Repetitive transcranial magnetic stimulation of human MT+ reduces apparent motion perception

We investigated the effects of repetitive transcranial magnetic stimulation (rTMS) over the human cerebral cortex on apparent motion perception. Previous studies have shown that human extrastriate visual area MT+ (V5) processes not only real but also apparent motion. However, the functional relevance of MT+ on long-range apparent motion perception remains unclear. Here, we show direct evidence for the involvement of MT+ in apparent motion perception using rTMS, which is known to temporarily inhibit a localized region in the cerebral cortex. The results showed that apparent motion perception decreased after applying rTMS over MT+, but not after applying rTMS over the control region (inferior temporal gyrus). The decrease in performance caused by applying rTMS to MT+ suggests that MT+ is a causally responsible region for apparent motion perception, and thus, further supports the idea that MT+ plays a major role in the perception of motion.     

Melatonin alterations and brain acetylcholine lesions in sleep disorders in Cockayne syndrome

Background: Cockayne syndrome (CS) is a genetic disorder caused by deficient nucleotide excision repair. Patients with CS exhibit progeroid features, developmental delay, and various neurological disorders; they are also known to suffer from sleep problems, which have never been investigated in detail. Objective: The aim of this study is to investigate the pathogenesis of sleep disorders in patients with CS. Methods: We performed a questionnaire survey of the families of patients with CS, enzyme-linked immunosorbent analyses of the melatonin metabolite, 6-sulphatoxymelatonin (6-SM), in the patients’ urine, and immunohistochemistry in the hypothalamus, the basal nucleus of Meynert (NbM), and the pedunculopontine tegmental nucleus (PPN) in four autopsy cases. Results: Sleep–wakefulness rhythms were disturbed in patients with CS, and these disturbances seemed to be related to a reduced urinary excretion of 6-SM. In addition, although the hypothalamic nuclei were comparatively preserved, acetylcholine neurons (AchNs) were severely decreased in the NbM and PPN. Conclusions: AchNs modulate both arousal and rapid eye movement sleep, and selective lesions of AchNs in the PPN and/or NbM in combination with disturbed melatonin metabolism might be involved in the sleep disorders in CS.     

Effects of Heat Stress on Ocular Blood Flow During Exhaustive Exercise

The hypothesis that heat stress reduces the ocular blood flow response to exhaustive exercise was tested by measuring ocular blood flow, blood pressure, and end- tidal carbon dioxide partial pressure (P_ETCO₂) in 12 healthy males while they performed cycle ergometer exercise at 75% of the maximal heart rate at ambient temperatures of 20°C (control condition) and 35°C (heat condition), until exhaustion. The blood flows in the retinal and choroidal vasculature (RCV), the superior temporal retinal arteriole (STRA) and the superior nasal retinal arteriole (SNRA) were recorded at rest and at 6 and 16 min after the start of exercise period and at exhaustion [after 16 ± 2 min (mean ± SE) and 24 ± 3 min of exercise in the heat and control condition, respectively]. The mean arterial pressure at exhaustion was significantly lower in the heat condition than in the control condition at both 16 min and exhaustion. The degree of P_ETCO₂ reduction did not differ significantly between the two thermal conditions at either 16 min or exhaustion. The blood flow velocity in the RCV significantly increased from the resting baseline value at 6 min in both thermal conditions (32 ± 6% and 25 ± 5% at 20°C and 35°C, respectively). However, at 16 min the increase in RCV blood flow velocity had returned to the resting baseline level only in the heat condition. At exhaustion, the blood flows in the STRA and SNRA had decreased significantly from the resting baseline value in the heat condition (STRA: -19 ± 5% and SNRA: -30 ± 6%), and SNRA blood flow was lower than that in the control condition (-14 ± 6% vs -30 ± 6% at 20°C and 35°C, respectively), despite the finding that both thermal conditions induced the same reductions in P_ETCO₂ and vascular conductance. These findings suggested that the heat condition decreases or suppresses ocular blood flow via attenuation of pressor response during exhaustive exercise.

Key Points

• The ocular (retinal and choroidal) blood flow response to exhaustive exercise with heat stress is unknown.
• We hypothesized that the heat stress decreases ocular blood flow response to exhaustive exercise, since cerebral flow, which is regulated similarly to ocular flow, was reported to decrease during heat stress.
• To test this hypothesis, ocular blood flow was measured during exhaustive exercise at 20°C (control condition) and 35°C (heat condition).
• At exhaustion in the heat condition, the ocular flow response was suppressed or decreased with an attenuated pressor response.
• It is suggested that the heat condition decreases or suppresses the ocular blood flow to exhaustive exercise via attenuation of pressor response.

Key Words: Hyperthermia, exercise, healthy subjects, retinal circulation, choroidal circulation, laser-speckle flowgraphy     

Kinematics of the thoracic spine in trunk lateral bending: in vivo three-dimensional analysis

Background contextIn vivo three-dimensional kinematics of the thoracic spine in trunk lateral bending with an intact rib cage and soft tissues has not been well documented. There is no quantitative data in the literature for lateral bending in consecutive thoracic spinal segments, and there has not been consensus on the patterns of coupled motion with lateral bending.PurposeTo demonstrate segmental ranges of motion (ROMs) in lateral bending and coupled motions of the thoracic spine.Study designIn vivo three-dimensional biomechanics study of the thoracic spine.Patient sampleFifteen healthy male volunteers.Outcome measuresComputed analysis by using voxel-based registration.MethodsParticipants underwent computed tomography of the thoracic spine in three supine positions: neutral, right maximum lateral bending, and left maximum lateral bending. The relative motions of vertebrae were calculated by automatically superimposing an image of vertebrae in a neutral position over images in bending positions, using voxel-based registration. Mean values of lateral bending were compared among the upper (T1–T2 to T3–T4), the middle-upper (T4–T5 to T6–T7), the middle-lower (T7–T8 to T9–T10), and the lower (T10–T11 to T12–L1) parts of the spine.ResultsAt lateral bending, the mean ROM (±standard deviation) of T1 with respect to L1 was 15.6°±6.3° for lateral bending and 6.2°±4.8° for coupled axial rotation in the same direction as lateral bending. The mean lateral bending of each spinal segment with respect to the inferior adjacent vertebra was 1.4°±1.3° at T1–T2, 1.3°±1.2° at T2–T3, 1.4°±1.3° at T3–T4, 0.9°±0.9° at T4–T5, 0.8°±1.0° at T5–T6, 1.1°±1.1° at T6–T7, 1.7°±1.2° at T7–T8, 1.3°±1.2° at T8–T9, 1.6°±0.7° at T9–T10, 1.8°±0.8° at T10–T11, 2.3°±1.0° at T11–T12, and 2.2°±0.8° at T12–L1. The smallest and the largest amounts of lateral bending were observed in the middle-upper and the lower parts, respectively. There was no significant difference in lateral bending between the upper and the middle-lower parts. Coupled axial rotation of each segment was generally observed in the same direction as lateral bending. However, high variability was found at the T2–T3 to T5–T6 segments. Coupled flexion was observed at the upper and middle parts, and coupled extension was observed at the lower part.ConclusionsThis study revealed in vivo three-dimensional motions of consecutive thoracic spinal segments in trunk lateral bending. The thoracolumbar segments significantly contributed to lateral bending. Coupled axial rotation generally occurred in the same direction with lateral bending. However, more variability was observed in the direction of coupled axial rotation at T2–T3 to T5–T6 segments in the supine position. These results are useful for understanding normal kinematics of the thoracic spine.     

Percutaneous autologous concentrated bone marrow grafting in the treatment for nonunion

The purpose of this study was to evaluate the clinical and radiographic treatment effects of percutaneous autologous concentrated bone marrow grafting in nonunion cases and to evaluate the effectiveness of this grafting procedure. We enrolled 17 cases those had atrophic changes due to continuous nonunion for over 9 months after injury and had undergone low-intensity pulsed ultrasound treatment for more than 3 months. The site of nonunion was the femur in 10 cases, the tibia in 5 cases, the humerus in 1 case, and the ulna in 1 case. They underwent percutaneous autologous concentrated bone marrow grafting and continued low-intensity pulsed ultrasound stimulation treatment after grafting. Patients were evaluated using the visual analogue scale for pain at immediately before the procedure, 3, 6, and 12 months after grafting. Plain radiographs of the affected site were taken and evaluated about the healing of the nonunion site at each clinical evaluation. As quantitative assessment, CT scans were undertaken before the procedure and 6 months after grafting. The visual analogue scale pain score was reduced consistently after grafting in all patients. About the healing at the nonunion site, 11 and 13 cases of bone union were observed at 6 and 12 months after grafting. The mean volume of callus formation based on CT images was 4,147 (262–27,392) mm³ total between grafting and 6 months. Percutaneous autologous concentrated bone marrow grafting is an effective procedure for the treatment of patients with nonunion.     

Citalopram and escitalopram plasma drug and metabolite concentrations: genome-wide associations

Aims

Citalopram (CT) and escitalopram (S-CT) are among the most widely prescribed selective serotonin reuptake inhibitors used to treat major depressive disorder (MDD). We applied a genome-wide association study to identify genetic factors that contribute to variation in plasma concentrations of CT or S-CT and their metabolites in MDD patients treated with CT or S-CT.

Methods

Our genome-wide association study was performed using samples from 435 MDD patients. Linear mixed models were used to account for within-subject correlations of longitudinal measures of plasma drug/metabolite concentrations (4 and 8 weeks after the initiation of drug therapy), and single-nucleotide polymorphisms (SNPs) were modelled as additive allelic effects.

Results

Genome-wide significant associations were observed for S-CT concentration with SNPs in or near the CYP2C19 gene on chromosome 10 (rs1074145, P = 4.1 × 10⁻⁹) and with S-didesmethylcitalopram concentration for SNPs near the CYP2D6 locus on chromosome 22 (rs1065852, P = 2.0 × 10⁻¹⁶), supporting the important role of these cytochrome P450 (CYP) enzymes in biotransformation of citalopram. After adjustment for the effect of CYP2C19 functional alleles, the analyses also identified novel loci that will require future replication and functional validation.

Conclusions

In vitro and in vivo studies have suggested that the biotransformation of CT to monodesmethylcitalopram and didesmethylcitalopram is mediated by CYP isozymes. The results of our genome-wide association study performed in MDD patients treated with CT or S-CT have confirmed those observations but also identified novel genomic loci that might play a role in variation in plasma levels of CT or its metabolites during the treatment of MDD patients with these selective serotonin reuptake inhibitors.     

Retrolaminar versus epidural block for postoperative analgesia after minor video-assisted thoracic surgery: a retrospective,matched, non-inferiority study

BackgroundThe role of thoracic epidural analgesia (TEA) for postoperative analgesia after video-assisted thoracic surgery (VATS) is still controversial. Some studies have reported the efficacy of ultrasound-guided retrolaminar block (RLB) for the postoperative management of pain after chest wall surgery. The purpose of this study was to compare the postoperative analgesic efficacy and adverse effects of ultrasound-guided RLB with those of TEA in patients undergoing minor VATS procedures.MethodsA total of 192 relevant records of patients were enrolled in this study. We reviewed electronic medical records of patients undergoing minor VATS procedures under general anesthesia. The primary outcome was the median differences in the numerical rating scale (NRS) scores during rest between the groups at the morning of postoperative day 1 (POD 1m). A propensity-matched analysis incorporating preoperative variables was used to compare the efficacy of postoperative analgesia in two groups.ResultsOverall, 94 patients were identified for analysis. Propensity score matching resulted in 47 patients in each group. There were no significant differences in the NRS scores between the two groups. The median differences in NRS scores during rest between the two groups at POD 1m were under 1, which indicates non-inferiority of RLB. There were no significant differences in the incidence of adverse effects and rescue dose of analgesic consumption between the two groups.ConclusionsThe analgesic effects of continuous ultrasound-guided RLB were non inferior to those of TEA for minor VATS procedures.     

Cryptococcal meningitis following umbilical cord blood transplantation,association between the occurrence of cryptococcal infection and tacrolimus discontinuation among allogeneic hematopoietic stem cell recipients

Few cases of cryptococcal infection following umbilical cord blood transplantation (UCBT) have been reported. We report a case, where cryptococcal infection occurred soon after rapidly reducing the dose of tacrolimus in a UCBT recipient who received micafungin prophylaxis during the early phase of transplantation. The etiology of cryptococcal infection following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including UCBT, might be associated with rapid dose-reduction of calcineurin inhibitors, such as tacrolimus during early phase of allo-HSCT. To our knowledge, this is the first English-language report to describe in detail a case of cryptococcal meningitis with fungemia during early phase of UCBT.     

Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence

Despite their high degree of genomic similarity, reminiscent of their relatively recent separation from each other ( approximately 6 million years ago), the molecular basis of traits unique to humans vs. their closest relative, the chimpanzee, is largely unknown. This report describes a large-scale single-contig comparison between human and chimpanzee genomes via the sequence analysis of almost one-half of the immunologically critical MHC. This 1,750,601-bp stretch of DNA, which encompasses the entire class I along with the telomeric part of the MHC class III regions, corresponds to an orthologous 1,870,955 bp of the human HLA region. Sequence analysis confirms the existence of a high degree of sequence similarity between the two species. However, and importantly, this 98.6% sequence identity drops to only 86.7% taking into account the multiple insertions/deletions (indels) dispersed throughout the region. This is functionally exemplified by a large deletion of 95 kb between the virtual locations of human MICA and MICB genes, which results in a single hybrid chimpanzee MIC gene, in a segment of the MHC genetically linked to species-specific handling of several viral infections (HIV/SIV, hepatitis B and C) as well as susceptibility to various autoimmune diseases. Finally, if generalized, these data suggest that evolution may have used the mechanistically more drastic indels instead of the more subtle single-nucleotide substitutions for shaping the recently emerged primate species.     

Early detection of doxorubicin-induced myocardial damage by ultrasound tissue characterization with integrated backscatter.

Doxorubicin (DXR) is one of the most effective antineoplastic agents, but its use is limited by its myocardial toxicity. Myocardial injury reduces the cyclic variation of integrated backscatter (CV-IBS) and so the present study was designed to investigate whether CV-IBS can be used to detect the early phase of myocardial damage in patients receiving DXR. Thirty-four subjects constituted the study population, none of whom showed clinically evident heart failure. CV-IBS was obtained for both the interventricular septum and the left ventricular posterior wall in the parasternal short-axis view. Standard echographic measures of left ventricular function were also made. Subjects without DXR exposure or evident cardiac diseases served as controls. The total dose of DXR administered per patient was 339+/-164 mg/m2 (range: 95-680 mg/m2). Conventional echographic parameters, including left ventricular wall thickness, dimensions, fractional shortening, and ejection fraction, showed no significant differences between the 2 groups. In contrast, CV-IBS was significantly decreased in the DXR group compared with the control group (septum: 4.7+/-1.7 vs 7.2+/-1.9 dB, p<0.0001; posterior wall: 6.7 +/-2.2 vs 8.0+/-1.6 dB, p<0.05). CV-IBS can be used as an early indicator of DXR-induced myocardial damage in patients demonstrating normal left ventricular systolic function.