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Abstract In non-anuric patients undergoing peritoneal dialysis (PD), residual kidney function (RKF) is a main contributor to fluid and solute removal and an independent predictor of survival. We investigated if urine volume could be used to estimate renal clearances and removal of urea, creatinine, and phosphorus in PD patients. The observational, cross-sectional study included 93 non-anuric prevalent PD patients undergoing continuous ambulatory PD (CAPD; n = 34) or automated PD (APD; n = 59). Concentrations of urea, creatinine and phosphorus in serum and in 24-h collections of urine volume were measured to calculate weekly residual renal clearance (L/week) and removed solute mass (g/week). Median [interquartile range], 24-h urine output was 560 [330–950] mL and measured GFR (the mean of creatinine and urea clearances) was 3.24 [1.47–5.67] mL/min. For urea, creatinine and phosphorus, residual renal clearance was 20.60 [11.49–35.79], 43.02 [19.13–75.48] and 17.50 [8.34–33.58] L/week, respectively, with no significant differences between CAPD and APD. Urine volume correlated positively with removed solute masses (rho = 0.82, 0.67 and 0.74) and with weekly residual renal clearances (rho = 0.77, 0.62 and 0.72 for urea, creatinine, and phosphorus, respectively, all p

By September 2022, the uptake of at least one dose of COVID-19 vaccine in the Dutch adult population was 84%. Ecological studies have indicated a lower uptake in certain population groups. We aimed to investigate determinants of COVID-19 vaccine uptake in the Netherlands at individual level to evaluate and optimize implementation of the vaccination program and generate hypotheses for research on drivers of, and barriers to, vaccination. A retrospective database study was performed including the entire Dutch population ≥ 18. Vaccination data (5 January 2021–18 November 2021) were at individual levels linked to sociodemographic data. Random forest analyses ranked sociodemographic determinants of COVID-19 vaccine uptake. The most important determinant was age; uptake increased until the age of 80 (67% in 18–35 years, 92% in 67–79 years, and 88% in those > 80). Personal income and socioeconomic position ranked second and third, followed by migration status. Uptake was lower among individuals in the lowest income group (69%), those receiving social benefits (56%), and individuals with two parents born abroad (59%). Our finding that age is the most important determinant for uptake likely reflects the prioritisation of elderly in the programme and the general understanding of their increased vulnerability. However, our findings also reveal important other disparities in vaccine uptake. How to best address this inequity in future vaccination campaigns requires further research.

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Aim: To evaluate the aesthetic self-perception capacity of adolescents from public schools regarding the presence of oral alterations from malocclusions. Methods: Cross-sectional and quantitative study with 374 adolescents between 16 and 18 years old, belonging to public schools in the city of Parnaíba, Piauí. The adolescents were separated by gender (male and female) and examined for malocclusions. The problem identified for each participant was recorded for later comparison of the influence of its presence with aesthetic self-perception. Then, all adolescents, including those who demonstrated normal occlusion during the clinical evaluation, answered a questionnaire containing eight questions about their perception of their own smile and its impact on their interpersonal relationships. Self-perception was also analyzed by comparing the responses of those with normal occlusion with that of malocclusion individuals. Student's t-tests were used to verify if there was a difference between the groups. Results: The most prevalent malocclusions after clinical examination were midline deviations, crowding and diastemas, and the ones that most scored in the adolescents' perception were crowding, misalignment and diastemas. Conclusion: The adolescents were able to perceive the aesthetic alterations resulting from malocclusions, being determinants of dissatisfaction when smiling. They were not ashamed to smile, did not consider that the ideal smile would improve their self-esteem and that misaligned teeth would not interfere with flirting and interpersonal relationships.

O câncer é definido como um tumor maligno, caracterizado pelo crescimento descontrolado de células anormais, dando origem a tumores conhecida como metástase. Objetivo: Atuação do farmacêutico na equipe multidisciplinar no tratamento oncológico. Métodos: Foi realizado um estudo qualitativo e descritivo com 3 farmacêuticos Hospitalares, com o foco de interesse o trabalho desenvolvido pelo farmacêutico junto à equipe multidisciplinar no tratamento oncológico. Resultados: Foram relatadas dificuldades de atuação com relação ao setor de pediatria, pois envolve processo mais detalhado de atenção farmacêutica e aceitação do corpo clinico. As medidas adotadas pelos profissionais no tratamento oncológico é feita através de atualizações e da farmácia clinica. E de acordo com registros de cada paciente que informa o melhor procedimento de tratamento e estão dispostos em registrado de prontuário. Conclusão: O farmacêutico, com caráter humanístico, é capaz de tornar mais leve a vida de quem sofre de uma doença tão dura como o câncer.

BACKGROUND:Miltefosine (MF) is the only oral drug available for treatment of visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). Although the drug is effective and well tolerated in treatment of VL, the efficacy and safety of MF for longer treatment durations (>28 days) in PKDL remains unclear. This study provides an overview of the current knowledge about safety and efficacy of long treatment courses with MF in PKDL, as a strategy in the VL elimination in South Asia. METHODOLOGY/PRINCIPAL FINDINGS:Literature was searched systematically for articles investigating MF treatment in PKDL. A meta-analysis included eight studies (total 324 PKDL patients) to estimate the efficacy of MF in longer treatment regimens (range 6-16 weeks). We found a per-protocol (PP) initial cure rate of 95.2% (95%CI 89.6-100.8) and a PP definite cure rate of 90% (95%CI 81.6-96.3). Descriptive analysis showed that 20% of patients experienced adverse events, which mostly had an onset in the first week of treatment and were likely to get more severe after four weeks of treatment. Gastrointestinal (GI) side effects such as vomiting, nausea, diarrhoea, and abdominal pain were most common. CONCLUSIONS/SIGNIFICANCE:Longer treatment regimens with MF are effective in PKDL patients in India, however with the caveat that the efficacy has recently been observed to decline. GI side effects are frequent, although mostly mild or moderate. However, on the basis of limited data, we cannot conclude that longer MF treatment regimens are safe. Moreover, VL and PKDL pharmacovigilance studies indicate a risk for serious adverse events, questioning the safety of MF. The provision of safer treatment regimens for PKDL patients are therefore recommended. Until these regimens are identified, it should be considered to halt the use of MF monotherapy for PKDL in order to preserve the drug's efficacy.

Considerando a implantação da UHE Belo Monte e consequente enchimento do Reservatório Xingu, foi executado monitoramento da dinâmica e qualidade das águas subterrâneas no âmbito do Programa de Monitoramento das Águas Subterrâneas. Os estudos realizados na área do bairro Jardim Independente I, localizado na cidade de Altamira - PA partiram da demanda de se avaliar a existência ou não de um aquífero suspenso e de se verificar a relação de causa-efeito entre a formação do reservatório Xingu (UHE Belo Monte) e consequente elevação dos níveis freáticos com a elevação e flutuação do nível da água da “lagoa” localizada no bairro em referência. O regime de chuvas é o principal parâmetro para explicar as variações dos níveis freáticos dos poços de monitoramento em toda a área urbana de Altamira. Após longos períodos com chuvas acumuladas, superiores à média histórica, há uma tendência dos níveis freáticos se elevarem de forma consistente, padrão observado em toda a área urbana de Altamira antes, durante e após o enchimento do Reservatório. A chuva também é o principal parâmetro para explicar a variação da elevação da lâmina d'água da lagoa existente na região do bairro Jardim Independente I; onde o nível se eleva a partir das chuvas que caem diretamente sobre a lâmina d'água e pelo escoamento superficial da água, no entorno da lagoa e em sua direção. os dados ainda permitem concluir que não há conexão hdráulica entre o Reservatório Xingu e o aquífero local situado sob a lagoa, que por sua vez está vinculada à exposição do nível freático de um aquífero suspenso com localização restrita. Em síntese, os dados e análises mostram que há um aquífero suspenso, materializado por i) diferença de carga hidráulica deste com o aquífero local; ii) padrões de qualidade das águas distintos entre os mesmos, iii) existência deum aquitarde constituído por camda de argila interposto entre ambos, com espessura entre 3,5 e 8m, portanto sem conexão direta do aquífero suspenso com o Reservatório.

Background. Cardiovascular diseases are leading causes of death worldwide. Recent studies suggest that infection by some viruses, including the human papillomavirus (HPV), may increase the risk of developing atheromatous lesions on coronary arteries. However, there is a lack of data regarding the possible association between HPV infection and coronary artery disease (CAD) in women. Objective. To investigate whether HPV infection is associated with the occurrence of CAD among climacteric women. Methods. The presence of CAD and cervical HPV DNA was investigated in 52 climacteric women. Social and demographic variables and metabolic profiles were also investigated. Results. Among 27 women with CAD, 16 were positive for HPV, whereas 11 were negative. The presence of cervical HPV was strongly associated with CAD, after adjusting for demographic variables, health and sexual behaviors, comorbidities, and known cardiovascular risk factors. HPV-positive women showed a greater likelihood of having CAD (odds ratio [OR] = 3.74; 95% confidence interval [CI]: 1.16 to 11.96) as compared with HPV-negative women, particularly those infected with high-risk HPV types (OR = 4.90; 95% CI: 1.26 to 19.08). Conclusion. These results support the hypothesis that HPV infection might be associated with CAD among climacteric women, though further studies are needed to investigate the mechanisms involved.

RESUMO Objetivo Verificar a sensibilidade, especificidade e estabelecer pontos de corte para o índice Porcentagem de Consoantes Corretas Revisado (PCC-R) em crianças com e sem transtorno fonológico falantes do Português Brasileiro. Método Participaram 72 crianças com idade entre 5:00 e 7:11 anos, sendo 36 sem queixas de alteração de fala e linguagem e 36 crianças com diagnóstico fonoaudiológico de transtorno fonológico. O índice de gravidade PCC-R foi aplicado nas provas de nomeação de figuras e de imitação de palavras do Teste de Linguagem Infantil ABFW. Os resultados foram analisados estatisticamente. Foi realizada a curva Roc e obtidos os valores de sensibilidade e especificidade do índice. Resultados O grupo de crianças sem transtorno fonológico apresentou valores do PCC-R maiores nas duas provas, independentemente do gênero dos participantes. O valor de corte na prova de nomeação de figuras foi de 93,4%, com sensibilidade de 0,89 e especificidade de 0,94, independentemente da idade. Já na prova de imitação de palavras, os valores obtidos variaram de acordo com a idade. Para a faixa etária ≤6:5 anos, o valor de corte foi de 91,0%, com sensibilidade de 0,77 e especificidade de 0,94. Para a faixa etária >6:5 anos, o valor de corte foi de 93,9%, com sensibilidade de 0,93 e especificidade de 0,94. Conclusão Dada a alta sensibilidade e especificidade do PCC-R, o índice foi efetivo na discriminação e identificação de crianças com e sem transtorno fonológico.

Extraction of maxillary third molar always comes as a challenge for any dental practitioner owing to its limited accessibility and minimal space for instrument placement. Moreover, the complications related to faulty extraction technique can never be ignored. We have here described a simple and easy method of extraction of the maxillary third molar tooth using hockey stick elevators which can solve most of the problems that are faced by dental surgeons in the extraction of maxillary third molars. This technique has proved its efficacy and has been time tested for removal of a maxillary third molar providing a good alternative for routine extraction techniques of maxillary third molars.

OBJETIVO: Avaliar a percepção das mães de crianças entre zero e três anos sobre a associação da estimulação ambiental e o desenvolvimento normal das crianças atendidas em uma unidade de saúde em São Luís, Maranhão, e identificar o nível de entendimento das mães quanto à estimulação do ambiente familiar em que a criança está inserida. MÉTODOS: Realizou-se pesquisa qualitativa exploratória. Os sujeitos estudados foram 15 mães de crianças de zero a três anos atendidas na Unidade de Saúde Antônio Carlos Reis, Cidade Olímpica, em São Luís, Maranhão, de outubro de 2009 a março de 2010. Os instrumentos da coleta de dados foram prontuários médicos, entrevistas semiestruturadas aplicadas em domicílio com pais, observação participante e visita domiciliar. RESULTADOS: A maioria das mães pesquisadas era adolescente, solteira, do lar, com ensino fundamental incompleto e renda familiar de 0 a 0,5 salário mínimo. As principais dificuldades encontradas foram: despreparo em educar os filhos, baixo nível de resolutividade das situações cotidianas e ausência paterna na convivência familiar. Analisou-se o modo como as mães associam as carências ambientais e o desenvolvimento infantil normal. CONCLUSÕES: As mães apresentaram percepção relativa ao ambiente em que seus filhos vivem e que a falta de estimulação nestes ambientes interfere no desenvolvimento de tais crianças. Observou-se, assim, a necessidade de melhora dos níveis de estimulação e dos vínculos entre criança, família e profissionais de saúde.

Clinical and experimental studies have demonstrated some negative effect of hypertension on bone mineral density. The aim of this study was to evaluate bone healing and trabecular bone area (TBA) in spontaneously hypertensive rats (SHR), a well-established model of essential hypertension, when compared to normotensive rats (NTR). A critical-size defect was surgically created in the right tibia of SHR (n = 12) and normotensive rats (NTR; n = 12), while the contralateral tibia was left intact. Eight days later, the animals were sacrificed and the specimens processed in order to obtain decalcified sections. The area of newly-formed bone (NB) within the defect of the right tibia and the TBA in the left tibia were histometrically evaluated. At 8 days post-operative, SHR presented a significantly smaller area of NB when compared to NTR (p < 0.05). In addition, SHR demonstrated a lower TBA than NTR group. In conclusion, the present study demonstrated that SHR rats presented a disturbed bone healing and reduced TBA.

Zinc finger motifs are distributed amongst many eukaryotic protein families, directing nucleic acid-protein and protein-protein interactions. Zinc finger protein 106 (ZFP106) has previously been associated with roles in immune response, muscle differentiation, testes development and DNA damage, although little is known about its specific function. To further investigate the function of ZFP106, we performed an in-depth characterization of Zfp106 deficient mice (Zfp106(-/-)), and we report a novel role for ZFP106 in motor and sensory neuronal maintenance and survival. Zfp106(-/-) mice develop severe motor abnormalities, major deficits in muscle strength and histopathological changes in muscle. Intriguingly, despite being highly expressed throughout the central nervous system, Zfp106(-/-) mice undergo selective motor and sensory neuronal and axonal degeneration specific to the spinal cord and peripheral nervous system. Neurodegeneration does not occur during development of Zfp106(-/-) mice, suggesting that ZFP106 is likely required for the maintenance of mature peripheral motor and sensory neurons. Analysis of embryonic Zfp106(-/-) motor neurons revealed deficits in mitochondrial function, with an inhibition of Complex I within the mitochondrial electron transport chain. Our results highlight a vital role for ZFP106 in sensory and motor neuron maintenance and reveal a novel player in mitochondrial dysfunction and neurodegeneration., (© The Author 2015. Published by Oxford University Press.)

Transgenic mouse models expressing mutant superoxide dismutase 1 (SOD1) have been critical in furthering our understanding of amyotrophic lateral sclerosis (ALS). However, such models generally overexpress the mutant protein, which may give rise to phenotypes not directly relevant to the disorder. Here, we have analysed a novel mouse model that has a point mutation in the endogenous mouse Sod1 gene; this mutation is identical to a pathological change in human familial ALS (fALS) which results in a D83G change in SOD1 protein. Homozgous Sod1(D83G/D83G) mice develop progressive degeneration of lower (LMN) and upper motor neurons, likely due to the same unknown toxic gain of function as occurs in human fALS cases, but intriguingly LMN cell death appears to stop in early adulthood and the mice do not become paralyzed. The D83 residue coordinates zinc binding, and the D83G mutation results in loss of dismutase activity and SOD1 protein instability. As a result, Sod1(D83G/D83G) mice also phenocopy the distal axonopathy and hepatocellular carcinoma found in Sod1 null mice (Sod1(-/-)). These unique mice allow us to further our understanding of ALS by separating the central motor neuron body degeneration and the peripheral effects from a fALS mutation expressed at endogenous levels., (© The Author 2014. Published by Oxford University Press.)

Mutations in the skeletal muscle channel (SCN4A), encoding the Nav1.4 voltage-gated sodium channel, are causative of a variety of muscle channelopathies, including non-dystrophic myotonias and periodic paralysis. The effects of many of these mutations on channel function have been characterized both in vitro and in vivo. However, little is known about the consequences of SCN4A mutations downstream from their impact on the electrophysiology of the Nav1.4 channel. Here we report the discovery of a novel SCN4A mutation (c.1762A>G; p.I588V) in a patient with myotonia and periodic paralysis, located within the S1 segment of the second domain of the Nav1.4 channel. Using N-ethyl-N-nitrosourea mutagenesis, we generated and characterized a mouse model (named draggen), carrying the equivalent point mutation (c.1744A>G; p.I582V) to that found in the patient with periodic paralysis and myotonia. Draggen mice have myotonia and suffer from intermittent hind-limb immobility attacks. In-depth characterization of draggen mice uncovered novel systemic metabolic abnormalities in Scn4a mouse models and provided novel insights into disease mechanisms. We discovered metabolic alterations leading to lean mice, as well as abnormal AMP-activated protein kinase activation, which were associated with the immobility attacks and may provide a novel potential therapeutic target., (© The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterised by the degeneration of upper and lower motor neurons. Recent advances in our understanding of some of the genetic causes of ALS, such as mutations in SOD1, TARDBP, FUS and VCP have led to the generation of rodent models of the disease, as a strategy to help our understanding of the pathophysiology of ALS and to assist in the development of therapeutic strategies. This review provides detailed descriptions of TDP-43, FUS and VCP models of ALS, and summarises potential therapeutics which have been recently trialled in rodent models of the disease. This article is part of a Special Issue entitled: Animal Models of Disease., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The calpains are physiologically important Ca(2+)-activated regulatory proteases, which are divided into typical or atypical sub-families based on constituent domains. Both sub-families are present in mammals, but our understanding of calpain function is based primarily on typical sub-family members. Here, we take advantage of the model organism Caenorhabditis elegans, which expresses only atypical calpains, to extend our knowledge of the phylogenetic evolution and function of calpains. We provide evidence that a typical human calpain protein with a penta EF hand, detected using custom profile hidden Markov models, is conserved in ancient metazoans and a divergent clade. These analyses also provide evidence for the lineage-specific loss of typical calpain genes in C. elegans and Ciona, and they reveal that many calpain-like genes lack an intact catalytic triad. Given the association between the dysregulation of typical calpains and human degenerative pathologies, we explored the phenotypes, expression profiles, and consequences of inappropriate reduction or activation of C. elegans atypical calpains. These studies show that the atypical calpain gene, clp-1, contributes to muscle degeneration and reveal that clp-1 activity is sensitive to genetic manipulation of [Ca(2+)](i). We show that CLP-1 localizes to sarcomeric sub-structures, but is excluded from dense bodies (Z-disks). We find that the muscle degeneration observed in a C. elegans model of dystrophin-based muscular dystrophy can be suppressed by clp-1 inactivation and that nemadipine-A inhibition of the EGL-19 calcium channel reveals that Ca(2+) dysfunction underlies the C. elegans MyoD model of myopathy. Taken together, our analyses highlight the roles of calcium dysregulation and CLP-1 in muscle myopathies and suggest that the atypical calpains could retain conserved roles in myofilament turnover., Competing Interests: The authors have declared that no competing interests exist.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with no cure. Breakthroughs in understanding ALS pathogenesis came with the discovery of dominant mutations in the superoxide dismutase 1 gene (SOD1) and other genes, including the gene encoding transactivating response element DNA binding protein-43 (TDP-43). This has led to the creation of animal models to further our understanding of the disease and identify a number of ALS-causing mechanisms, including mitochondrial dysfunction, protein misfolding and aggregation, oxidative damage, neuronal excitotoxicity, non-cell autonomous effects and neuroinflammation, axonal transport defects, neurotrophin depletion, effects from extracellular mutant SOD1, and aberrant RNA processing. Here we summarise the SOD1 and TDP-43 animal models created to date, report on recent findings supporting the potential mechanisms of ALS pathogenesis, and correlate this understanding with current developments in the clinic.

The phenomenon that is known as RNA mediated interference (RNAi) was first observed in the nematode C. elegans. The application of RNAi has now been widely disseminated and the mechanisms underlying the pathway have been uncovered using both genetics and biochemistry. In the worm, it has been demonstrated that RNAi is easily adapted to high throughput analysis and screening protocols. Hence, given the availability of whole genome sequences, RNAi has been used extensively as a tool for annotating gene function. Genetic screens performed with C. elegans have also led to the identification of genes that are essential for RNAi or that modulate the RNAi process. The identification of such genes has made it possible to manipulate and enhance the RNAi response. Moreover, many of the genes identified in C. elegans have been conserved in other organisms. Thus, opportunities are available for researchers to take advantage of the insights gained from the worm and apply them to their own systems in order to improve the efficiency and potency of the RNAi response.

Unlabelled: Complex regional pain syndrome is often treated with the sympatholytic guanethidine and a local anesthetic in a Bier's block. The efficacy of this treatment has been questioned. Because local anesthetics inhibit the norepinephrine uptake transporter, we hypothesized that this variable efficacy results from the local inhibiting the uptake of guanethidine. In this study, we tested this hypothesis by using a sympathetically innervated mouse vas deferens preparation. Organ bath-mounted mouse vasa deferentia were electrically stimulated in the absence and presence of guanethidine, prilocaine, procaine, and cocaine in various combinations. Prilocaine (1 mM) induced an immediate inhibition of twitch response (maximum 100% after 2 min) that fully reversed after washing. Guanethidine (3 microM) also inhibited twitching by 95% +/- 3% in 15 min, but this effect was only partially reversed after 1 h of washing (33% +/- 12% of control). When prilocaine and guanethidine were added in combination, a reversal of 80% +/- 13% (at 1 h) was observed. Procaine (300 micro M) produced a transient increase (152% +/- 14%) in response. When co-incubated with guanethidine (3 microM), the twitch was reduced to 24% +/- 4% of control and was reversed to 77% +/- 7% after 1 h. Cocaine (30 microM) inhibited the twitch response to 53% +/- 8%, which was fully reversed by 1 h of washing. When co-incubated with guanethidine, the response was reduced to 39% +/- 6% of control and was reversed to 86% +/- 10% after 1 h. In all cases, the reversal produced by the combination was significantly more intense (P < 0.05) than that produced by guanethidine alone. Local anesthetics reduce the sympatholytic actions of guanethidine, and this may explain the variable efficacy of guanethidine in the treatment of complex regional pain syndrome., Implications: In this study, with a sympathetically innervated vas deferens preparation, local anesthetics reduced the efficacy of the sympatholytic guanethidine, questioning its co-administration in the pain clinic.

Use of intravenous guanethidine for the treatment of complex regional pain syndrome type I is of variable efficacy. Guanethidine injection is painful, so local anaesthetic is co-administered. We hypothesize that local anaesthetic inhibits uptake of guanethidine and hence reduces its efficacy. In this study we have examined the effects of a range of local anaesthetic agents on the uptake of [3H]norepinephrine ([3H]NE) (as a surrogate for guanethidine) and the binding of [3H]nisoxetine to the NE transporter in cultured SH-SY5Y human neuroblastoma cells. All local anaesthetic agents inhibited NE uptake with a rank order cocaine>tetracaine>procaine(esters), dibucaine > bupivacaine > prilocaine > lidocaine (amides). In addition all anaesthetic agents displaced [3H]nisoxetine with a rank order cocaine > tetracaine > dibucaine > procaine > prilocaine > bupivacaine > lidocaine. There was a positive correlation between [3H]NE uptake and [3H]nisoxetine binding. Our data suggest that when local anaesthetic and guanethidine are co-administered the former may reduce uptake of the latter and hence reduce the clinical efficacy of guanethidine.