Epidemiology of Mutations in the 65-kDa Retinal Pigment Epithelium (RPE65) Gene-Mediated Inherited Retinal Dystrophies: A Systematic Literature Review.

INTRODUCTION: Inherited retinal dystrophies (IRDs) represent a genetically diverse group of progressive, visually debilitating diseases. Adult and paediatric patients with vision loss due to IRD caused by biallelic mutations in the 65-kDa retinal pigment epithelium (RPE65) gene are often clinically diagnosed as retinitis pigmentosa (RP), and Leber congenital amaurosis (LCA). This study aimed to understand the epidemiological landscape of RPE65 gene-mediated IRD through a systematic review of the literature, as the current evidence base for its epidemiology is very limited. METHODS: Medline, Embase, and other databases were searched for articles on the epidemiology of RPE65 gene-mediated IRDs from inception until June 2021. Studies were included if they were original research articles reporting the epidemiology of RP and LCA and/or proportion of RPE65 gene mutations in these clinically diagnosed or molecularly confirmed IRDs patients. RESULTS: A total of 100 studies with relevant data were included in this systematic review. The range for prevalence of LCA and RP in the literature was 1.20-2.37 and 11.09-26.43 per 100,000, respectively. The proportion of RPE65 mutations in clinically diagnosed patients with LCA was found to be between ~ 2-16% within the US and major European countries (France, Germany, Italy, Spain, and the UK). This range was also comparable to our findings in the Asian region for RPE65-LCA (1.26-16.67%). Similarly, for these European countries, RPE65-RP was estimated between 0.23 and 1.94%, and RPE65-IRD range was 1.2-14%. Further, in the Americas region, mutations in RPE65 were reported to cause 1-3% of RP and 0.8-3.7% of IRD cases. Lastly, the RPE65-IRD range was 4.81-8% in the Middle East region. CONCLUSIONS: There are significant variations in reporting of RPE65 proportions within countries as well as regions. Generating robust epidemiological evidence on RPE65 gene-mediated IRDs would be fundamental to support rare disease awareness, timely therapeutic intervention, and public health decision-making.

[Leprosy in Amazonas-impressions of the National Leprosy Program]. / Lepra in Amazonien ­ Eindrücke aus einem Kontrollprogramm.

Due to the often late detection and the neurological disability as a consequence of the disease, leprosy plays an important role in the public health system of emerging countries with the highest prevalence such as India and Brazil. The National Leprosy Control Program of the Ministry of Health and the Health Institutions of the Federal States in Brazil has implemented a strategy to ensure successful treatment of people in rural areas both at the preventive and curative level. A successful screening program, timely treatment of patients according to the stage of disease, and the introduction of preventive measures have significantly reduced the prevalence of leprosy in Brazil over the last 20 years. Due to limited medical care and socioeconomic weakness in the Amazon region in Brazil, the early eradication of leprosy does not seem to be currently realistic.

Absence of toxicity and genotoxicity in an extract of Rubus coriifolius.

Rubus coriifolius Focke is a wild plant from the Rosaceae family. It grows in both Guatemala and Mexico. The polar extract of the aerial parts of this plant has antibacterial, anti-inflammatory, and anti-protozoal activities. These properties may explain the traditional use of this plant. In vivo and in vitro assays were used to assess the genotoxic and toxic effects of an ethanol extract of the aerial parts of R. coriifolius. Three groups of rats were orally administered the R. coriifolius extract diluted in ethanol (5%) at doses of 1.89 mg/kg body weight (low dose), 4.72 mg/kg body weight (medium dose), and 9.44 mg/kg body weight (high dose) for 3 weeks. Genotoxic/cytotoxic effects induced by the R. coriifolius ethanol extract were evaluated in vivo by a micronuclei (MN) test in rat's bone marrow cells and in vitro by MN and sister chromatid exchange (SCE) in human lymphocyte cultures. In vivo genotoxicity analyses revealed that the average number of micronucleated polychromatic erythrocytes and the polychromatic erythrocyte/red blood cell ratio at all doses were not significantly different from those of the negative control. In vitro genotoxicity analyses showed that MN, SCE, and proliferative index frequencies in a human lymphocyte cell culture were not significantly different from those of the negative control. These results demonstrate that the ethanol extract of R. coriifolius aerial parts is not toxic or mutagenic (in vitro and in vivo) and does not affect cell proliferation at the concentrations analyzed.

[Tropical dermatology training in the Bundeswehr: Deployment in Manaus, Brazil]. / Tropendermatologische Ausbildung in der Bundeswehr: Einsatz in Manaus/Brasilien.

Training in tropical dermatology at the Fundação de Medicina tropical (FMT-AM) in Manaus, Brazil, offers an ideal opportunity to become familiar with the broad spectrum of tropical skin-diseases which are endemic in the tropical rainforest of the Amazon region. Besides frequently observed cases of cutaneous leishmaniasis of the new world, mucocutaneous forms of leishmaniasis and all entities of the different deep mycoses of South America are also regularly diagnosed. Of special importance in the dermatological care of the population is the early diagnosis of all clinical forms of leprosy and the long-term care of HIV patients. Modern diagnostics, including histopathology and molecular biology analytical methods, enable patients at the FMT-AM to be diagnosed without having to solely rely on clinical presentation and epidemiological data.

Effect of CLA on performance and immune response of weanling piglets.

An experiment was conducted to evaluate the effect of CLA on the immune response and performance of piglets when subjected to an immune challenge. A total of 32 weanling pigs (17 to 23 d of age) with an initial BW of 8.9 kg were allotted to a 3 × 2 factorial arrangement of treatments. There were 3 levels of dietary CLA (0%, 1%, and 2%) and 2 levels of lipopolysaccharide (LPS) challenge (unchallenged and challenged). Challenged pigs were challenged on d 7 and 21. On d 4 and 18, all pigs were inoculated with BSA for assessment of IgG production. There was no difference in growth performance among piglets receiving different CLA supplementation levels. However, LPS-challenged piglets had poorer BW (P < 0.05), ADFI (P < 0.01), and ADG (P < 0.001) compared with the control group at d 35 postweaning. Lipopolysaccharide-challenged piglets also had increased respiratory rate (P < 0.001) and rectal temperature (P < 0.001), and decreased plasma proteins, hematocrit, and white blood cell counts (P < 0.05). Production of IgG against BSA was increased in the 1% CLA supplementation group (P < 0.001), indicating that CLA has an immunomodulatory effect. Supplementation with CLA did not affect lymphocyte proliferation, percentage of CD4(+) and CD8(+) cells, plasma proteins, red and white blood cell count, respiratory rate, or rectal temperature after LPS challenge. Although CLA supplementation did not influence growth performance or certain immune system measurements, the increased IgG titers with 1% CLA dietary supplementation indicate that it has a beneficial effect on the humoral immune system of weaned piglets.

Fiber fermentability effects on energy and macronutrient digestibility, fecal traits, postprandial metabolite responses, and colon histology of overweight cats.

Considering the different potential benefits of divergent fiber ingredients, the effect of 3 fiber sources on energy and macronutrient digestibility, fermentation product formation, postprandial metabolite responses, and colon histology of overweight cats (Felis catus) fed kibble diets was compared. Twenty-four healthy adult cats were assigned in a complete randomized block design to 2 groups of 12 animals, and 3 animals from each group were fed 1 of 4 of the following kibble diets: control (CO; 11.5% dietary fiber), beet pulp (BP; 26% dietary fiber), wheat bran (WB; 24% dietary fiber), and sugarcane fiber (SF; 28% dietary fiber). Digestibility was measured by the total collection of feces. After 16 d of diet adaptation and an overnight period without food, blood glucose, cholesterol, and triglyceride postprandial responses were evaluated for 16 h after continued exposure to food. On d 20, colon biopsies of the cats were collected under general anesthesia. Fiber addition reduced food energy and nutrient digestibility. Of all the fiber sources, SF had the least dietary fiber digestibility (P < 0.05), causing the largest reduction of dietary energy digestibility (P < 0.05). The greater fermentability of BP resulted in reduced fecal DM and pH, greater fecal production [g/(cat × d); as-is], and greater fecal concentration of acetate, propionate, and lactate (P < 0.05). For most fecal variables, WB was intermediate between BP and SF, and SF was similar to the control diet except for an increased fecal DM and firmer feces production for the SF diet (P < 0.05). Postprandial evaluations indicated reduced mean glucose concentration and area under the glucose curve in cats fed the SF diet (P < 0.05). Colon mucosa thickness, crypt area, lamina propria area, goblet cell area, crypt mean size, and crypt in bifurcation did not vary among the diets. According to the fiber solubility and fermentation rates, fiber sources can induce different physiological responses in cats, reduce energy digestibility, and favor glucose metabolism (SF), or improve gut health (BP).

Phase locking of a 1.5 Terahertz quantum cascade laser and use as a local oscillator in a heterodyne HEB receiver.

We demonstrate for the first time the closure of an electronic phase lock loop for a continuous-wave quantum cascade laser (QCL) at 1.5 THz. The QCL is operated in a closed cycle cryo cooler. We achieved a frequency stability of better than 100 Hz, limited by the resolution bandwidth of the spectrum analyser. The PLL electronics make use of the intermediate frequency (IF) obtained from a hot electron bolometer (HEB) which is downconverted to a PLL IF of 125 MHz. The coarse selection of the longitudinal mode and the fine tuning is achieved via the bias voltage of the QCL. Within a QCL cavity mode, the free-running QCL shows frequency fluctuations of about 5 MHz, which the PLL circuit is able to control via the Stark-shift of the QCL gain material. Temperature dependent tuning is shown to be nonlinear, and of the order of -16 MHz/K. Additionally we have used the QCL as local oscillator (LO) to pump an HEB and perform, again for the first time at 1.5 THz, a heterodyne experiment, and obtain a receiver noise temperature of 1741 K.

Loxosceles spider bites in the state of Paraná, Brazil: 1993-2000

This study presents the epidemiological analysis of 20,699 reported spider bites involving the Loxosceles genus in the state of Paraná, Brazil, from 1993 to 2000. The incidence rate in the period was 290.24/100,000 inhabitants. The results show that 95.04 percent of the accidents occurred in two Health Regions of the state: greater metropolitan Curitiba (92.9 percent) and Irati (2.14 percent). The major incidence was recorded in greater metropolitan Curitiba (559.1/100,000). Loxosceles bites were more frequent in females (61 percent) than in males. Antivenin therapy was not necessary in 95.4 percent (19,662) of the cases. From the cases in which information about the time elapsed between the bite and medical treatment was recorded (9,679), 31.8 percent received treatment from 6 to 48 hours after the bite. Among the cases with severity rate recorded (12,096), 2.1 percent were severe, 50.4 percent moderate, and 47.4 percent mild. Seven deaths from Loxosceles bites were recorded, corresponding to a fatality rate of 0.03 percent.

Loxosceles spider bites in the state of Paraná, Brazil: 1993-2000

This study presents the epidemiological analysis of 20,699 reported spider bites involving the Loxosceles genus in the state of Paraná, Brazil, from 1993 to 2000. The incidence rate in the period was 290.24/100,000 inhabitants. The results show that 95.04% of the accidents occurred in two Health Regions of the state: greater metropolitan Curitiba (92.9%) and Irati (2.14%). The major incidence was recorded in greater metropolitan Curitiba (559.1/100,000). Loxosceles bites were more frequent in females (61%) than in males. Antivenin therapy was not necessary in 95.4% (19,662) of the cases. From the cases in which information about the time elapsed between the bite and medical treatment was recorded (9,679), 31.8% received treatment from 6 to 48 hours after the bite. Among the cases with severity rate recorded (12,096), 2.1% were severe, 50.4% moderate, and 47.4% mild. Seven deaths from Loxosceles bites were recorded, corresponding to a fatality rate of 0.03%.

Rejuvenescimento do braço: sistematização de tratamento / Arm renewing: treatment systematization

Este estudo avaliou 10 pacientes operadas com o objetivo de rejuvenescimento do braço, no período de março a novembro de 2002, no Hospital de Clínicas da Universidade Federal do Paraná. Os pacientes foram divididos em quatro grupos conforme o grau de flacidez e o volume de tecido celular subcutâneo do braço, segundo a classificação de TEIMOURIAN (1998). O tratamento cirúrgico foi individualizado para cada grupo. O primeiro grupo (duas pacientes) apresentava adiposidade moderada e flacidez mínima e foi submetido a lipoaspiração com bons resultados. O segundo grupo, (duas pacientes) apresentava moderada adiposidade e moderada flacidez de pele e optou-se pela realização de lipoaspiração do braço seguido de sutura externa formando uma prega de pele na axila. As pregas axilares evoluíram com resultado estético insatisfatório, necessitando reoperação após 6 meses com ressecção do excesso de pele, além de serem mais dolorosos que os demais grupos. O terceiro grupo (3 pacientes) apresentava flacidez moderada e adiposidade intensa, onde se indicou lipoaspiração seguido de braquioplastia com ressecção pele e fechamento em forma de “T”, obtendo-se bons resultados. O quarto grupo (duas pacientes) apresentava mínima adiposidade e intensa flacidez de pele e foram submetidas a braquioplastia tradicional com ressecção do excesso de pele evoluindo com cicatrizes extensas, porém de boa qualidade.

This study has availed 10 operated patients looking for the arm rejuvenation, in the period from march to november of 2002 in Hosp. das Clínicas da Universidade Federal do Paraná. The patients were divided in four groups according to the flaccid level and to the arm loose tissue volume, due to the TEIMOURIAN classification (1998).The surgical approach was individualized for each group. The first group(two patients) presented moderate adiposity and a few flaccid and underwent to liposuction with good results. The second group(two patients) presented mild adiposity and skin limpness, and decided a arm liposuction followed by a extern suture forming a skin ridge in the axilla. The axillary rigde developed with unsatisfactory. The third group (two patients) consists of patients who have excess fat and a fair amount of loose skin, decided a liposuction followed by a resected skin defect with the T excision with good results. The fourth group (two patients) consist of patients who skin laxity and depletion of subcutaneous fat making brachioplasty the procedure of choice, with extensive scars and visible, but tolerate.

Estudo de doppler fluxometria em retalho de abdominoplastia / Study of Eco-Doppler fluxometry in abdominoplasty flap

A abdominoplastia tem-se difundido mundialmente, tanto esteticamente como de forma reparadora, e novas técnicas estão surgindo com o objetivo de minimizar as complicações isquêmicas do retalho e melhorar o contorno corporal. No período de janeiro a julho de 2002, vinte e uma pacientes, do sexo feminino, com idade variando entre 39 e 54 anos, apresentando alteração no abdome do tipo III e IV de BOZOLA, foram submetidas a abdominoplastia associada à lipoaspiração do abdome e flancos e descolamento apenas da porção central para plicatura da diástase muscular de acordo com a técnica de Saldanha(2001). Foi realizado um estudo com doppler fluxometria colo- rida dos vasos epigástricos superiores, inferiores e suas perfurantes músculo cutâneas, no pré-operatório e no décimo quinto dia de pós-operatório, avaliando a vascularização da parede abdominal superior e inferior, contabilizando os ramos perfurantes, calibre e fluxo sangüíneo dos vasos. Este estudo comprovou, através de doppler fluxometria, a preservação dos vasos perfurantes na região periumbilical e hipocôndrio e o aumento do calibre dos vasos em 9 e do fluxo sangüíneo em 56. A manutenção da irrigação sangüínea do retalho foi demonstrada clinicamente, através da boa evolução da cicatriz e ausência de complicações, como necrose da borda do retalho e seroma.

Abdominoplasty surgery has spread universally, both as aesthetic and reconstructive procedures, and new techniques are appearing with the goal of minimizing ischemic complications of the flap and bettering body contour. From January 2002 to July 2002, twenty one female patients, range of 30 to 54 years, presenting abdominal alterations classified as type III and IV of Bozola, were submitted to abdominoplasty combined with abdominal and flank lipossuction and central portion undermining for muscular diastasis plication according to Saldanha’s technique. Eco-doppler fluxometry of the superior and inferior epigastric vessels and of their cutaneous muscular perfurans was done preoperatively and 15 days after the surgery, assessing the superior and inferior abdominal wall circulation, counting the number of perfurans vessels, the diameter and vessels flow. This study showed, through eco-doppler fluxometry, perfurans vessel preservation at the periumbelical and hypocondric areas and enhancement of vessels diameter (9) and vessels flow (56). Blood flow maintenance was demonstrated clinically through the good scar evolution and absence of complications, as flap necrosis and seroma.

The increase in spinal bone density that occurs in response to fluoride therapy for osteoporosis is not maintained after the therapy is discontinued.

In 44 osteoporotic subjects who had been treated with fluoride for 37 +/- 16 months, the fluoride was discontinued because they had shown fluoride-dependent increases in trabecular spinal bone densities from low initial levels (below the fracture threshold) to values that were equivalent to normal peak bone densities in the spines of young adults. During the subsequent period, after discontinuation of the fluoride therapy (i.e. 19 +/- 9 months), spinal bone density decreased in 73% of the subjects (i.e. 32 of 44, p < 0.03), at a rate that was comparable to the rate of the previous gain that had occurred during the treatment with fluoride (i.e. -3.23 +/- 2.39 mg/cm3 per month, compared with + 3.91 +/- 1.96 mg/cm3 per month in this, subgroup of patients, p < 0.001). Although 9 of the 44 subjects showed continuing increases in spinal bone density after discontinuation of the fluoride therapy, spinal bone density decreased in the entire group of 44 at an average rate of -1.02 +/- 4.72 mg/cm3 per month (p < 0.001, compared with the rate of the previous gain during the treatment with fluoride; i.e. +3.83 +/- 1.82 mg/cm3 per month). Surprisingly, our data showed that the rate of decrease in spinal bone density during the post-fluoride period was not affected by concurrent (undesigned) treatment with calcium, calcium plus estrogen, or calcium plus calcitriol. The cessation of fluoride therapy was also associated with a decrease in serum alkaline phosphatase activity (i.e. a decrease from the elevated levels that were observed during the period of fluoride therapy, back to the original, pre-treatment levels; p < 0.001), and that the rate of spinal bone loss after cessation of fluoride could be correlated with the prior rate of increase in serum alkaline phosphatase activity that had occurred during the treatment with fluoride (n = 44, r = 0.312, p = 0.039). Together, the observations from this retrospective analysis of data obtained from our clinical subjects suggest that fluoride-treated osteoporotic subjects who have exhibited increases in trabecular spinal bone density are at risk for bone loss after discontinuation of the fluoride therapy.

[Normative parameter characterization for the auditory brainstem response of the normal newborn]. / Caracterizacion de los parametros normativos del potencial evocado auditivo del recien nacido normal.

The auditory brainstem response generated by clicks was studied in 119 normal newborns. One ear was studied in detail at 20, 40 and 60 dBnHL, the other at 20 and 30 dBnHL, increasing the intensity if no response was found. The latency for waves I, III and V in the detailed studied ear was 2.7 +/- .39, 5.4 +/- .44 and 7.7 +/- .48, respectively. 85% of newborns had thresholds for auditory brainstem response less than 40 dBnHL, 54% less than 20 dBnHL and 15% between 40 and 60 dBnHL. These findings are compatible with conductive loss in the higher threshold group and support data from Stockard, regarding high risk groups. Additionally, our data suggests that an adequate level to screen for hearing loss in newborns is between 30 and 40 dBnHL.