Comprehensive germline mutation analysis and clinical profile in a large cohort of Brazilian xeroderma pigmentosum patients.

BACKGROUND: Xeroderma pigmentosum (XP) patients present a high risk of developing skin cancer and other complications at an early age. This disease is characterized by mutations in the genes related to the DNA repair system. OBJECTIVES: To describe the clinical and molecular findings in a cohort of 32 Brazilian individuals who received a clinical diagnosis of XP. METHODS: Twenty-seven families were screened for germline variants in eight XP-related genes. RESULTS: All patients (N = 32) were diagnosed with bi-allelic germline pathogenic or potentially pathogenic variants, including nine variants previously undescribed. The c.2251-1G>C XPC pathogenic variant, reported as the founder mutation in Comorian and Pakistani patients, was observed in 15 cases in homozygous or compound heterozygous. Seven homozygous patients for POLH/XPV variants developed their symptoms by an average age of 7.7 years. ERCC2/XPD, DDB2/XPE and ERCC5/XPG variants were found in a few patients. Aside from melanoma and non-melanoma skin tumours, a set of patients developed skin sebaceous carcinoma, leiomyosarcoma, angiosarcoma, mucoepidermoid carcinoma, gastric adenocarcinoma and serous ovarian carcinoma. CONCLUSIONS: We reported a high frequency of XPC variants in 32 XP Brazilian patients. Nine new variants in XP-related genes, unexpected non-skin cancer lesions and an anticipation of the clinical manifestation in POLH/XPV cases were also described.

Absorption, scattering, and radiation force efficiencies in the longitudinal wave scattering by a small viscoelastic particle in an isotropic solid.

Analytical expressions of the absorption, scattering, and elastic radiation force efficiency factors are derived for the longitudinal plane wave scattering by a small viscoelastic particle in a lossless solid matrix. The particle is assumed to be much smaller than the incident wavelength, i.e., the so-called long-wavelength (Rayleigh) approximation. The efficiencies are dimensionless quantities that represent the absorbed and scattering powers and the elastic radiation force on the particle. In the quadrupole approximation, they are expressed in terms of contrast functions (bulk and shear moduli, and density) between the particle and solid matrix. The results for a high-density polyethylene particle embedded in an aluminum matrix agree with those obtained with the partial wave expansion method. Additionally, the connection between the elastic radiation force and forward scattering function is established through the optical theorem. The present results should be useful for ultrasound characterization of particulate composites, and the development of implanted devices activated by radiation force.

Scattering of a longitudinal Bessel beam by a sphere embedded in an isotropic elastic solid.

The scattering of a longitudinal Bessel beam of arbitrary order by a sphere embedded in an isotropic solid matrix is theoretically analyzed. The spherical inclusion can be made of a viscoelastic, elastic, or fluid-filled isotropic material. In the analysis, the absorbing, scattering, and extinction efficiency factors are obtained, e.g., the corresponding power per characteristic beam intensity per sphere's cross-section area. Furthermore, the extended optical theorem, which expresses the extinction efficiency in terms of an integral of the longitudinal scattering function is derived. Several features of zeroth- and first-order Bessel beams scattering in solids are illustrated considering a polymer adhesive (cured) sphere embedded in a stainless steel matrix. For instance, omnidirectional scattering can be achieved by choosing specific values of the half-cone angle of the Bessel beam, which is the beam's geometrical parameter. Additionally, it is demonstrated that mode suppression leads to lower absorption inside the inclusion when compared to plane wave scattering results.

Periodontal infections and community-acquired pneumonia: a case-control study.

The aim of this study was to evaluate if the presence of periodontal infections (PI) is associated with community-acquired pneumonia (CAP) in a group of patients admitted to a hospital. A total of 140 patients were enrolled in this case-control study, with 70 patients having CAP (case group) and the other 70 patients diagnosed with other systemic diseases (control group). A periodontal examination was carried out to assess pocket probing depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), and presence of bacterial plaque (BP). CAL and BOP showed higher scores in the case group over the control group. They were, respectively, 3.16 ± 2.43 mm and 0.33 ± 0.24 % for the case group, and 1.99 ± 2.23 mm and 0.25 ± 0.24 % for the control group (p < 0.05). High scores for BP were observed in both groups (case: 97.1 %; control: 98.6 %, p = 1.0000). Chronic periodontitis (CP) was more frequent in patients with CAP (case: 61.4 %; control: 41.4 %). The presence of moderate or severe CP increased the risk for CAP [odds ratio (OR) = 4.4, 95 % confidence interval (CI) = 1.4-13.8], even when adjusted for age, ethnicity, gender, and smoking. Moderate and severe chronic periodontitis were associated with CAP in this study.

The Hubble constant troubled by dark matter in non-standard cosmologies.

The Standard Cosmological Model has experienced tremendous success at reproducing observational data by assuming a universe dominated by a cosmological constant and dark matter in a flat geometry. However, several studies, based on local measurements, indicate that the universe is expanding too fast, in disagreement with the Cosmic Microwave Background. Taking into account combined data from CMB, Baryon Acoustic Oscillation, and type Ia Supernovae, we show that if the mechanism behind the production of dark matter particles has at least a small non-thermal origin, one can induce larger values of the Hubble rate [Formula: see text], within the [Formula: see text]CDM, to alleviate the trouble with [Formula: see text]. In the presence of non-standard cosmology, however, we can fully reconcile CMB and local measurements and reach [Formula: see text]-74 [Formula: see text].

TNF-alpha and IL-8: serum levels and gene polymorphisms (-308G>A and -251A>T) are associated with classical biomarkers and medical history in children with sickle cell anemia.

Sickle cell anemia (SCA) is a disorder characterized by a heterogeneous clinical outcome. In the present study, we investigated the associations between Tumor Necrosis Factor-alpha (TNF-alpha) -308G>A and Interleukin 8 (IL-8) -251A>T gene polymorphisms, medical history and classical biomarkers in children with steady-state SCA. In total, 210 SCA patients aged 2-21 years and 200 healthy controls were studied. Gene polymorphisms, betaS-globin haplotypes and a 3.7-kb deletion in alpha2-thalassemia (α2-thal3.7 kb) were investigated by PCR/RFLP analysis, and cytokine levels were determined by ELISA. Splenomegaly (p=.032) was more prevalent among children younger than 5 years of age. The A allele of the TNF-alpha -308G>A gene polymorphism and the presence of α2-thal3.7 kb were associated with an increase risk of splenic sequestration events (p=.001; p=.046), while the T allele of the IL-8 -251A>T gene polymorphism was considered to be a protective factor for splenomegaly events (p=.032). Moreover, the A allele of the TNF-alpha -308G>A gene polymorphism was associated with high TNF-alpha levels (p=.021), and the hemoglobin F and hemoglobin S haplotypes were correlated with serum levels of IL-8. The logistic regression analysis showed significant effects of the TNF-alpha and IL-8 gene polymorphisms, beta(S)-globin gene haplotypes and α2-thal3.7 kb on the occurrence of splenic sequestration events. Our study emphasizes that the identification of new genetic and immunological biomarkers and their associations with classical markers is an important strategy to elucidate the underlying causes of different SCA phenotypes and their effects on patient outcome.

Three-dimensional finite element analysis of stress distribution in peri-implant bone with relined dentures and different heights of healing caps.

The purpose of this study was to evaluate the influence of height of healing caps and the use of soft liner materials on the stress distribution in peri-implant bone during masticatory function in conventional complete dentures during the healing period by using finite element analysis. Three-dimensional models of a severely resorbed mandible with two recently placed implants in the anterior region were created and divided into the following situations: (i) submerged implants, (ii) healing cap at gingival level and (iii) 1·5-mm supragingival. All these situations were also analysed for a conventional complete denture and a denture relined with a 3-mm-thick layer of soft liner material. The models were exported to mechanical simulation software that presented two simulations, one with load in the inferior right canine (35 N) and the other in the inferior right first molar (50 N). Data were evaluated using Maximum Principal Stress provided by the software. All models showed a stress concentration in the cortical bone corresponding to the cervical part of the implant. The simulations with non-submerged implants showed higher values of stress concentration than those that were submerged. Likewise, soft liner materials presented better results than when the denture base was not relined. The height of the healing caps seems to have a direct influence on the stress distribution in the peri-implant bone during the healing period. Considering the values obtained in this study, the use of soft liners with submerged implants seems to be the most suitable method to use during the period of osseointegration.

In silico evaluation of the stress fields on the cortical bone surrounding dental implants: Comparing root-analogue and screwed implants.

Tooth loss is a problem that affects both old and young people. It may be caused by several conditions, such as poor oral hygiene, lifestyle choices or even diseases like periodontal disease, tooth grinding or diabetes. Nowadays, replacing a missing tooth by an implant is a very common process. However, many limitations regarding the actual strategies can be enumerated. Conventional screwed implants tend to induce high levels of stress in the peri-implant bone area, leading to bone loss, bacterial bio-film formation, and subsequent implant failure. In this sense, root-analogue dental implants are becoming promising solutions for immediate implantation due to their minimally invasive nature, improved bone stress distribution and because they do not require bone drilling, sinus lift, bone augmentation nor other traumatic procedures. The aim of this study was to analyse and compare, by means of FEA, the stress fields of peri-implant bone around root-analogue and screwed conventional zirconia implants. For that purpose, one root-analogue implant, one root-analogue implant with flaps, two conventional implants (with different threads) and a replica of a natural tooth were modelled. COMSOL was used to perform the analysis and implants were subjected to two simultaneous loads: 100 N axially and 100 N oblique (45°). RESULTS: revealed that root-analogue implants, namely with flaps, should be considered as promising alternatives for dental implant solutions since they promote a better stress distribution in the cortical bone when compared with conventional implants.

Acoustic radiation force and torque exerted on a small viscoelastic particle in an ideal fluid.

We provide a detailed analysis on the acoustic radiation force and torque exerted on a homogeneous viscoelastic particle in the long-wave limit (i.e. the particle radius is much smaller than the incident wavelength) by an arbitrary wave. We assume that the particle behaves as a linear viscoelastic solid, which obeys the fractional Kelvin-Voigt model. Simple analytical expressions for the radiation force and torque are obtained. The developed theory is used to describe the interaction of acoustic waves (traveling and standing plane waves, and zero- and first-order Bessel beams) in the MHz-range with polymeric particles, namely lexan, low-density (LDPE) and high-density (HDPE) polyethylene. We found that particle absorption is chiefly the cause of the radiation force due to a traveling plane wave and zero-order Bessel beam when the frequency is smaller than 5MHz (HDPE), 3.9MHz (LDPE), and 0.9MHz (lexan). Whereas in a standing wave field, the radiation force is mildly changed due to dispersion inside the particle. We also show that the radiation torque caused by a first-order Bessel beam varies nearly quadratic with frequency. These findings may enable new possibilities of particle handling in acoustophoretic techniques.

Correlação de parâmetros biométricos e produtivos em colônias de Melipona scutelaris / Correlation of biometric and productive parameters in colonies of Melipona scutelaris

The objective of this research was to estimate the correlations between the biometric and reproductive parameters of Melipona scutelaris. Four collections were performed with 30-day intervals, consisting of the evaluation of each colony, considering the following parameters: honey pot size and volume (HPS and VHP), estimated honey production (EHP), number of combs (NC), mean diameter of the combs (MDC), height of the combs (HC), height of rearing cells (HRC), number of pups (NP) population (POP) and wax envelope in pups. The data were analyzed using the SAS software (2004), and the Pearson correlation coefficient was used for the correlation calculations. The correlations of the studied variables of production and biometrics of Melipona scutellaris colonies made it possible to perceive that the variable number of honey pots (NHP) present a higher correlation with HPS, EPH, DMC, HRC, NP and POP, followed by size of pots of honey (HPS) with: VHP, EHP, MDC, HC and POP. For future studies using the productive and biometric characteristics of the bees Melipona scutellaris can be considered for EPH, VHP, EPH, NC and POP, as variable responses.(AU)

Abnormal facilitation of the response to transcranial magnetic stimulation in patients with Parkinson's disease.

We studied the facilitation of the motor evoked potential (MEP) elicited with transcranial magnetic stimulation by increasing the stimulus intensity and the degree of voluntary activation of the target muscle in patients with Parkinson's disease (PD) and in normal volunteers. The threshold intensity for eliciting MEPs with the muscle at rest did not differ in PD patients and normal subjects. At rest, stimuli of similar intensity, related to the individual's threshold, elicited MEPs with amplitudes consistently larger in patients than in normal subjects, although when we compared the averaged MEP amplitude across all stimulus intensities, the differences reached only borderline statistical significance. Voluntary muscle activation elicited a smaller increase in the MEP area in PD patients than in normal subjects. Increasing the degree of voluntary muscle activation at fixed stimulus intensities elicited a smaller increase of MEP amplitude, duration, and area in PD patients than in normal subjects. These results suggest that control of the excitability of the motor system is abnormal in PD patients, with enhancement of excitability at rest and weak energization during voluntary muscle activation.

Akinesia in Parkinson's disease. I. Shortening of simple reaction time with focal, single-pulse transcranial magnetic stimulation.

We studied the effects of transcranial magnetic stimulation (TMS) of the motor cortex on simple reaction time (RT) in 10 patients with Parkinson's disease compared with 10 age-matched normal controls. The subjects flexed their right elbow rapidly in response to a visual go-signal. In random trials, TMS was applied to the left motor cortex at varying delays after the go-signal. In trials without TMS, RT was longer in the patients. However, in the trials with subthreshold TMS, RT in the patients became as fast as RT in trials without TMS in the controls. This shortening was associated with normalization of the voluntary triphasic EMG pattern and the pre-movement cortical excitability increase.

Akinesia in Parkinson's disease. II. Effects of subthreshold repetitive transcranial motor cortex stimulation.

We studied the effects of repetitive transcranial stimulation of the motor cortex (rTMS) on choice reaction time (cRT), movement time (MT), and error rate (ER) in a serial reaction-time task in six medicated patients with Parkinson's disease (PD) and 10 age-matched normal controls. In normal subjects, subthreshold 5-Hz rTMS did not significantly change cRT, slightly shortened MT, but increased ER. In the patients, rTMS significantly shortened cRT and MT without affecting ER. These effects did not impair procedural learning. Performance on a grooved peg-board test was improved by rTMS in the same PD patients, especially when they were off medications, but worsened in the normal subjects. Repetitive, subthreshold motor cortex stimulation can improve performance in patients with PD and could be useful therapeutically.

Rapid reversible modulation of human motor outputs after transient deafferentation of the forearm: a study with transcranial magnetic stimulation.

Reorganization of corticospinal pathways after spinal cord injury and amputations leads to increased excitability of motor pathways targeting muscles proximal to the level of interruption of efferents from the CNS. To study the timing of these changes, we have recorded motor evoked potentials (MEPs) in the arm muscles of three normal subjects before, during, and after anesthetic block of the forearm and hand. The amplitudes of MEPs from biceps, which was the muscle immediately proximal to the block, gradually increased with anesthesia and then returned to preanesthesia levels within approximately 20 minutes after anesthesia was ended. MEPs from the contralateral arm were unaffected. Such rapid changes strongly suggest unmasking of preexisting synaptic connections, due to disinhibition at cortical or subcortical levels, as the mechanism underlying acute modulation of motor outputs.

No evidence of hearing loss in humans due to transcranial magnetic stimulation.

Prompted by the description of hearing loss in rabbits exposed to the acoustic artifact of magnetic stimulation, we compared the results of audiologic studies before and after exposure to transcranial magnetic stimulation in humans. We found no evidence of temporary or permanent threshold shifts in any of the subjects, even in those exposed to transcranial magnetic stimulation repeatedly for several years. Risk of hearing loss from the acoustic artifact of magnetic stimulation, as evaluated by audiograms, tympanograms, acoustic reflexes, and auditory evoked potentials, seems to be small in humans.

Effects of abrupt and gradual withdrawal from long-term haloperidol treatment on open field behavior of rats.

The effects of abrupt and gradual withdrawal from long-term haloperidol treatment on rat open field behavior was studied. Abrupt withdrawal induced a significant increase in all parameters of activity observed except defecation, this increase being higher 72 h after the last haloperidol injection. Results were considered to be a consequence of supersensitivity of central dopaminergic receptors. These differences were almost unobservable in animals gradually withdrawn, thus suggesting that the phenomenon is reversible.

Optimal focal transcranial magnetic activation of the human motor cortex: effects of coil orientation, shape of the induced current pulse, and stimulus intensity.

We studied the effects of coil orientation, stimulus intensity, and shape of the induced current pulse on the amplitudes of motor evoked potentials in the left abductor pollicis brevis of 10 normal adults who had transcranial magnetic stimulation. The optimal direction of currents induced in the brain is approximately perpendicular to the central sulcus, flowing diagonally from back to front. The most effective coil orientation depends on the shape of the induced current pulse and, when the first and second phases of the pulse are of similar size, also on the intensity of stimulation. Optimal mapping of the human motor cortex with magnetic stimulation requires knowledge of the influences of all these factors.

Electrophysiologic studies in leprosy.

The author reviews the literature on electromyography and nerve conduction velocity studies in leprosy. It is concluded that these studies can be helpful in the early diagnosis of neural involvement, in the elucidation of pathophysiological mechanisms, and in the follow-up of patients under medical and/or surgical treatment.