery compared to patients with myelitis. The clinical course largely paralleled the follow-up electrophysiological findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship, with one of the authors with several of the authors CT, GC, DM, MT, EA, and MA., (Copyright © 2021 Avenali, Martinelli, Todisco, Canavero, Valentino, Micieli, Alfonsi, Tassorelli and Cosentino.)

Background: Idiopathic normal pressure hydrocephalus can present with parkinsonism. However, abnormalities of the striatal dopamine reuptake transporter are unclear., Objectives: To explore presence and features of striatal dopaminergic deficit in subjects with idiopathic normal pressure hydrocephalus as compared to Parkinson's disease (PD) patients and healthy controls., Methods: We investigated 50 subjects with idiopathic normal pressure hydrocephalus, 25 with PD, and 40 healthy controls. All participants underwent [ 123 I]-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane and single-photon emission computed tomography to quantify the striatal dopamine reuptake transporter binding. All subjects with idiopathic normal pressure hydrocephalus underwent a levodopa (l-dopa) challenge test and magnetic resonance imaging to evaluate ventriculomegaly and white matter changes. Gait, cognition, balance, and continence were assessed with the Idiopathic Normal Pressure Hydrocephalus Rating Scale, and parkinsonism with the motor section of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale. All patients completed a 2-year follow-up., Results: A total of 62% of patients with idiopathic normal pressure hydrocephalus featured a reduced striatal dopamine reuptake transporter binding, which correlated with the severity of parkinsonism but not with features of ventriculomegaly or white matter changes. Unlike PD, this dopaminergic deficit in idiopathic normal pressure hydrocephalus was more symmetric and prominent in the caudate nucleus., Conclusions: Subjects with idiopathic normal pressure hydrocephalus can present a reduction of striatal dopamine reuptake transporter binding, which is consistent with the severity of parkinsonism and qualitatively differs from that found in PD patients. Longitudinal interventional studies are needed to prove a role for striatal dopamine reuptake transporter deficit in the pathophysiology of idiopathic normal pressure hydrocephalus. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)

Idiopathic normal pressure hydrocephalus (iNPH) is a common neurological disorder with unknown etiology. A selective depletion of aquaporin 4 (AQP4) has been shown in iNPH patients. We collected serum and cerebrospinal fluid (CSF) from 43 iNPH patients and 35 with other neurodegenerative conditions, and serum from 43 healthy subjects. All samples were tested for AQP4-IgG/IgA/IgM antibodies using a live cell-based assay. No patients or controls had serum/CSF AQP4-IgG/IgA. One/43 iNPH patient and 0/43 controls tested positive for serum AQP4-IgM. The AQP4-IgM-positive iNPH patient had no clinico-radiological distinctive features. AQP4 antibodies are unlikely to play a role in iNPH pathogenesis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To investigate reproducibility and reaction time of oropharyngeal swallowing in patients with Parkinson's disease (PD) and atypical parkinsonisms (APs)., Methods: We enrolled 19 patients with PD, 30 with APs, and 20 healthy subjects. Presence and severity of dysphagia were assessed with clinical and fiberoptic endoscopic evaluations of swallowing. Reproducibility of the oral and pharyngeal phases of swallowing were respectively assessed by calculating the 'similarity index' of the electromyography activity of the submental/suprahyoid muscles and of the laryngeal-pharyngeal mechanogram during consecutive swallows. These were performed both 'on command' and spontaneously. The swallowing reaction time was also recorded., Results: Reproducibility of the oral phase of swallowing was reduced in patients with dysphagia, mainly when swallowing 'on command'. Swallowing reaction time was prolonged in dysphagic patients. These electrophysiological parameters did not vary among different parkinsonian syndromes and correlated with dysphagia severity., Conclusions: Increased variability of oral swallowing automatisms and abnormal sensorimotor integration may be of relevance for the pathophysiology of dysphagia in parkinsonian syndromes., Significance: The electrophysiological assessment represents a valuable tool to investigate swallowing alterations in parkinsonian syndromes. It may also provide useful insights into clinical severity and pathophysiology of dysphagia, giving clues for the choice of the best therapeutic approach., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: In this prospective, controlled, monocentric study, we described the clinical and neuroimaging 12-month follow-up of two parallel cohorts of subjects with idiopathic normal pressure hydrocephalus (iNPH), who did or did not undergo lumboperitoneal shunt (LPS)., Methods: We recruited 78 iNPH patients. At baseline, subjects underwent clinical and neuropsychological assessments, 3 T magnetic resonance imaging (MRI), and tap test. After baseline, 44 patients (LPS group) opted for LPS implantation, whereas 34 subjects (control group) declined surgery. Both cohorts were then followed up for 12 months through scheduled clinical and neuropsychological evaluations every 6 months. 3 T MRI was repeated at 12-month follow-up., Results: Gait, balance, and urinary continence improved in the LPS group, without significant influence on cognitive functions. Conversely, gait and urinary continence worsened in the control group. No preoperative MRI parameter was significant outcome predictor after LPS. Of relevance, in responders to LPS, we found postoperative reduction of periventricular white matter (PWM) hyperintensities, which were instead increased in the control group., Conclusions: LPS is safe and effective in iNPH. An early surgical treatment is desirable to prevent clinical worsening. Post-surgery decrease of PWM hyperintensities may be a useful MRI marker surrogate for clinical effectiveness of LPS.

Introduction: Myoclonus-dystonia is a rare syndrome typically occurring during childhood or adolescence, mainly due to SGCE pathogenic variants. Early-onset, atypical presentations of myoclonus-dystonia have recently been associated with KCTD17 variants. In these cases, laryngeal involvement was reported in the advanced stages., Methods: We evaluated a 52-year-old man with myoclonus-dystonia and positive family history. He underwent an electromyographic investigation of vocal cord and forearm muscles. Whole-exome sequencing was also performed., Results: Onset of symptoms was at 51 years with dysphonia and vocal tremor. Electromyography disclosed abductor spasmodic dysphonia and laryngeal myoclonus. The patient later developed writer's cramp, upper limb myoclonus, and blepharospasm. Botulinum toxin injection led to improvement of the writer's cramp and to a lesser extent of the spasmodic dysphonia. Genetic analysis identified a heterozygous missense variant in exon 2 of KCTD17: c.229 C > A (p.Leu77Ile), consistently predicted as damaging., Conclusions: We suggest that the KCTD17-associated phenotypic spectrum may include late onset (even in late adulthood) as well as early and prominent laryngeal involvement., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Dysphagia in the elderly, known as presbydysphagia, has become a relevant public health problem in several countries. Swallowing disorders may be a consequence of different neurological disorders (secondary presbydysphagia) or the expression of the aging process itself (primary presbydysphagia). We aimed to test the therapeutic potential of two different non-invasive brain stimulation (NIBS) techniques in subjects with primary or secondary presbydysphagia., Methods: A blinded randomized controlled trial with crossover design was carried out in 42 patients, randomly assigned to anodal transcranial direct current stimulation (tDCS) or intermittent theta-burst stimulation (TBS) group. Both tDCS and TBS were applied for 5 consecutive days over the right swallowing motor cortex. The swallowing function was assessed before and 1 and 3 months after the stimulation using the Dysphagia Outcome and Severity Scale (DOSS), scored based on clinical assessment and fiberoptic endoscopic evaluation of swallowing. An electrophysiological method was also applied to evaluate changes in the reproducibility of the swallowing behavior., Key Results: Both real tDCS and TBS had beneficial effects on the swallowing function in patients with primary and secondary presbydysphagia. Anodal tDCS resulted in an improvement of 0.5 points in DOSS at 1-month follow-up (P = .014), whereas intermittent TBS induced an increase of 0.7 and 0.6 points at 1- and 3-month follow-up evaluations, respectively (P = .0001 and P = .005, respectively). Reproducibility of both the oral and pharyngeal phases of swallowing significantly increased at 1-month follow-up., Conclusions and Inferences: Our results suggest that non-invasive cortical stimulation may be useful for dysphagia recovery in elderly patients., (© 2020 John Wiley & Sons Ltd.)

The initiation of gait is a highly challenging task for the balance control system, and can be used to investigate the neural control of upright posture maintenance during whole-body movement. Gait initiation is a centrally-mediated motion achieved in a principled, controlled manner, including predictive mechanisms (anticipatory postural adjustments, APA) that destabilize the antigravitary postural set of body segments for the execution of functionally-optimized stepping. Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by early impairment of balance and frequent falls. The neural correlates of postural imbalance and falls in PSP are largely unknown. We biomechanically assessed the APA at gait initiation (imbalance, unloading, and stepping phases) of 26 patients with PSP and 14 age-matched healthy controls. Fourteen of 26 enrolled patients were able to perform valid gait initiation trials. The influence of anthropometric and base-of-support measurements on the biomechanical outcome variables was assessed and removed. Biomechanical data were correlated with clinical findings and, in 11 patients, with brain metabolic abnormalities measured using positron emission tomography and 2-deoxy-2-[18F]fluoro-D-glucose. Patients with PSP showed impaired modulation of the center of pressure displacement for a proper setting of the center of mass momentum and subsequent efficient stepping. Biomechanical measurements correlated with "Limb motor" and "Gait and midline" subscores of the Progressive Supranuclear Palsy Rating Scale. Decreased regional glucose uptake in the caudate nucleus correlated with impaired APA programming. Hypometabolism of the caudate nucleus, supplementary motor area, cingulate cortex, thalamus, and midbrain was associated with specific biomechanical resultants of APA. Our findings show that postural instability at gait initiation in patients with PSP correlates with deficient APA production, and is associated with multiple and distinctive dysfunctioning of different areas of the supraspinal locomotor network. Objective biomechanical measures can help to understand fall-related pathophysiological mechanisms and to better monitor disease progression and new interventions., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by dysautonomia in combination with parkinsonian and cerebellar signs. Stridor may also occur and it is associated with life-threatening events and poor prognosis. The pathophysiology of stridor in MSA is still debated., Objective: To define correlations between diurnal electromyographic (EMG) abnormalities of vocal cord muscles and stridor in MSA phenotypes., Methods: We recruited 60 patients with "probable" MSA (45 with parkinsonian [MSA-P] and 15 with cerebellar phenotype [MSA-C]). Nocturnal stridor was detected with video-polysomnography, whereas diurnal stridor was clinically noted when present. A diurnal kinesiologic EMG study of the adductor thyroarytenoid and the abductor posterior cricoarytenoid muscles was also performed., Results: Among subjects with nocturnal stridor, MSA-P patients predominantly showed a paradoxical burst-like activation of the adductor thyroarytenoid muscle during inspiration. This dystonic pattern was associated with nocturnal stridor in MSA-P (odds ratio [OR] = 23.64, 95% confidence interval [CI] 3.42-70.77, p < 0.001). Conversely, MSA-C patients with nocturnal stridor mainly had additional neurogenic findings of vocal cord muscles. This dystonic-plus pattern correlated with nocturnal stridor in MSA-C (OR = 17.21, 95% CI 4.17-74.92, p < 0.01). The findings of diurnal stridor paralleled the observations for nocturnal stridor., Conclusions: The pathophysiology of stridor may differ between MSA phenotypes, possibly related to dysfunctional supranuclear mechanisms in MSA-P (dystonic pattern) and to additional nuclear damage in MSA-C (dystonic-plus pattern)., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Animal-assisted intervention (AAIs) represent an adequate expression of integrated medicine, according to the One Health approach. We argue that AAIs are interventions based on interspecific relationships between humans and animals. Although there are many studies on the effects of AAIs on animal and human health and wellbeing, research is still needed to give us more data. For example, information is still lacking on the aspects characterizing and influencing the interspecific relationships occurring in AAIs. The efficacy of an intervention based on interspecific relationships will be influenced by different factors, such as attachment styles and personalities of both the animal and the handler, an appropriate choice of animal species and their individuality, animal educational training techniques, the relationship between the handler and the animal, and relational reciprocity between animal, the patients, and members of the working team., Method: This article aims to contribute to the study of interspecific relationships in AAIs via theoretical considerations. An interspecific relationship determines the result of safe interventions, which directly influences the welfare of the animal. Results and considerations: AAIs should be evaluated systemically as a network within a process in which every component interacts with and influences other components. Standardized methods using appropriate tests and parameters are needed to better select appropriate animals (i.e., species and individual subjects) using interspecific relational competences as well as appropriate educational training methods and health protocols to assess potential risks.

Introduction: Idiopathic Normal Pressure Hydrocephalus (iNPH) is a complex syndrome of ventriculomegaly that can include parkinsonian-like features besides the classical triad of cognitive decline, urinary incontinence, and gait/balance disturbances. Pisa syndrome (PS) is a postural abnormality often associated with parkinsonism and defined as lateral trunk flexion greater than 10° while standing that resolves in the supine position. We reported a case series of classical "fixed" PS and one case of "Metronome" recurrent side-alternating PS in iNPH, displaying opposite electromyographic patterns of paraspinal muscles., Methods: Eighty-five iNPH patients were followed longitudinally for at least one year through scheduled clinical and neuropsychological visits., Results: Five (5.9%) subjects revealed PS. None of them had nigrostriatal dopaminergic involvement detected by [123I]FP-CIT SPECT. Among these patients, four had "fixed" PS, whereas one showed a recurrent side-alternating PS which repeatedly improved after ventriculo-peritoneal shunt and following adjustments of the valve-opening pressure of the shunt system., Discussion: This is the first case series of PS in iNPH and the first report of "Metronome" PS in iNPH. The prompt response of the abnormal trunk postures through cerebrospinal fluid (CSF) shunt surgery suggests a causative role of an altered CSF dynamics. PS and gait disorders in iNPH could be explained by a direct involvement of cortico-subcortical pathways and subsequent secondary brainstem involvement, with also a possible direct functional damage of the basal ganglia at the postsynaptic level, due to enlargement of the ventricular system and impaired CSF dynamics. The early detection of these cases supports a proper surgical management., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: In the past 10 years, long-term studies have demonstrated that guided bone regeneration (GBR) is a successful and reliable technique for vertical and horizontal ridge augmentation, but strict and rigorous protocols must be adopted., Material and Methods: Because no reports have yet been published with statements and clinical recommendations for GBR, a closed meeting of all authors was organized to discuss this matter during a GBR symposium held in Bologna (Italy) in October 2016. The authors focused on the findings of systematic and narrative reviews, prepared before the meeting, covering aspects of the clinical management of GBR techniques. Successively, a discussion based on the scientific evidence and on the experts' opinions led to the formulation of statements, clinical recommendations, and implications for future research., Results: To avoid complications and to optimize outcomes, the following factors should be considered by clinicians: patient selection; analysis of defect type; blood supply; antibiotic treatment; flap passivation; delayed implant placement; combination of autogenous bone and xenograft or allograft; rigorous fixation of membranes; removal after 6 to 9 months; analysis of complications; soft-tissue management; and high care in scarred sites and in esthetic areas., Conclusions: The present consensus report reviewed the scientific evidence and provided specific guidelines and recommendations for clinical practice and the different approaches to GBR techniques to ensure surgical success and predictable outcomes.

Purpose: The purpose of this study was to evaluate the role of keratinised mucosa on the long-term success of dental implants., Materials and Methods: Thirty-two edentulous patients had one of their dental arches rehabilitated with a provisional screw-retained resin reinforced cross-arch fixed prosthesis supported by four immediately loaded implants. The two central straight implants were randomly allocated in two equal groups, according to a parallel-group design, to receive or not intermediate abutments (Multi-Unit Abutment, MUA). However, for the purpose of the present publication, the study was considered as a prospective single cohort study. To be immediately loaded, implants had to be inserted with a minimum torque of 30 Ncm, which was achieved by all implants. Provisional prostheses were delivered within 24 hours and were replaced, after 4 months, by definitive screw-retained metal-ceramic prostheses. Patients were followed up to 5 years after loading. Prostheses were removed every 8 months to facilitate professionally delivered maintenance. Outcome measures were prosthesis and implant failures, complications, peri-implant marginal bone level (MBL) changes, bleeding on probing (BoP) and keratinised mucosa height (KMH). The absence of vestibular or lingual keratinised mucosa was put in relation with peri-implant bone loss and BoP., Results: Five-years after loading two patients dropped out and no implant or prosthetic failure occurred. Four patients were affected by prosthetic complications. At delivery of definitive prostheses, 32 (25%) implants had at least one vestibular or lingual site with no KMH and 96 (75%) implants had both sites with some KMH. Multi-level models did not show any statistically significant association between KMH at the time of delivery of the definitive prosthesis and changes in MBL and BoP at 5 years (estimate = 0.02; 95% CI: -0.02 to 0.05; P = 0.3393; and 1.02; 95% CI: 0.79 to 1.33; P = 0.8695, respectively). When KMH was analysed as dichotomous variable, implants with presence of KMH at delivery of definitive prosthesis at both vestibular and lingual aspects showed a trend of less BoP (estimate = -0.8; 95% CI: -1.69 to 0.08; P = 0.0741) but a statistically significant greater MBL loss compared to implants where KMH was only present at one site (estimate = 0.18; 95% CI: -0.1 to 0.3; P = 0.0041)., Conclusions: The 5-year after loading outcome of immediately loaded screw-retained cross-arch prostheses supported by four implants is excellent in both the maxilla and mandible. Although the height of the keratinised mucosa did not seem to alter the clinical outcomes, its presence both at vestibular and lingual sites was associated with an increased marginal bone loss when compared to implants having at least one side without keratinised mucosa., Competing Interests: Conflict of interest statement: This study was completely self-funded and the authors declare not to have any conflict of interest.

Self-synthesizing materials, in which supramolecular structuring enhances the formation of new molecules that participate to the process, represent an intriguing notion to account for the first appearance of biomolecules in an abiotic Earth. We present here a study of the abiotic formation of interchain phosphodiester bonds in solutions of short RNA oligomers in various states of supramolecular arrangement and their reaction kinetics. We found a spectrum of conditions in which RNA oligomers self-assemble and phase separate into highly concentrated ordered fluid liquid crystal (LC) microdomains. We show that such supramolecular state provides a template guiding their ligation into hundred-bases long chains. The quantitative analysis presented here demonstrates that nucleic acid LC boosts the rate of end-to-end ligation and suppresses the formation of the otherwise dominant cyclic oligomers. These results strengthen the concept of supramolecular ordering as an efficient pathway toward the emergence of the RNA World in the primordial Earth.

We demonstrate that nucleic acid (NA) mononucleotide triphosphates (dNTPs and rNTPs), at sufficiently high concentration and low temperature in aqueous solution, can exhibit a phase transition in which chromonic columnar liquid crystal ordering spontaneously appears. Remarkably, this polymer-free state exhibits, in a self-assembly of NA monomers, the key structural elements of biological nucleic acids, including: long-ranged duplex stacking of base pairs, complementarity-dependent partitioning of molecules, and Watson-Crick selectivity, such that, among all solutions of adenosine, cytosine, guanine, and thymine NTPs and their binary mixtures, duplex columnar ordering is most stable in the A-T and C-G combinations., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Objective : To evaluate therapeutic potential of different montages of transcranial direct current stimulation (tDCS) in Parkinson's Disease (PD) patients with asymmetric motor symptoms. Materials and Methods : Fourteen patients with asymmetric PD underwent, while on treatment, seven separate sessions including electrophysiological and clinical evaluation at baseline and after anodal, cathodal and sham tDCS of the primary motor cortex (M1) of the two hemispheres. Changes in motor cortical excitability were evaluated by transcranial magnetic stimulation (TMS). Effects on motor symptoms were assessed by testing finger tapping (FT) and upper limb bradykinesia, and by using the Italian validated Movement Disorder Society revision of the Unified PD Rating Scale (MDS-UPDRS). Results : Only anodal tDCS of the more-affected M1 (contralateral to the more-affected body side) and cathodal tDCS of the less-affected M1 (contralateral to the less-affected body side) were able to induce significant changes in cortical excitability, i.e., facilitation and inhibition of the motor evoked potentials respectively. The motor performances of both hands significantly improved after anodal tDCS of the more-affected M1, as well as after cathodal tDCS of the less-affected one. Conclusion : Our findings support the potential usefulness of tDCS as add-on treatment for asymmetric PD, also providing interesting clues on the possible pathophysiological role played by an asymmetric activation of homologous motor cortical areas in PD.

Background and Aims: Neurogenic dysphagia linked to failed relaxation of the upper esophageal sphincter (UES) can be treated by injecting botulinum toxin (BTX) into the cricopharyngeal (CP) muscle. We compared the effects of this treatment in different neurological disorders with dysphagia, to evaluate its efficacy over time including the response to a second injection. Materials and Methods: Sixty-seven patients with neurogenic dysphagia associated with incomplete or absent opening of the UES (24 with brainstem or hemispheric stroke, 21 with parkinsonian syndromes, 12 with multiple sclerosis, and 10 with spastic-dystonic syndromes secondary to post-traumatic encephalopathy) were treated with the injection of IncobotulinumtoxinA (dose 15-20 U) into the CP muscle under electromyographic guidance. The patients were assessed at baseline and after the first and second treatment through clinical evaluation and fiberoptic endoscopy of swallowing, while their dysphagia was quantified using the Dysphagia Outcome and Severity Scale (DOSS). An electrokinesiographic/electromyographic study of swallowing was performed at baseline. Results : Most patients responded to the first BTX treatment: 35 patients (52.2%) were classified as high responders (DOSS score increase >2 levels), while other 19 patients (28.4%) were low responders (DOSS score increase of ≤2 levels). The effect of the first treatment usually lasted longer than 4 months (67%), and in some cases up to a year. The treatment efficacy remained high also after the second injection: 31 patients (46.3%) qualified as high responders and other 22 patients (32.8%) showed a low response. Only in the parkinsonian syndromes group we observed a reduction in the percentage of high responders as compared with the first treatment. Side effects were mostly mild and reported in non-responders following the first injection. A severe side effect, consisting of ingestion pneumonia, was observed following the second BTX injection in two patients who had both been non-responders to the first. Non-responders were characterized electromyographically by higher values of the oropharyngeal interval. Conclusion: These findings confirm the effectiveness of IncobotulinumtoxinA injection in the treatment of neurogenic dysphagia due to hyperactivity and relaxation failure of the UES. Caution should be used as regards, the re-injection in non-responders to the first treatment.

Objectives: To monitor the results of ultrasound (US)-guided percutaneous treatment of calcific tendinopathy of the shoulder at 12 months (T12) after treatment (T0). To verify the possible relations between some pre- and post-procedural variables with the clinical outcome at T12., Methods: Forty-seven patients (26 female and 21 male) were enrolled in the study. Patients' approval and written informed consent were obtained. Symptoms were assessed by Constant Shoulder Score (CSS) at T0 and T12. Thirty of these also underwent a CSS control at 3 months (T3). The treatment efficacy was statistically tested for relation with location and type of calcification, characteristics of the tendon and subdeltoid bursa, impingement, and rehabilitation treatments., Results: There was a significant increase in the average CSS value between T0 and T12 (40.7 vs. 75.3). The variables analysed did not show a statistically significant effect on the outcome at T12. A link was noticed only between patients' increasing age and score improvement, particularly among female subjects., Conclusion: US-guided treatment of calcific tendonitis is a viable therapeutic option. No pre- or intra-procedural parameters emerged which might help in predicting the outcome, apart from patients' needs in everyday life., Key Points: • US-guided tcreatment of shoulder calcific tendinopathy is an excellent therapeutic option • Long-term results seem greatly affected by patients' features and needs in everyday life • No proven pre- or intra-procedural parameters emerged that might predict the outcome.

The aim of this prospective, randomized, controlled, multicenter study was to evaluate and compare the histologic and histomorphometric aspects of extraction sockets grafted with two commercially available bovine bone xenografts: Endobon (test group) and Bio-Oss (control group). The study was designed to ensure that baseline variables between groups were as similar as possible to allow for a direct comparison of graft healing characteristics. Thirty-eight patients contributed 62 augmented extraction sites to the study. All sites were grafted with one type of bovine bone mineral and covered with a resorbable collagen membrane for 6 months of healing prior to implant placement surgery. The histologic outcomes between the two treatment groups are similar, with de novo bone (mean ± SD) for the test group at 28.5% ± 20% and for the control group, 31.4% ± 18%. Histologic specimens also include membrane remnants. All but two implants integrated successfully after 1 year of follow-up. This investigation provides support for the efficacy of bovine bone xenograft for socket preservation when subsequent implant placement is planned.

The aim of this study was to evaluate histologically and biomechanically the peri-implant bone healing around implants placed with high torque after a follow-up of 8 and 12 weeks. A total of 12 implants were placed in the lower edge of the mandible of 2 sheep. In each sheep, 3 implants were placed with a low torque (<25 N · cm, LT group) as a control, and 3 implants were placed with a high insertion torque (maximum torque, HT group). The sheep were killed after 8 and 12 weeks of healing, and the implants were examined for removal torque, resonance frequency analysis, and histologic analysis.The mean insertion torque in the LT group was 24 N · cm, whereas it was 105.6 N · cm in HT. All the implants osseointegrated and histologic analysis showed similar aspects of the peri-implant bone tissue for both groups and both healing times. Mean removal torque values for LT implants were 159.5 and 131.5 N · cm after 8 and 12 weeks, respectively, whereas those for the HT were 140 and 120 N · cm at 8 and 12 weeks, respectively. Implant stability quotient values were 26.6 and 76 for the LT group and 74 and 76 for the HT group at 8 and 12 weeks, respectively.It could be concluded that high implant insertion torque does not induce adverse reaction in cortical bone and does not lead to implant failure.

Purpose: The purpose of this study was to analyze, in an animal model, the histologic and biomechanical phenomena at the bone-implant interface of implants inserted with high torque (HT) as compared to low torque (LT) during the first 6 weeks of healing., Materials and Methods: Forty tapered-screw-form implants were placed in five hybrid sheep. The implant sites were placed in the mandible, using an extraoral approach; four were placed with HT (test: mean 110 Ncm) on one side and four were placed with LT (control: mean 10 Ncm) on the contralateral side. After 1, 2, 3, 4, and 6 weeks of healing, removal torque testing and resonance frequency analysis were performed and the animals were sacrificed for histologic examination., Results: Implants from the HT group showed significantly higher bone apposition than implants from the LT group at all examined healing times. Similarly, removal torque was consistently higher for the HT as compared to the LT group. A significant loss of primary stability in the HT group was evident 7 days after placement. Implants from the LT group achieved a significant increase in stability after 4 weeks. Resonance frequency analysis was unable to detect these histologic and biomechanical modifications of the bone-implant complex., Conclusions: The results of the study showed that high implant insertion torque in dense cortical bone does not induce bone necrosis or implant failure, but it does increase the primary stability of implants, which is extremely important in immediate loading protocols.

Purpose: To evaluate the efficacy of prophylactic antibiotics for dental implant placement., Materials and Methods: Thirteen dentists working in private practices agreed to participate in this trial, each centre providing 50 patients. One hour prior to implant placement, patients were randomised to take orally 2 g amoxicillin or identical placebo tablets. Patients needing bone augmentation at implant placement were not included. Outcome measures were prosthesis and implant failures, adverse events and post-operative complications. Patients were seen 1 week, 2 weeks and 4 months post-operatively., Results: Two centres did not deliver any data, two centres did not manage to include the agreed quota of patients and three patients had to be excluded. Two-hundred and fifty-two patients were evaluated in the antibiotic group and 254 in the placebo group, and none dropped out at 4 months. Four prostheses and seven implants (in five patients) failed in the antibiotics group versus 10 prostheses and 13 implants (in 12 patients) in the placebo group. Eleven complications were reported in the antibiotic group versus 13 (in 12 patients) in the placebo group. No side effects were reported. There were no statistically significant differences for prosthesis failures, implant losses and complications. Patients receiving immediate post-extractive implants had an increased failure risk compared with patients receiving delayed implants (9% versus 2%)., Conclusions: No statistically significant differences were observed, although trends clearly favoured the antibiotic group. Immediate post-extractive implants were more likely to fail.

Conflict of Interest: All materials used in this study were purchased by the author and it is therefore free of any commercial or institutional interest., Purpose: To evaluate the success rate 1 year after loading of early loaded implants placed in vertically augmented bone using deproteinised bovine bone (Bio-Oss) and a titanium-reinforced membrane (Gore-Tex)., Materials and Methods: Twenty patients provided 25 sites that were treated with vertical guided tissue regeneration (GBR) using Bio-Oss and expanded polytetrafluoroethylene titanium-reinforced membranes. After 1 year of healing, the membranes were removed and 64 implants were placed (baseline) and loaded 30 days later. Standardised periapical radiographs were obtained at baseline and 1 year thereafter. One independent assessor clinically evaluated the amount of tissue regenerated and peri-implant bone level based on the radiographs. Outcome measures were prosthesis success, implant success, complications, amount of vertically regenerated bone, peri-implant marginal bone levels and histology., Results: No patient dropped out. A total of 23 out of 25 sites healed uneventfully. Two sites showed early membrane exposure. In these sites, the surgery was repeated with success 2 months later. Clinical evaluation showed a mean vertical bone defect of 5.6 mm (SD 1.7). Mean vertical bone gain after GBR was 5.2 mm (SD 1.5). The histology of five samples retrieved from four patients showed a total percentage of xenograft and new bone of 52.6%, with dispersed graft particles surrounded by layers of bone. All implants were stable after 1 year of function, yielding a survival rate of 100%. Statistically significant peri-implant bone loss (0.95 mm; SD 0.21; 95% confidence interval 0.85 to 1.05; P < 0.001) was observed radiographically from baseline to the 1-year follow-up., Conclusions: This prospective cohort study shows that by using deproteinised bovine bone and a non-resorbable titanium-reinforced membrane, vertical bone gain can be obtained and implants can be loaded after 30 days. The vertical regenerated tissue exhibited good stability over 1 year of implant function.

The usual, initial therapy of patients with chronic lymphocytic leukemia (CLL) involves alkylating agents, corticosteroids, purine analogs, and monoclonal antibodies. The combination of these agents may lead to high complete and overall response rates, but all patients inevitably relapse, and median progression-free survival varies between 16 and 48 months. Further, these treatments present the risk of myelosuppression and infection, so that some of the combination regimens require antibiotic, antiviral, and antimycotic prophylaxis during and after their administration. We treated 4 patients with previously untreated progressive stage I Rai CCL, with a combination of cyclophosphamide, somatostatin, bromocriptine, retinoids, melatonin, and ACTH. All the patients had partial remission after 2 months and continued treatment, which was gradually reduced if lymphocyte count fell below 4000/microL. No patients had disease recurrence, and progression-free survival has not yet been reached (125, 121, 73, and 21 months, respectively). Toxicity was absent, and patients underwent the treatment at home, while carrying out their normal activities.

Purpose: To evaluate the efficacy of prophylactic antibiotics for dental implant placement., Materials and Methods: Twelve Italian private practices agreed to participate in this trial, each centre providing 30 patients. One hour prior to implant placement, patients were randomised, for consumption orally of 2 g amoxicillin or identical placebo tablets. Patients needing bone augmentation procedures were not included. Outcome measures were prosthesis and implant failures, adverse events and post-operative biological complications. Patients were seen 1 week, 2 weeks and 4 months post-operatively., Results: One centre did not deliver any data and 14 patients had to be excluded from the trial for various reasons. One hundred and fifty-eight patients were evaluated in each group and none dropped out at 4 months. Two prostheses and two implants failed in the antibiotics group, compared with four prostheses and nine implants in the placebo group. There were no statistically significant differences for prosthesis failures, implant losses, complications and side effects., Conclusions: No statistically significant differences were observed. However, four times more patients in the placebo group experienced implant failures than in the antibiotic group, and this requires further investigation.

This study investigated the bone-to-implant contact (BIC) and osteoconductive capacity (OC) of 6 different implant surfaces after early loading in humans. Two implants with different surfaces were placed side-by-side in the grafted (n= 5) and nongrafted (n = 1) sinuses of 3 volunteers. Single-tooth restorations were delivered 60 days later. After 6 months of full occlusal loading, implants were retrieved in block sections for histomorphometric analysis. One implant (acid etched) placed in grafted bone failed when loaded. There were no other complications. In grafted bone, the microtextured surface achieved the highest BIC value (94.08%), followed by the oxidized (77.32%), hydroxyapatite (HA) (74.51%), sandblasted and acid-etched (51.85%), and titanium plasma-sprayed (TPS) (41.48%) surfaces. In native bone, the acid-etched surface achieved a higher BIC value (69.03%) than the HA surface (59.03%). The highest OC value in grafted bone was exhibited by the microtextured surface (34.31%), followed by the HA (28.62%), sandblasted and acid-etched (25.08%), oxidized (17.55%), and TPS (-20.47%) surfaces. The HA surface exhibited a higher OC value (30.39%) in native bone compared with the acid-etched surface (24.0%). As a whole, highest BIC and OC values were exhibited by the microtextured surface, and lowest values were exhibited by the TPS surface. All other surfaces demonstrated excellent BIC (>50%) but varied in OC (range = 17.55%-28.62%). These findings are tempered by the limited scope and sample size of the study and should be considered preliminary. More research is needed to determine the impact of implant surface texture on BIC and OC.

The goal of this study was to histologically document the effect of two different implant surfaces on the percentage of bone-to-implant apposition achieved with implants placed in human sinus grafts. The influences of implant site and post-grafting delay time were also examined. Nine healthy volunteers were scheduled to undergo posterior maxillary sinus floor augmentation in preparation for delayed implant placement. In addition to the conventional dental implants selected for each case, titanium alloy experimental implants, 2.5 mm in diameter and 8 mm in length, were custom manufactured. Each microimplant was prepared longitudinally with two different surface topographies: machined on one side and MTX microtextured on the other side. A notch prepared across the superior aspect of the implants facilitated placement and provided a reference line between the two surfaces. Patients were divided into two groups that received the experimental microimplants at the time of conventional implant placement: Group A (six patients) received the experimental microimplants in the regenerated lateral wall of the sinus graft 11 months after graft placement, and group B (three patients) received them in the alveolar crest 6 months after graft placement. After 6 months of submerged healing, all experimental and conventional implants appeared to be clinically osseointegrated. Histologic analysis revealed that the mean bone-to-implant apposition was significantly greater with MTX (72.31% +/- 17.76%) compared to machined surfaces (38.01% +/- 19.32%), regardless of bone quality. The healing time between graft and implant placement and implant location did not statistically impact the percentage of bone-to-implant apposition.

Purpose: Somatostatin, prolactin, retinoids, melatonin and ACTH have been shown to influence the lymphatic growth, and the action of the cyclophosphamide in lymphoproliferative disorders is well known. This provided the rationale to conduct, in patients with low-grade non-Hodgkin's lymphomas (NHL), a phase II trial of a combined association of cyclophosphamide, somatostatin, bromocriptin, retinoids, melatonin and ACTH., Patients and Methods: Twenty patients with a diagnosis of low-grade NHL, stage III or IV, were included in this study. Patients received for one month the following treatment: cyclophosphamide, somatostatin, bromocriptin, retinoids, melatonin, and ACTH. The therapy was continued for two additional months in patients with stable or responding disease. After three months, the responding patients continued the therapy for three months and more., Results: Twenty patients were assessable for toxicity and response; 70% (14 of 20 patients; 95% confidence interval [CI], 50% to 90%) had a partial response; 20% (4 of 20) had stable disease, and 10% (2 of 20) progressed on therapy. Going on with the treatment, none of the 14 patients with partial response had a disease progression (average follow-up time of 21 months, range, 7 to 25), and 50% of these patients had a complete response; among 4 patients with stable disease, 25% (1 of 4) had a partial response and 75% (3 of 4) progressed on therapy (mean time to progression [TTP] 14.3 months, range, 7 to 21). The toxicity was very mild, the most common side effects being drowsiness, diarrhea and hyperglycemia., Conclusions: The association of cyclophosphamide, somatostatin, bromocriptin, retinoids, melatonin, and ACTH is well tolerated and effective in treatment of low-grade NHL at advanced stage.

Pretreatment lateral skull radiographs were studied to analyze the characteristics of facial morphology. Standard cephalometric measurements were compared with those provided by a Fourier description of the overall morphology. Skull patterns were divided into hyperdivergent, neutral, and hypodivergent groups (1) according to the standard thresholds of facial height ratio and (2) according to the mathematical distance between their Fourier coefficients and the Fourier coefficients of three reference plots. Linear regression analysis showed that all the Fourier variables were significantly correlated. The standard thresholds of normality used to classify patients as normal, hyperdivergent, or hypodivergent did not correlate with each other. Fourier analysis resulted in new thresholds of normality that are more accurate than previous norms developed by standard cephalometric measurements. These new thresholds take into account the overall morphologic characteristics of the patient and each separate measurement is strictly correlated with the others.