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Abstract This study aimed to (1) set a reference value for anterior center edge angle (ACEA) for preoperative planning of periacetabular osteotomy (PAO), (2) investigate the effects of pelvic rotation and inclination from false profile (FP) radiographs on the measured ACEA, and (3) determine the “appropriate range of positioning” for FP radiograph. This single-centered, retrospective study analyzed 61 patients (61 hips) who underwent PAO from April 2018 and May 2021. ACEA was measured in each digitally reconstructed radiography (DRR) image of the FP radiograph reconstructed in different degrees of pelvic rotation. Detailed simulations were performed to determine the “appropriate range of positioning” (0.67

We present a rare phenomenon of a soft tumor hanging on the woman’s left upper arm that underwent necrosis from the distal aspect during chemotherapy for pancreatic cancer. The benign tumor, pedunculated lipofibroma, originally had normal color for 10 years and then became necrotic when she was treated with gemcitabine and nab-paclitaxel. Necrosis stopped in conjunction with chemotherapy cessation. Dermatologists must remember that nab-paclitaxel could develop necrosis of a skin tumor.

Blind football players use head movements to accurately identify sound location when trapping a ball. Accurate sound localization is likely important for motor learning of ball trapping in blind football. However, whether head movements affect the acquisition of ball-trapping skills remains unclear. Therefore, this study examined the effect of head movements on skill acquisition during ball trapping. Overall, 20 sighted male college students were recruited and assigned to one of the following two groups: the conventional training group, where they were instructed to move leftward and rightward to align their body with the ball's trajectory, and the head-movement-focused group, where they were instructed to follow the ball with their faces until the ball touched their feet, in addition to the conventional training instructions. Both groups underwent a 2-day training for ball trapping according to the specific instructions. The head-movement-focused group showed a decrease in errors in ball trapping at near distances and with larger downward head rotations in the sagittal plane compared to the conventional training group, indicating that during the skill acquisition training for ball trapping, the sound source can be localized more accurately using larger head rotations toward the ball. These results may help beginner-level players acquire better precision in their movements while playing blind football. [ABSTRACT FROM AUTHOR]

The Japanese domestic tobacco cultivar Kokubu (syn. Kou-fan) is highly resistant to powdery mildew, and this trait is controlled by recessive alleles at two loci. To show the molecular mechanism of powdery mildew resistance of Kokubu, the transcripts and genomic sequences of tobacco Mildew resistance locus O ( MLO) orthologues were compared between powdery mildew-resistant and -susceptible cultivars. Two MLO orthologues ( Nt MLO1 and Nt MLO2) corresponding to powdery mildew susceptibility were expressed in tobacco leaves. However, the transcripts of both Nt MLO genes in the powdery mildew-resistant cultivars harboured partial deletions or insertions. In a genomic DNA sequence alignment analysis, mutations in intron regions were detected in both Nt MLO genes of powdery mildew-resistant cultivars, and these mutations were linked to the powdery mildew-resistant phenotype. Transgenic Kokubu expressing wildtype Nt MLO1 or Nt MLO2 exhibited severe disease symptoms, the same as those in susceptible cultivars. These results indicate that mutations of intron regions of two Nt MLO genes in powdery mildew resistant cultivar Kokubu trigger the aberrant splicing of MLO transcripts and the subsequent inhibition of functional MLO protein synthesis, and that Nt MLO1 and Nt MLO2 are functionally redundant. [ABSTRACT FROM AUTHOR]

Plain English summary Adults with Fabry disease experience severe challenges, which adversely impact their quality of life (QOL). As it is a rare disease, non-patients lack awareness of the severity of its symptoms and the resultant social difficulties of the patients. Most instruments that measure QOL are not specific enough to address issues related to Fabry disease. Therefore, in this study, a measurement instrument known as the Adult Fabry QOL (AFQOL) scale was designed and validated. The 39-item scale covers five domains that are congruent with the symptoms of adult Fabry disease. It differs from other QOL scales as it also assesses the impact of work and personal relationships on patients’ QOL and symptoms that progress in adulthood. This study has important implications for healthcare providers who treat adult patients with Fabry disease, enabling them to have a fuller picture of the unique needs of this population.

Protein aggregation is a hallmark of many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Although mutations in TARDBP, encoding transactive response DNA-binding protein 43 kDa (TDP-43), account for less than 1% of all ALS cases, TDP-43–positive aggregates are present in nearly all ALS patients, including patients with sporadic ALS (sALS) or carrying other familial ALS–causing (fALS-causing) mutations. Interestingly, TDP-43 inclusions are also present in subsets of patients with frontotemporal dementia, Alzheimer’s disease, and Parkinson’s disease; therefore, methods of activating intracellular protein quality control machinery capable of clearing toxic cytoplasmic TDP-43 species may alleviate disease-related phenotypes. Here, we identify a function of nemo-like kinase (Nlk) as a negative regulator of lysosome biogenesis. Genetic or pharmacological reduction of Nlk increased lysosome formation and improved clearance of aggregated TDP-43. Furthermore, Nlk reduction ameliorated pathological, behavioral, and life span deficits in 2 distinct mouse models of TDP-43 proteinopathy. Because many toxic proteins can be cleared through the autophagy/lysosome pathway, targeted reduction of Nlk represents a potential approach to therapy development for multiple neurodegenerative disorders.

Context: Few reports focused on the sex differences in alopecia areata (AA) treated with steroid pulse therapy. Aims: This study aimed to investigate the association between the clinical outcomes and distinction of gender in AA patients treated with steroid pulse therapy. Settings and Design: This study retrospectively investigated 32 cases (15 males and 17 females) treated with steroid pulse therapy at the Department of Dermatology at the Shiga University of Medical Science between September 2010 and March 2017. Methods and Material: The administration of corticosteroid was 500 mg methylprednisolone intravenous infusion for 3 consecutive days. Patients were followed up approximately once a month until March 2017. Statistical Analysis Used: The respective data were analyzed by examining and comparing males and females. Statistical analysis was performed using t-test and χ2 test. Results: There were no significant differences in periods from the onset of AA to the administration of steroid pulse therapy (P = 0.2), the degree of severity (P = 0.37) and improved rate (P = 0.0772) between males and females. In contrast, the remission rate was 20% (3 of 15 males) and 71% (12 of 17 females), which was statistically significant (P = 0.0042). Previous reports have also shown a significant difference in the remission rate between males and females (males: 32 of 114; females: 51 of 117; P = 0.014). Conclusions: Despite the limitations of a small sample size including the previous reports (n = 261), female patients with AA would have better outcomes than male patients after steroid pulse therapy.

This meta-analysis was performed to determine whether an indirect laryngoscope is more advantageous than a direct laryngoscope for tracheal intubation in the setting of a difficult pediatric airway. Data on the intubation failure and intubation time during tracheal intubation were extracted from prospective and retrospective studies identified through a comprehensive literature search. Data from 10 individual articles (11 trials) were combined, and a DerSimonian and Laird random-effects model was used to calculate either the pooled relative risk (RR) or the weighted mean difference (WMD) and the corresponding 95% confidence interval (CI). Meta-analysis of the 10 articles indicated that the intubation failure of tracheal intubation with an indirect laryngoscope was not significantly different from that of a direct laryngoscope in patients with a difficult airway (RR 0.86, 95% CI 0.51–1.46; p = 0.59; Cochrane’s Q = 50.5; I2 = 82%). Intubation time with an indirect laryngoscope was also similar to that with a direct laryngoscope (WMD 4.06 s; 95% CI −1.18–9.30; p = 0.13; Cochrane’s Q 39.8; I2 = 85%). In conclusion, indirect laryngoscopes had the same intubation failure and intubation time as direct laryngoscopes in pediatric patients with a difficult airway. Currently, the benefits of indirect laryngoscopes have not been observed in the setting of a difficult pediatric airway.

BackgroundAs the meningeally derived, fibroblast-rich, mass-produced by intrathecal morphine infusion is not produced by all opiates, but reduced by mast cell stabilizers, the authors hypothesized a role for meningeal mast cell/fibroblast activation. Using the guinea pig, the authors asked: (1) Are intrathecal morphine masses blocked by opiate antagonism?; (2) Do opioid agonists not producing mast cell degranulation or fibroblast activation produce masses?; and (3) Do masses covary with Mas-related G protein-coupled receptor signaling thought to mediate mast cell degranulation?MethodsIn adult male guinea pigs (N = 66), lumbar intrathecal catheters connected to osmotic minipumps (14 days; 0.5 µl/h) were placed to deliver saline or equianalgesic concentrations of morphine sulfate (33 nmol/h), 2',6'-dimethyl tyrosine-(Tyr-D-Arg-Phe-Lys-NH2) (abbreviated as DMT-DALDA; 10 pmol/h; μ agonist) or PZM21 (27 nmol/h; biased μ agonist). A second pump delivered subcutaneous naltrexone (25 µg/h) in some animals. After 14 to 16 days, animals were anesthetized and perfusion-fixed. Drug effects on degranulation of human cultured mast cells, mouse embryonic fibroblast activation/migration/collagen formation, and Mas-related G protein-coupled receptor activation (PRESTO-Tango assays) were determined.ResultsIntrathecal infusion of morphine, DMT-DALDA or PZM21, but not saline, comparably increased thermal thresholds for 7 days. Spinal masses proximal to catheter tip, composed of fibroblast/collagen type I (median: interquartile range, 0 to 4 scale), were produced by morphine (2.3: 2.0 to 3.5) and morphine plus naltrexone (2.5: 1.4 to 3.1), but not vehicle (1.2: 1.1 to 1.5), DMT-DALDA (1.0: 0.6 to 1.3), or PZM21 (0.5: 0.4 to 0.8). Morphine in a naloxone-insensitive fashion, but not PZM21 or DMT-DALDA, resulted in mast cell degranulation and fibroblast proliferation/collagen formation. Morphine-induced fibroblast proliferation, as mast cell degranulation, is blocked by cromolyn. Mas-related G protein-coupled receptor activation was produced by morphine and TAN67 (∂-opioid agonist), but not by PZM21, TRV130 (mu biased ligand), or DMT-DALDA.ConclusionsOpiates that activate Mas-related G protein-coupled receptor will degranulate mast cells, activate fibroblasts, and result in intrathecal mass formation. Results suggest a mechanistically rational path forward to safer intrathecal opioid therapeutics.

Abstract Background The coronal whole-leg radiograph is generally used for preoperative planning in total knee arthroplasty. The distal femoral valgus angle (DFVA) is measured for distal femoral bone resection using an intramedullary guide rod. The effect of coronal and sagittal femoral shaft bowing on DFVA measurement in the presence of malrotation or knee flexion contracture has not been well reported. The objectives of this study were: (1) to investigate the effects of whole-leg malrotation and knee flexion contracture on the DFVA in detail, (2) to determine the additional effect of coronal or sagittal femoral shaft bowing. Methods We studied 100 consecutive varus and 100 valgus knees that underwent total or unicompartmental knee arthroplasty. Preoperative CT scans were used to create digitally reconstructed radiography (DRR) images in neutral rotation (NR, parallel to the surgical epicondylar axis), and at 5° and 10° external rotation (ER) and internal rotation (IR). The images were also reconstructed at 10° femoral flexion. The DFVA was evaluated in each DRR image, and the angular variation due to lower limb malposition was investigated. Results The DFVA increased as the DRR image shifted from IR to ER, and all angles increased further from extension to 10° flexion. The DFVA variation in each position was 1.3° on average. A larger variation than 2° was seen in 12% of all. Multivariate regression analysis showed that sagittal femoral shaft bowing was independently associated with a large variation of DFVA. Receiver operating characteristic analysis showed that more than 12° of sagittal bowing caused the variation. Conclusion If femoral sagittal bowing is more than 12°, close attention should be paid to the lower limb position when taking whole-leg radiographs. Preoperative planning with whole-leg CT data should be considered.

Purpose: This study assessed rotational mismatch between components after total knee arthroplasty (TKA) in the supine and standing positions and aimed to investigate the effect of rotational mismatch in the standing position on postoperative patient‐reported outcome measures (PROMs). Methods: Seventy‐one patients (71 knees) who underwent TKA for medial knee osteoarthritis were used to investigate rotational mismatches between components. Rotational mismatches between components were examined on postoperative standing whole‐leg and supine knee radiographs using a three‐dimensional‐to‐two‐dimensional model image registration technique, and the angles between the reference axes of the components were measured. Component alignment was evaluated using postoperative computed tomography images, and a questionnaire (2011 version of the Knee Society Score: [KSS 2011]) was mailed to investigate postoperative PROMs. Results: In the entire cohort, rotational mismatches in the supine and standing positions were similar (p = 0.9315). In 15% of patients, the mismatch was large (>5°) in the supine position but small (<5°) in the standing position (overestimated group). However, in 23% of patients, the mismatch was small (<5°) in the supine position and large (>5°) in the standing position (underestimated group). The underestimated group had severe preoperative varus deformity, resulting in external rotation of both femoral and tibial components. Rotational mismatch in the standing position (p = 0.0032) was a significant risk factor for unfavourable PROMs. Patients with a mismatch in the standing position had significantly lower scores than those without a mismatch (p = 0.0215), exceeding the minimal clinically important difference values. Conclusions: The underestimated group is clinically important because the surgical procedure and intraoperative assessment of component placement are performed in the supine position. In cases of severe preoperative varus deformity, care should be taken not to place the component in malrotation to avoid rotational mismatch in the standing position. Level of Evidence: Ⅳ, Case series. [ABSTRACT FROM AUTHOR]