Increased posterior cingulate cortex efficiency may predict cognitive impairment in asymptomatic HIV patients

Purpose: Despite antiretroviral therapy, approximately half of individuals with human immunodeficiency virus (HIV) will develop HIV-associated neurocognitive disorder (HAND). Efficiency of brain networks is of great importance for cognitive functioning, since functional networks may reorganize or compensate to preserve normal cognition. This study aims to compare efficiency of the posterior cingulate cortex (PCC) between patients with and without HAND and controls. We hypothesize HAND negative (HAND–) patients will show higher PCC efficiency than HAND positive (HAND+) patients. Methods: A total of 10 HAND + patients were compared with 9 HAND– patients and 17 gender-, age-, and education-matched controls. Resting-state functional MRI was acquired with a 3 Tesla scanner. Local efficiency, a measure of network functioning, was investigated for PCC. Network differences among HAND +, HAND– patients and controls were tested as well as correlations between network parameters and cognitive test performance in different domains. Results: HAND– patients showed significantly increased PCC efficiency compared with healthy controls (p = 0.015). No differences were observed between HAND + patients and either controls (p = 0.327) or HAND– patients (p = 0.152). In HAND– patients, PCC efficiency was positively related with cognitive performance in the attention/working memory domain (p = 0.003). Conversely, in HAND + patients, PCC efficiency was negatively correlated with performance in the abstraction/executive domain (p = 0.002). Conclusion: HAND– patients showed a higher level of PCC efficiency compared with healthy subjects, and PCC efficiency was positively related to cognitive performance. These results support the functional reorganization hypothesis, that increased PCC efficiency is a compensation technique to maintain cognitive functioning

Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-04-11T19:37:16Z No. of bitstreams: 1 Lanchote, VL. Impact of visceral....pdf: 1105142 bytes, checksum: bbbaf0c963858cd545018a3daf83495d (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-04-12T13:12:51Z (GMT) No. of bitstreams: 1 Lanchote, VL. Impact of visceral....pdf: 1105142 bytes, checksum: bbbaf0c963858cd545018a3daf83495d (MD5)Made available in DSpace on 2016-04-12T13:12:51Z (GMT). No. of bitstreams: 1 Lanchote, VL. Impact of visceral....pdf: 1105142 bytes, checksum: bbbaf0c963858cd545018a3daf83495d (MD5) Previous issue date: 2015Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Laboratório de Farmacocinética e Metabolismo. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas. Ribeirão Preto, SP, BrasilUniversidade Federal de Sergipe. Hospital Universitário. Aracaju, SE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFaculdade de Ciências Farmacêuticas de Ribeirão Preto. Laboratório de Farmacocinética e Metabolismo. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas. Ribeirão Preto, SP, BrasilFaculdade de Ciências Farmacêuticas de Ribeirão Preto. Laboratório de Farmacocinética e Metabolismo. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas. Ribeirão Preto, SP, BrasilUniversidade Federal de Sergipe. Hospital Universitário. Aracaju, SE, BrasilUniversidade Federal de Sergipe. Hospital Universitário. Aracaju, SE, BrasilInstituto Nacional de Câncer. Divisão de Farmacologia. Rio de Janeiro, RJ, BrasilAIMS: The aim of the present study was to investigate the impact of human visceral leishmaniasis (VL) and curative chemotherapy on the activity of cytochrome P450 (CYP) 3A, CYP2C9 and CYP2C19 in patients from an endemic region in Brazil. METHODS: Adult patients with parasitologically confirmed VL were given a CYP phenotyping cocktail, comprising midazolam, omeprazole and losartan, immediately before (Study phase 1), 2-3 days (phase 2) and 3-6 months (phase 3) after curative VL chemotherapy. CYP activity was assessed by the apparent clearance of midazolam (CYP3A), omeprazole/5-hydroxyomeprazol ratio in plasma (CYP2C19) and losartan/E3174 ratio in urine (CYP2C9). RESULTS: Mean values (95% confidence interval) in phases 1, 2 and 3 were, respectively: log apparent midazolam clearance, 1.21 (1.10-1.31), 1.45 (1.32-1.57) and 1.35 (1.26-1.44) ml min(-1) kg(-1) ; omeprazole/5-hydroxyomeprazole ratio, 0.78 (0.61-0.94), 0.45 (0.27-0.63) and 0.37 (0.20-0.55); losartan/E3174 ratio, 0.66 (0.39-0.92), 0.35 (0.20-0.50) and 0.35 (0.16-0.53). Analysis of variance revealed significant differences in CYP3A (P = 0.018) and CYP2C19 (P = 0.008), but not CYP2C9 (P = 0.11) phenotypic activity, across the three study phases. CONCLUSION: The phenotypic activities of CYP3A4 and CYP2C19 were significantly reduced during acute VL compared with post-chemotherapy. We propose that increased plasma concentrations of proinflammatory cytokines during active disease account for the suppression of CYP activity. The failure to detect significant changes in CYP2C9 activity in the overall cohort may reflect differential effects of the inflammatory process on the expression of CYP isoforms, although the possibility of insufficient statistical power cannot be dismissed

Relationship between High Heels and Hallux Valgus Deformity. Fact or Fiction? A 3-Dimensional Weight-bearing CT Assessment

Category: Bunion; Midfoot/Forefoot Introduction/Purpose: Evidence in the literature suggests the negative effects of using High Heels (HH), becoming a challenge for clinicians and researchers since they are welcomed by women worldwide, mainly due to the subjective power of attractiveness given to them. Although some people blame HH as one of the causes of Hallux Valgus (HV), until now, there are no studies in the literature that effectively prove a cause-effect relationship between HH and HV. The objectives of this study are: (1) to analyze whether the increase in heel height can lead to HV and (2) to evaluate whether HV can increase in severity with increasing heels. We hypothesized that an increase in heel height could cause and increase the severity of HV deformity radiographically. Methods: Comparative cross-section4-one feet from twenty-one participants (11 males and 10 females, aged 30.8 ± 8.9 years, and with Body Mass Index 25.5 ± 2.0 m kg2) were recruited. HH shoes were designed for this study with three heights for each participant: 3, 6, and 9 cm. The inclusion criteria were: no regular wearing of heels. The exclusion criteria were: Hallux Valgus diagnosis and/or any orthopedic conditions that affect the Foot and Ankle joints. Hallux Valgus Angle (HVA), Intermetatarsal Angle (IMA), First-Metatarsal Phalangeal Angle, 1st-to-5th Intermetatarsal Angle, First Tarsometatarsal Angle (axial), Second tarsometatarsal angle (axial), Hindfoot Moment Arm (HMA) (mm), Saltzman 45 angle and, Foot Ankle Offset (FAO) were measurement using semiautomated software analysis. Multiple comparisons were performed (Bonferroni's for normal distributions and Wilcoxon test for no normal distributions) when there was a main effect on an outcome (p 0.05). However, heel increases above 6 cm significantly increased HVA and IMA (p > 0.001). Based on Coughlin's classification, a 3 cm heel increase promoted a mild HV, and increases above 6 cm caused a moderate HV. Conclusion: Based on data from our study with patients without Hallux Valgus through analysis with WBCT versus High Heels, we conclude that increasing heel height can radiographically lead to Hallux Valgus deformity and progressively increase the severity. High heels above 6 cm can lead to radiographically moderate Hallux Valgus. These findings may be an essential step toward a better understanding the effects of increasing high heels on Hallux Valgus pathology. More studies are needed to support this data clinically

High-Heel Wearing Does Not Change The Forefoot Alignment In Non-Frequent Users Without Hallux Valgus: 3D Weight-Bearing Scan Study

Category: Lesser Toes; Midfoot/Forefoot Introduction/Purpose: Women wearing high heels for 20 years without Hallux valgus angle alterations make it debatable that causes Hallux valgus deformation. A recent systematic review determined that 4.13 ± 0.34 cm of heel height would improve foot weight-bearing . Wearing high heels would realign the foot, causing an inversion of the foot, which locked the navicular-cuneiform and cuneo-metatarsal joints rather than primarily rotate the metatarsophalangeal joint. Nowadays, weight-bearing scans could favor understanding the alignment mechanism involved in the foot and ankle with different shoe heights. Therefore, we aimed to determine the acute foot alignment in non-frequent HH users without Hallux valgus during stand posture. Here, we hypothesize that high heels studied by weight-bearing scans shows radiology changes linked to hindfoot alignment rather than primary forefoot rotation. Methods: This comparative cross-sectional study, participants were randomly submitted to a tridimensional weight-bearing CT. Foot alignment for barefoot and wearing custom high heels of 3, 6, and 9 cm. Forty-one feet from twenty-one participants (11 males and 10 females, aged 30.8 ± 8.9 years, and Body Mass Index 25.5 ± 2.0 m kg-2) were submitted to a tridimensional weight- bearing scan in barefoot and wearing high heels of 3, 6, and 9 cm. The inclusion criteria were: Aged between 20 and 50 years, and no regular wearing of heels.Participants were instructed to bear weight in their regular standing upright posture, dispensing the body weight uniformly between the lower limbs with the feet set at shoulder width. Declination talar, forefoot arch, foot ankle offset, 1st, 2nd, and 3rd metatarsophalangeal dorsiflexion, and metatarsal rotation and sesamoid rotation angles were compared with repeated measurement analysis and multiple comparisons as well as the raters intraclass coefficient. Results: When height increases, the declination talar angle decrease (p < 0.001), the foot ankle offset decreases (p < 0.001), the 1st, 2nd, and 3rd dorsiflexion angle increases (p < 0.001), and metatarsal rotation angle (p=0.696) and sesamoid rotation angles (p=0.649) did not change. The forefoot arch for 6 cm was higher than 3 cm (p < 0.001) and then 9 cm (p=0.001), and the forefoot arch for 9 cm was higher than 3 cm (p=0.049). Conclusion: The main finding was that increased forefoot arch, lower ankle offset, no metatarsal rotation angle, and no sesamoid rotation angle strongly suggest an acute primary hindfoot alignment adaptation mechanism rather than forefoot rotation with increase of heel heigth. The most critical mechanism combines the activation of the windlass mechanism together with a stiffer alignment of Hindfoot. Our interpretation here is supported by the lower FAO, and increased forefoot arch and metatarsophalangeal joints, giving insight into pathology foot deformation like Hallux valgus. Thus, our findings suggest that it is debatable that wearing high heels can trigger forefoot deformity

Outcomes of the Bone-Block Lapidus Arthrodesis (LapiCotton) in the Treatment of the Collapsed Foot

Category: Midfoot/Forefoot; Bunion Introduction/Purpose: Progressive collapsing foot deformity (PCFD), Hallux Valgus (HV), and Midfoot Arthritis (MA) are diseases that benefit from the Lapidus procedure due to its capability to provide a stable medial column while correcting the underlying deformity. However, the technique does not go without complications. First metatarsal shortening/dorsiflexion are not uncommon, which could be exacerbated by local anatomy/revision surgery settings. Restoring length and sagittal plane position (plantarflexion) of the first ray when treating these pathologies is paramount. Performing a primary distraction and plantarflexion fusion with an allograft wedge (LapiCotton) has been advocated in the literature, potentially allowing improved deformity correction, but with the risk of increased non-union rate. The objective of this study was to report medium-term follow-up results of the LapiCotton in patients with collapsed feet. Methods: This IRB-approved comparative prospective study assessed patients diagnosed with PCFD, HV, and MA undergoing a Lapidus bone-block fusion (LapiCotton) between August 2020 and November 2022. All patients were operated on by a single fellowship-trained foot and ankle surgeon after clinical evaluation and a weight-bearing computed tomography (WBCT). After adequate joint preparation and trials, a Lapidus pre-shaped wedge allograft was placed and fixed using available implants. Adjunctive procedures were carried out as needed. Patients were kept non-weight bearing for six weeks and followed clinically, performing a WBCT at three months and subsequent follow-up. Non-Union and complications were documented. Bone healing was determined by at least 50% of bone trabeculae crossing both graft interfaces at the WBCT. Forefoot arch angle (FFA), Meary’s angle, talonavicular coverage angle (TNCA), middle facet subluxation (MFS), and foot and ankle offset (FAO) were also obtained. Two fellowship-trained readers performed all assessments. P-values >0.05 were considered significant. Results: Fifty-eight patients (60 feet) were included, mean age 53.87 (range:18-77)/BMI 31.70 (SD:7.96). Twenty-four PCFD, 19 HV, and 17 MA had an average 15.47 months (4-31) follow-up. Cuneiform-Post implants were used in 62%, plates/screws in 25%, and Lapidus nails in 13%. Median allograft size was 9mm (mode:8mm,5-19mm). Minor complications were observed in 3% (two superficial dehiscences) and major in 7% (three deep infections [5%], and one EHL contracture [2%]). Healing at the 3-month WBCT occurred in 94.8% and only in 66% at the most-recent WBCT (mean:11.08 months; 6-20). The clinical non-union rate demanding reoperation was eight clinical non-unions 13%. Mean FFA (pre:6.89,SD:6.63; postop:14.21,SD:5.48; p< 0.001), Meary (pre:15.17,SD:8.12; postop:6.31,SD:5.61; p< 0.001), TNCA (pre:26.75,SD:11.77; postop:11.59,SD:7.91; p< 0.001), MFS (pre:36.3,SD:26; postop:23.49,SD:17.35; p< 0.001), and FAO (pre:6.71,SD:5.81; postop:2.2,SD:4.33; p< 0.001) improved after the interventions. Conclusion: Although the Lapidus bone-block arthrodesis (LapiCotton) restored many of the markers associated with foot collapse and alignment, non-union rated was noted in 13% what is on the top range of non-union rates reported in the literature for Lapidus arthrodesis. The use of allograft wedges in the fusion site probably explains our findings. The fact that the sample was heterogeneous and composed of considerably severe deformities should also be considered. Also, important to highlight that WBCT findings of fusion site healing was initially 94% at 3-months and only 66% at most recent follow-up). Additional studies and longer-term follow up are needed

Integrity of the First Metatarsal Head Vascularization and Soft-Tissue Envelope Following Minimally Invasive Chevron Osteotomy for Hallux Valgus (HV) Deformity: A Micro-CT and Anatomical Assessment

Category: Bunion; Midfoot/Forefoot Introduction/Purpose: Minimally invasive surgery (MIS) Chevron-osteotomy for HV treatment offers a surgical alternative to open surgery with minimal surgical dissection and a hypothetical decreased risk for soft-tissue complications. During this procedure, there is a concern regarding the injury to the blood supply of the 1st-metatarsal-head. The objective of this study was to assess the incidence of injuries: (1) to the soft-tissue envelope around the first metatarsal head complex and, (2) to the blood supply of the first metatarsal head and also by using Micro-CT, (3) looking for safe zones close to the first metatarsal head to perform MIS Chevron osteotomy. We hypothesized that the MIS Chevron-type osteotomy procedure would preserve the soft-tissue envelope of the first-metatarsal-head complex and the blood supply of the 1st-metatarsal-head. Methods: Sixteen HV deformity cadaveric specimens were used to perform MIS Chevron-type osteotomy of the first metatarsal head. Anatomical dissection of all specimens was then performed to assess macroscopic injury to the first metatarsal head complex soft-tissue structures, including Extensor Hallucis Longus (EHL) tendon, Extensor Hallucis Brevis (EHB) tendon, Flexor Hallucis Longus (FHL) tendon, Flexor Hallucis Brevis (FHB) tendon, Abductor Hallucis tendon, Adductor Hallucis tendon, Sesamoid complex, Dorsolateral and Dorsomedial digital branches of the first toe and the Dorsomedial digital branch to the second. Macroscopic injuries were classified using a calibrated digital caliper. Any chondral damage to the first metatarsal head was quantified in mm². To assess the amount of first metatarsal head blood supply, specimens were perfused with 200 ml of a low viscosity radiopaque polymer, MV 117 (Flowtech), preoperatively, followed by Micro-CT assessment. Descriptive statistics and percentages were utilized for categorical data. Results: We did not find injuries in the EHL, EHB, FHL, Abductor-Hallucis, and Adductor-Hallucis tendons. We found a 2mm injury in the FHB tendon in one specimen. No injuries were found in the Dorsomedial and Dorsolateral nerves of the first-toe, the Dorsomedial-nerve of the second-toe, and Medial branch of the dorsomedial-nerve of the first-toe. In 3 cases, we found an injury on first-metatarsal-head (1mm) due to the passage of the K-wire and, in 1 case, due to the inadvertent passage of the drill (4.41mm). Macroscopically and using Micro-CT, we did not observe injuries in the First-Dorsal-Metatarsal-Artery (FDMA), Lateral-Dorsal-Branch of FDMA, and Plantar-Metatarsal-Artery. Micro-CT helped estimate a safe distance to finish the proximal exit of Chevron-osteotomy (25mm from the most distal point of the first metatarsal head). Conclusion: In this study, the minimally invasive Chevron osteotomy for treating HV seems to be a technically safe procedure, presenting a low rate of iatrogenic injuries with a low degree of severity. In addition, using Micro-CT promoted a better visualization of the microvasculature that nourishes the first metatarsal head. We observed that a proximal distance of 25 mm from the most distal part of the first metatarsal head could be a safe place to finalize the Chevron osteotomy, minimizing the risk of injury to the blood supply of the first metatarsal head

Correlação entre espessura cortical frontal e desempenho de funções executivas em pacientes com infecção pelo vírus da imunodeficiência humana

OBJETIVO: Investigar a relação entre a espessura cortical medida pela ressonância magnética em regiões frontais e o desempenho em instrumentos que avaliam funções executivas em pacientes com HIV positivo. MATERIAIS E MÉTODOS: Participaram deste estudo 22 pacientes HIV-positivos, com déficits em funções executivas, sob terapia antirretroviral, idades entre 45 e 65 anos e escolaridade entre 3 e 20 anos. Foi realizada ressonância magnética com sequências convencionais, T1 3D, processado pelo Freesurfer para verificar espessura cortical. Instrumentos de avaliação das funções executivas: Teste de Trilhas, Wisconsin, Hayling, Dígitos (WAIS-III), fluência verbal ortográfica e Stroop. Para análise da relação espessura versus cognição, utilizou-se coeficiente de correlação de Pearson. RESULTADOS: Correlações significativas foram encontradas entre escores de: Wisconsin e espessura das regiões pré-central e orbitofrontal lateral à direita e pré-central esquerda; Teste de Trilhas e espessura da área pré-central direita e cíngulo anterior caudal esquerdo; e Teste Hayling e espessura da área lateral orbitofrontal esquerda. CONCLUSÃO: As correlações existentes entre medidas de espessura cortical pela ressonância magnética e desempenho cognitivo sugerem que os déficits executivos em pacientes HIV-positivos relacionam-se a uma redução da espessura cortical das regiões frontais