Prognostic value of phrenic nerve conduction study in amyotrophic lateral sclerosis: Systematic review and meta-analysis.

OBJECTIVES: To assess the prognostic value of phrenic nerve conduction (PNC) in amyotrophic lateral sclerosis (ALS). METHODS: We conducted a systematic review to identify studies reporting on PNC, and mortality and/or forced vital capacity (FVC) in patients with ALS. We searched Medline, EMBASE, and Web of Science. Two independent authors selected studies and extracted data. Risk of bias was assessed using the QUIPS tool. Hazard-ratios and correlation coefficients were pooled using a random effects generic inverse-variance model. Evidence quality was evaluated with GRADE. RESULTS: In the pooled analysis, patients with CMAP-amplitude equal or below 0.4 mV are 2.021 more likely to die over the studied period (95%CI 1.161-3.522; I2 = 55.9%; 338 participants). CMAP-amplitude showed a moderate positive correlation with FVC (r = 0.400, 95%CI = 0.226-0.550; I2 = 69.77%; 381 participants). However, there was a weak negative correlation between CMAP-latency and FVC (r = -0.235; 95%CI = -0.447 to -0.024; I2 = 15.92%; 112 participants). CONCLUSIONS: There is moderate-quality evidence that CMAP-amplitude of the PNC is correlated with FVC. Results favour a predictive value for mortality, but the risk of bias is high. SIGNIFICANCE: PNC is a simple test that should be considered to assess respiratory function in ALS, especially in patients with bulbar involvement or cognitive impairment.

Intradermal Delivery of a Near-Infrared Photosensitizer Using Dissolving Microneedle Arrays.

Nodular basal cell carcinoma is a deep skin lesion and one of the most common cancers. Conventional photodynamic therapy is limited to treatment of superficial skin lesions. The parenteral administration of near-IR preformed photosensitizers suffers from poor selectivity and may result in prolonged skin photosensitivity. Microneedles (MNs) can provide localized drug delivery to skin lesions. Intradermal delivery of the preformed near-IR photosensitizer; 5,10,15,20-tetrakis(2,6-difluoro-3-N-methylsulfamoylphenyl bacteriochlorin (Redaporfin™) using dissolving MN was successful in vitro and in vivo. MN demonstrated complete dissolution 30 min after skin application and showed sufficient mechanical strength to penetrate the skin to a depth of 450 µm. In vitro deposition studies illustrated that the drug was delivered and detected down to 5 mm in skin. In vivo biodistribution studies in athymic nude mice Crl:NU(NCr)-Foxn1nu showed both fast initial release and localized drug delivery. The MN-treated mice showed a progressive decrease in the fluorescence intensity at the application site over the 7-day experiment period, with the highest and lowest fluorescence intensities measured being 9.2 × 1010 ± 2.5 × 1010 and 3.8 × 109 ± 1.6 × 109 p/s, respectively. By day 7, there was some migration of fluorescence away from the site of initial MN application. However, the majority of the body surfaces showed fluorescence levels that were comparable to those seen in the negative control group. This work suggests utility for polymeric MN arrays in minimally invasive intradermal delivery to enhance photodynamic therapy of deep skin lesions.

Dynamic hyperinflation during activities of daily living in COPD patients.

The objective of this study was to investigate whether some activities of daily living (ADLs) usually related to dyspnea sensation in patients with chronic obstructive pulmonary disease (COPD) are associated with dynamic lung hyperinflation (DH) and whether the use of simple energy conservation techniques (ECTs) might reduce this possible hyperinflation. Eighteen patients (mean age: 65.8 ± 9.8 years) with moderate-to-severe COPD performed six ADLs (walking on a treadmill, storing pots, walking 56 meters carrying a 5-kilogram weight, climbing stairs, simulating taking a shower, and putting on shoes) and had their inspiratory capacity (IC) measured before and after each task. The patients were moderately obstructed with forced expiratory volume in 1 second (FEV1): 1.4 ± 0.4 L (50% ± 12.4); FEV1/forced vital capacity: 0.4 ± 8.1; residual volume/total lung capacity: 52.7 ± 10.2, and a reduction in IC was seen after all six activities (p < 0.05): (1) going upstairs, 170 mL; (2) walking 56 meters carrying 5 kilogram weight, 150 mL; (3) walking on a treadmill without and with ECT, respectively, 230 mL and 235 mL; (4) storing pots without and with ECT, respectively, 170 mL and 128 mL; (5) taking a shower without and with ECT, respectively, 172 mL and 118 mL; and (6) putting on shoes without and with ECT, respectively, 210 mL and 78 mL). Patients with moderate to severe COPD develop DH after performing common ADLs involving the upper and lower limbs. Simple ECTs may avoid DH in some of these ADLs.

Synthesis and characterization of biomimetic nanogels for immunorecognition.

Biomimetic nanoparticles are promising materials for biomedical and biotechnological applications. Cationic poly(N-isopropylacrylamide) (PNIPAM) nanogels containing charged amine groups brought by addition of 2-aminoethylmethacrylate hydrochloride (AEMH) or N-(3-aminopropyl) methacrylamide hydrochloride (APMH) as co-monomers were prepared by surfactant-free precipitation polymerization. The influence of the relative amount and mode of addition of the co-monomer on both the size and the amine group density of the nanogel particles was studied. Two nanogels, one prepared using APMH (1%mol/mol NIPAM, in batch) and another with AEMH (2%mol/mol NIPAM, by shot addition) as co-monomers, were selected for the covalent coupling of a Protein L-mimic ligand to free amine groups on the particles. The ability of the synthesized biomimetic nanoparticles for recognizing and binding human IgG (hIgG) molecules was assessed and the selectivity toward immunoglobulin molecules evaluated.

Associações entre diferentes fatores de risco para doenças cardiovasculares e hipertensão arterial de pacientes com dislipidemia pertencentes a uma comunidade universitária / Associations between differents risk factors to arterial cardiovascular diseases and arterial hypertension of patients with dyslipidemics pertaining to a university community

Este trabalho teve por objetivo discutir a relação entre a hipertensão arterial sistêmica e alguns fatores de risco para doença arterial coronariana, em indivíduos com dislipidemia, pertencentes a uma comunidade universitária. Foram obtidos dados clínicos e laboratoriais de 140 pacientes durante o período de março de 1997 a dezembro de 2004. A população analisada constitui-se de 76 mulheres e 64 homens, com idade entre 27 a 81 anos. Calculou-se o percentual de ocorrência dos fatores de risco e estes foram associados à hipertensão. A prevalência avaliada foi de 11,25% para o diabetes mellitus, 25,8% de tabagismo e 39,28% de hipertensão,sendo que para estes últimos 12,57% tinham hipertensão leve, 19,65% estágio moderado e 7,06% estágio grave. Conclui-se que a hipertensãoé o fator de risco mais prevalente na população em estudo, sendo importante uma abordagem interdisciplinar e multiprofissional, a fim de maximizar o controle da hipertensão e as medidas de prevenção para doenças cardiovasculares.

Affinity-based methodologies and ligands for antibody purification: advances and perspectives.

Many successful, recent therapies for life-threatening diseases such as cancer and rheumatoid arthritis are based on the recognition between native or genetically engineered antibodies and cell-surface receptors. Although naturally produced by the immune system, the need for antibodies with unique specificities and designed for single application, has encouraged the search for novel antibody purification strategies. The availability of these products to the end-consumer is strictly related to manufacture costs, particularly those attributed to downstream processing. Over the last decades, academia and industry have developed different types of interactions and separation techniques for antibody purification, affinity-based strategies being the most common and efficient methodologies. The affinity ligands utilized range from biological to synthetic designed molecules with enhanced resistance and stability. Despite the successes achieved, the purification "paradigm" still moves interests and efforts in the continuous demand for improved separation performances. This review will focus on recent advances and perspectives in antibody purification by affinity interactions using different techniques, with particular emphasis on affinity chromatography.

Adsorption of human IgG on to poly(N-isopropylacrylamide)-based polymer particles.

Thermosensitive poly(N-isopropylacrylamide)-based polymer particles were synthesised, and screened for the adsorption of human immunoglobulin G (hIgG). At pH 9 the adsorption on microgel particles was strongly affected by temperature, approximately 40 mg hIgG/g support (90% of initial hIgG) being adsorbed at 40 degrees C but only 10% of initial hIgG at 25 degrees C. At pH 5 the maximum adsorbed amount (20 mg hIgG/g support) was similar for both temperatures. The adsorption of hIgG on to charged poly(methyl methacrylate)/poly(N-isopropylacrylamide) core-shell latexes was negligible (5-10 mg hIgG/g support) at the same temperature and pH conditions. The lower adsorption of hIgG onto the core-shell particles is explained by steric interactions due to the small size of the shell.

Inteligência computacional avaliando o risco coronariano / Computational intelligence evaluating coronary arterial risk

Apesar de estarmos numa época de tecnologia e de avanços em estudos e diagnósticos em relação à doença arterial coronária (DAC), a realidade é que tal patologia ainda representa a princiapal causa de mortalidade e morbidade no mundo ocidental. Neste trabalho foi explorada a potencialidade das redes neurais e Lógica Fuzzy no estado de fatores de risco de doenças arteriais coronarianas. Na sua forma mais geral, uma rede neural, é uma máquina que é projetada para modelar a maneira como o cérebro realiza uma tarefa particular ou função de interesse, por meio da sua propriedade de aprender a partir de um conjunto de dados de entrada. Participaram deste estudo 33 indivíduos funcionários da Universidade Federal de Santa Catarina (UFSC) no mês de maio de 2001. A partir de dados clínicos e laboratoriais obtidos desses pacientes (idade, sexo, colesterol total, HDL colesterol, LDL colesterol, triglicerideos, tabagismo, Hipertensão Arterial Sistêmica,Diabetes Melittus, massa corporal, estatura, perímetro da cintura e do abdomen) se calculou o índice de massa corporal, indice cintura quadril, relação colesterol HDL colestetol e também o risco para a doença arterial coronariana. Neste estudo, aplicando a Teoria de Fuzzy Sets (Conjuntos Difusos ou Nebulosos) aos princípios da lógica clássica e resultados de rede neural sobre este conjunto de dados, foi possível determinar um valor percentual pertinente ao grau de risco de doença coronária de cada indivíduo. Concluiu-se que o sistema proposto mostrou maior potencialidade em relação à forma tradicional de avaliação para.