Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1

Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.     

Safety and Efficacy of the Moderate Sedation During Flexible Bronchoscopic Procedure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Moderate sedatives have been increasingly used to improve patient comfort during flexible bronchoscopy (FB). However, routine use of moderate sedation during FB is controversial because its efficacy and safety are not well established.This study aims to evaluate the efficacy and safety of moderate sedation during FB.A search was made of Medline, EMBASE, and the Cochrane Library to May 2014.Randomized controlled trials (RCTs) and quasi-RCTs were included.The main analysis was designed to examine the efficacy of moderate sedation during FB in sedation than no-sedation.The willingness to repeat FB was significantly more in sedation than no-sedation (odds ratio [OR] 2.30; 95% confidence interval [CI] 1.11–4.73; P = 0.02; I² = 22.5). The duration of FB was shorter in sedation group than no-sedation group (standardized mean difference [SMD] −0.21; 95% CI −0.38 to −0.03; P = 0.02; I² = 78.3%). Event of hypoxia was not significantly different between sedation and no-sedation groups (OR 0.86; 95% CI 0.42–1.73; P = 0.67; I² = 0%). The SpO₂ during procedure was not different between sedation and no-sedation groups (SMD −0.14; 95% CI −0.37 to 0.08; P = 0.21; I² = 49.9%). However, in subgroup analysis without supplemental oxygen, the SpO₂ was significantly lower in sedation than no-sedation group (SMD −0.45; 95% CI −0.78 to −0.11; P = 0.01; I² = 0.0%).According to this meta-analysis, moderate sedation in FB would be useful in patients who will require repeated bronchoscopies as well as safe in respiratory depression. To our knowledge, although the various sedative drugs are already used in the real field, this analysis was the first attempt to quantify objective results. We anticipate more definite and studies designed to elucidate standardized outcomes for moderate sedation in FB.     

Troubled-Cell Indicator Based on Mean Value Property for Hybrid WENO Schemes

In this paper, we introduce a new type of troubled-cell indicator to improve hybrid weighted essentially non-oscillatory (WENO) schemes for solving the hyperbolic conservation laws. The hybrid WENO schemes selectively adopt the high-order linear upwind scheme or the WENO scheme to avoid the local characteristic decompositions and calculations of the nonlinear weights in smooth regions. Therefore, they can reduce computational cost while maintaining non-oscillatory properties in non-smooth regions. Reliable troubled-cell indicators are essential for efficient hybrid WENO methods. Most of troubled-cell indicators require proper parameters to detect discontinuities precisely, but it is very difficult to determine the parameters automatically. We develop a new troubled-cell indicator derived from the mean value theorem that does not require any variable parameters. Additionally, we investigate the characteristics of indicator variable; one of the conserved properties or the entropy is considered as indicator variable. Detailed numerical tests for 1D and 2D Euler equations are conducted to demonstrate the performance of the proposed indicator. The results with the proposed troubled-cell indicator are in good agreement with pure WENO schemes. Also the new indicator has advantages in the computational cost compared with the other indicators.     

Pseudocystic pilomatricoma: A new variant and review of the literature

A classic pilomatricoma, which usually presents with an asymptomatic, solitary, firm, subcutaneous nodule in the head, neck, or extremities of the paediatric population, is easily diagnosed based on its characteristic clinical and histopathological features. However, its variants often pose particular diagnostic challenges to clinicians due to their rarity and diverse clinicopathological features. We present a new pseudocystic variant, manifesting as solid lesions floating in a fluid‐filled sac.     

Symptomatic perineural cyst after spontaneous subarachnoid hemorrhage: A case report

Rationale:Tarlov or perineurial cysts are nerve root lesions often found in the sacral region. Most perineural cysts (PCs) remain asymptomatic throughout a patient''s life. While their pathogenesis is still unclear, trauma resulting in hemorrhaging into subarachnoid space has been put forward as a possible cause of these cysts. Recently, we worked with a patient experiencing symptomatic PCs after spontaneous subarachnoid hemorrhage.Patient concerns:A 45-year-old man had a coil embolization procedure performed after being diagnosed with a subarachnoid hemorrhage from a ruptured anterior communicating artery. His symptoms were relieved after the procedure, but 7 days later he reported worsening pain in the left perineal area. The pain was intermittent at its onset and exacerbated by sitting, walking, and coughing.Diagnoses:Two weeks after the embolization procedure, a lumbar spine MRI revealed 2 PCs at the S1 and S2 level affecting the left S2 root with high signal intensity in T2 and T1 images, suggestive of bleeding within the cyst.Interventions:We operated using a posterior approach. Cyst fenestration was done after S1 laminectomy. We aspirated approximately 1 cc of old blood.Outcomes:His pain was relieved immediately after cyst removal and no neurologic deterioration occurred during the postoperative period.Lessons:Subarachnoid hemorrhage can be the source of the development of pain from asymptomatic PCs, making them symptomatic. Surgical extirpation is 1 treatment option for these symptomatic PCs.     

Erythema induratum of Bazin in a 10‐year‐old boy

Erythema induratum of Bazin (EIB) is a form of tuberculid resulting from hypersensitivity to tuberculosis antigen. EIB occurs most commonly in middle‐aged women and is not typically seen in children. Here, we present a rare case of EIB, presenting as a chronic nodular panniculitis, in a 10‐year‐old Korean boy.     

Three-dimensional measurement of radiographic bone–implant contact lengths of zygomatic implants in zygomatic bone: a retrospective study of 66 implants in 28 patients

Zygomatic implant treatment is widely applied for severe maxillary atrophy to help rehabilitate the maxillary dentition. This retrospective study was performed to evaluate the actual radiographic bone–implant contact (rBIC) lengths of zygomatic implants. The records of 28 patients who underwent zygomatic implant surgery and subsequent follow-up examinations between August 2013 and September 2018 in the Department of Oral and Maxillofacial Surgery, Taipei Tzu Chi Hospital were reviewed. The surgeries were performed by a single surgeon using the same treatment protocol. All patients had a computed tomography scan at 1 year after the surgery. Using three-dimensional imaging software, an investigator measured the rBIC lengths of 66 implants and documented their clinical status. The implant survival rate was 100%. The mean rBIC length was significantly longer in male patients than in female patients (20.80 ± 5.88 mm versus 17.79 ± 6.34 mm; P = 0.028). The mean rBIC length of double zygomatic implants was significantly longer when compared to that of single implants (21.11 ± 6.23 mm versus 17.75 ± 5.85 mm; P = 0.027). This article is novel in reporting the exact rBIC lengths of zygomatic implants in a clinical setting. The results showed that zygomatic implants are a viable treatment modality for full-mouth rehabilitation.