Treatment with YIGSR peptide ameliorates mouse tail lymphedema by 67 kDa laminin receptor (67LR)-dependent cell-cell adhesion.

Impaired microcirculation can cause lymphatic leakage which leads to a chronic swelling in the tissues of the body. However, no successful treatment gives any protection against lymphedema due to the lack of well-revealed pathophysiology of secondary lymphedema. Binary image of laminin immunohistochemical expression revealed that distribution of laminin expression localized during surgically induced lymphedema. 67 kDa laminin receptor (67LR) mRNA expression showed a peak at during lymphedema exacerbation. Since the response of 67LR molecules may affect the prevention of inflammation and edema, here we have hypothesized that 67LR ligand of YIGSR peptide could permit reconstructive environment for amelioration of lymphedema and evaluated the effect of YIGSR in a mouse tail model of lymphedema. Indeed, intra-abdominal injections of YIGSR for the first 3 days after inducing lymphedema in the mouse tail model reduced the tail lymphedema on day 14 by 27% (P = 0.035). Histology showed that YIGSR treatment protected lymphedema impairment in epidermis and dermis, and it also inhibited the expansion of intercellular spaces and enhanced especially cell adhesion in the basement membrane as revealed by transmission electron microscopy. Interestingly, the treatment also reduced the local expression of transforming growth factor (TGF)ß. Further elucidation of the mechanisms of 67LR-facilitated lymphangiogenesis contributes to find potential targets for the treatment of lymphedema.

Supermicrovascular anastomosis training using chicken wings and colored water.

Plastic surgeons require experience in supermicroscopic vascular anastomosis. Herein, we report a simple, rapid, and cost-effective training method using chicken wings and colored water. The avian ventral metacarpal artery was selected for dissection and anastomosis to mimic supermicrosurgery. Over 14 weeks (one anastomosis per day), the ulnar artery in 100 chicken wings was exposed by dissection, cut proximally, and injected with blue food dye-colored water by an inexperienced surgeon. After ligating the artery branches, it was cut and subjected to end-to-end anastomosis. Next, colored water was injected into the ulnar artery to check for suture sufficiency. The vessel was re-dissected to inspect the lumen and sutures qualitatively. Of the 100 wings, the first and last 20 wings' ventral metacarpal artery dissection, anastomosis times, and leakage frequency were compared. Avian ventral metacarpal artery diameter was recorded, and the cumulative anastomosis time where individual anastomosis times started decreasing was determined. Leakage rates before and after this point were compared. The avian ventral metacarpal artery diameter was 0.7-0.8 mm. The last 20 wings had significantly shorter median dissection times (12:27 vs. 17:45 min), anastomosis times (9:02 vs. 12:29 min), and leakage rates (15% vs. 70%); more even stitching and parallel ligature points; and less vessel layer inversion than the first 20 wings. After a cumulative anastomosis time of 10 h 26 min, individual times sharply decreased, and the leakage rate decreased significantly (58.3% vs. 23.8%). The proposed method significantly improved supermicrosurgical anastomosis. Thus, we believe that this method will help surgeons improve their supermicrosurgical skills.

Incidence and risk factors for hospital-acquired cholecystitis.

BACKGROUND: Acute cholecystitis can occur both inside and outside hospital settings. However, little is known about the clinical characteristics of hospital-acquired cholecystitis (HAC). AIM: To investigate the clinical characteristics of HAC in a tertiary academic hospital. METHODS: This retrospective cohort study included hospitalized patients who were found to have gallstones without cholecystitis or cholangitis on admission between January 2018 and December 2021. Multi-variate logistic regression analysis was used to make comparisons between patients with and without HAC. FINDINGS: In total, 890 patients met the inclusion criteria and were evaluated in this study. Forty-one patients (4.6%) developed HAC during the study period. Multi-variate logistic regression analysis showed that a history of cholecystitis or cholangitis, fasting for ≥1 day, and gallstones in the gallbladder neck were independently associated with increased risk of HAC. HAC occurred most frequently after several weeks of admission, and only four patients (9.8%) had bacteraemia. CONCLUSIONS: HAC was relatively common among hospitalized patients. Physicians should be aware of the possibility of HAC in symptomatic hospitalized patients with certain risk factors.

Investigation of Physiological Swelling on Conductivity Distribution in Lower Leg Subcutaneous Tissue by Electrical Impedance Tomography.

There is a strong need for a non-invasive measurement technique that is capable of accurately identifying the physiological condition change or heterogeneity of subcutaneous adipose tissue (SAT) by localizing the abnormalities within the compartment. This paper aims to investigate the feasibility of Electrical Impedance Tomography (EIT) to assess the interstitial fluid in subcutaneous adipose tissue as an enhancement method of bioelectrical impedance spectroscopy (BIS). Here, we demonstrate the preliminary result of EIT with a wearable 16 electrodes sensor. The image-based reference EIT with fat weighted threshold method is proposed. In order to evaluate the performance of our novel method, a physiological swelling experiment is conducted, and Multi-Frequency Bioelectrical Impedance Analysis (MFBIA) is also applied as a comparison with EIT results. The experimental results showed that the proposed method was able to distinguish the physiological swelling condition and effectively to remove the unexpected background noise. Furthermore, the conductivity variation in the subcutaneous layer had a good correlation with extracellular water volume change from MFBIA data; the correlation coefficient R2 = 0.927. It is concluded that the proposed method provides a significant prospect for SAT assessment.

Effect of augmented datasets on deep convolutional neural networks applied to chest radiographs.

AIM: To evaluate the effect of augmented training datasets in a deep convolutional neural network (DCNN) used for detecting abnormal chest radiographs. MATERIALS AND METHODS: Chest radiographs were corrected to conform to a DCNN dataset, with 288 abnormal and 447 normal radiographs. The radiographic images were divided into training and validation sets (441, 60%), and a test set (294, 40%). The training and validation sets were augmented to generate a total of 12,789 training and validation images. The augmentation consisted of operations such as rotation, horizontal and vertical flipping, Gaussian blur, and brightness variation, either alone or combined. The DCNN performed binary classification of the images as being abnormal or normal chest radiographs, and accuracy was used as measure to assess the model performance. RESULTS: The accuracy of the DCNN trained with the augmented dataset tended to be higher than that of the DCNN trained with the non-augmented dataset. The augmented datasets combining rotation and horizontal flipping had a high accuracy of 0.91, showing the highest accuracy among the applied augmentation techniques and combinations. CONCLUSION: Augmentation of training datasets can improve the performance of DCNN for radiographic image classification depending on the applied augmentation technique.

Diagnostic capability of feature-tracking cardiovascular magnetic resonance to detect infarcted segments: a comparison with tagged magnetic resonance and wall thickening analysis.

AIM: To examine the diagnostic capabilities of feature-tracking cardiovascular magnetic resonance (FT-CMR), tagged cine magnetic resonance (MR), and wall thickening (WT) analyses to detect infarcted segments in patients with established myocardial infarction (MI). MATERIALS AND METHODS: Twenty patients with established MI were selected retrospectively and the peak endocardial circumferential strain (CS) was quantified based on the 16-segment model. According to CMR with late gadolinium enhancement, segments were categorised as transmural MI, subendocardial MI, and no MI. RESULTS: A total of 320 segments (62 transmural MI, 50 subendocardial MI, and 208 no MI) were analysed. Peak endocardial CS was significantly lower for transmural MI compared with subendocardial MI (p<0.05) and no MI (p<0.001). Cut-off values of -11.2% for CS by FTCMR, -10.9% for CS by tagged MR, and 23.8% for %WT, differentiated between infarcted and non-infarcted segments with a sensitivity of 72%, 71%, and 56%; specificity of 71%, 75%, and 67%; accuracy of 72%, 73%, and 63%; positive predictive value of 57%, 60%, and 48%; negative predictive value of 83%, 83%, and 74%; and an area-under-the-curve of 0.77, 0.79, and 0.64, respectively. CONCLUSIONS: FT-CMR was diagnostically superior to %WT, and could differentiate between subendocardial and transmural MI. Unlike tagged MR, FT-CMR did not require the acquisition of additional sequences.

Endothelial dysfunction and mechanobiology in pathological cutaneous scarring: lessons learned from soft tissue fibrosis.

Hypertrophic scars/keloids are pathogenic scars that are characterized by collagen and fibroblast accumulation. The endothelia in the lesions are mechanosensitive and participate actively in the pathogenesis of these scars. The present review summarizes how endothelium responds to mechanical stimuli such as shear, stretch and hydrostatic pressure. It also shows that in heart, liver, kidney and lung fibrosis, endothelial dysfunctions (EDs) associate with changes in vascular tone, endothelial permeability, coagulation and vasomodulation that result in inflammation, hypertension and coagulation. Pathological scars exhibit similar EDs during their development and progression. Mechanopharmaceutical or mechanotherapeutic interventions that rescue EDs may be useful scar treatments.

A deskilling and challenging journey: the lived experience of Indonesian nurse returnees.

AIM: To illuminate the lived experiences of Indonesian nurses who previously worked as caregivers in Japanese residential care facilities, by exploring the journey of becoming returnees. BACKGROUND: The creation of bilateral agreements between Indonesia and Japan has facilitated the movement of Indonesian nurses to work as caregivers in Japan since 2008. While this decision raised concerns with regard to the degradation of nursing skills, little is known about this issue from the perspective of nurse returnees and how the experience affects their life. METHOD: A hermeneutic phenomenological method was employed for this study. A purposive sample of 15 Indonesian nurse returnees participated in this study. Semi-structured interviews were conducted in four of Indonesia's provinces between August and October 2015. Data were analysed thematically, supported by QSR NVIVO 10 software. FINDINGS: Four key themes emerged from the data analysis: (i) returning home; (ii) going back to zero; (iii) walking through a difficult journey; and (iv) overcoming barriers. These findings described the lived experiences of nurse returnees when they got back to the country of origin. CONCLUSION: Indonesian nurse returnees experienced deskilling and struggled to re-enter the nursing profession or to find other non-nursing jobs. The significant impact of this migration on individual nurses with regard to maximizing the benefits of return migration deserves further investigation. IMPLICATION FOR NURSING AND HEALTH POLICY: The Indonesian government, jointly with other stakeholders, should develop a brain gain strategy to align returnees' expertise with the needs of the national labour market. The public-private partnership should be strengthened to utilize returnees in healthcare services.

Activating GNAS and KRAS mutations in gastric foveolar metaplasia, gastric heterotopia, and adenocarcinoma of the duodenum.

BACKGROUND: Heterotopic gastric-type epithelium, including gastric foveolar metaplasia (GFM) and gastric heterotopia (GH), is a common finding in duodenal biopsy specimens; however, there is still controversy regarding their histogenetic backgrounds. METHODS: We analysed a total of 177 duodenal lesions, including 66 GFM lesions, 81 GH lesions, and 30 adenocarcinomas, for the presence of GNAS, KRAS, and BRAF mutations. RESULTS: Activating GNAS mutations were identified in 27 GFM lesions (41%) and 23 GH lesions (28%). The KRAS mutations were found in 17 GFM lesions (26%) and 2 GH lesions (2%). A BRAF mutation was found in only one GFM lesion (2%). These mutations were absent in all 32 normal duodenal mucosa specimens that were examined, suggesting a somatic nature. Among the GFM lesions, GNAS mutations were more common in lesions without active inflammation. Analyses of adenocarcinomas identified GNAS and KRAS mutations in 5 (17%) and 11 lesions (37%), respectively. Immunohistochemically, all the GNAS-mutated adenocarcinomas diffusely expressed MUC5AC, indicating gastric epithelial differentiation. CONCLUSIONS: A significant proportion of GFM and GH harbours GNAS and/or KRAS mutations. The common presence of these mutations in duodenal adenoma and adenocarcinoma with a gastric epithelial phenotype implies that GFM and GH might be precursors of these tumours.

Frequent MED12 mutations in phyllodes tumours of the breast.

BACKGROUND: Phyllodes tumours are rare fibroepithelial tumours of the breast, that include benign, borderline, and malignant lesions. Although the molecular basis of phyllodes tumours largely remains unknown, a recent exome study identified MED12 mutations as a sole recurrent genetic alteration in fibroadenoma, a common benign fibroepithelial tumour that shares some histological features with the phyllodes tumour. METHODS: Forty-six phyllodes tumours and 58 fibroadenomas of the breast were analysed for MED12 mutations by using Sanger sequencing. RESULTS: MED12 mutations were identified in 37 out of the 46 phyllodes tumours (80%). The prevalence of MED12 mutations was similar among benign (15/18, 83%), borderline (12/15, 80%), and malignant tumours (10/13, 77%). MED12 mutations were also identified in 36 of the 58 fibroadenomas (62%). The mutations were frequent among intracanalicular-type (24/32, 75%) and complex-type lesions (4/6, 67%), but were significantly less common among the pericanalicular-type lesions (8/20, 40%). A microdissection-based analysis showed that MED12 mutations were confined to the stromal components in both phyllodes tumours and fibroadenomas. CONCLUSIONS: MED12 mutations were frequent among the phyllodes tumours of the breast, regardless of the tumour grade. Phyllodes tumours and fibroadenomas share, at least in part, a common genetic background.

Predictive performance of three practical approaches for grapefruit juice-induced 2-fold or greater increases in AUC of concomitantly administered drugs.

WHAT IS KNOWN AND OBJECTIVE: Clinical pharmacists have a challenging task when answering patients' question about whether they can take specific drugs with grapefruit juice (GFJ) without risk of drug interaction. To identify the most practicable method for predicting clinically relevant changes in plasma concentrations of orally administered drugs caused by the ingestion of GFJ, we compared the predictive performance of three methods using data obtained from the literature. METHODS: We undertook a systematic search of drug interactions associated with GFJ using MEDLINE and the Metabolism & Transport Drug Interaction Database (DIDB version 4.0). We considered an elevation of the area under the plasma concentration-time curve (AUC) of 2 or greater relative to the control value [AUC ratio (AUCR) ≥ 2.0] as a clinically significant interaction. RESULTS AND DISCUSSION: The data from 74 drugs (194 data sets) were analysed. When the reported information of CYP3A involvement in the metabolism of a drug of interest was adopted as a predictive criterion for GFJ-drug interaction, the performance assessed by positive predictive value (PPV) was low (0.26), but that assessed by negative predictive value (NPV) and sensitivity was high (1.00 for both). When the reported oral bioavailability of ≤ 0.1 was used as a criterion, the PPV improved to 0.50 with an acceptable NPV of 0.81, but sensitivity was reduced to 0.21. When the reported AUCR was ≥ 10 after co-administration of a typical CYP3A inhibitor, the corresponding values were 0.64, 0.79 and 0.19, respectively. WHAT IS NEW AND CONCLUSION: We consider that an oral bioavailability of ≤ 0.1 or an AUCR of ≥ 10 caused by a CYP3A inhibitor of a drug of interest may be a practical prediction criterion for avoiding significant interactions with GFJ. Information about the involvement of CYP3A in their metabolism should also be taken into account for drugs with narrow therapeutic ranges.

NOTCH1 expression predicts patient prognosis in esophageal squamous cell cancer.

PURPOSE: The prognosis of patients with esophageal cancer remains poor, and the classification of tumor node metastasis has proven insufficient to predict patient prognosis. Therefore, novel predictive markers of esophageal cancer prognosis are needed. Notch receptors and their ligands have been reported to be upregulated in cervical, lung, colon, renal, and pancreatic cancers, but NOTCH1 expression has not been studied in esophageal cancer. METHODS: Expression of NOTCH1 was quantified by real-time reverse transcription-polymerase chain reaction in 55 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We then examined the correlations between NOTCH1 expression, clinicopathological factors, and prognosis in patients with ESCC. RESULTS: The probability of overall survival was significantly lower for patients with high NOTCH1 expression (p = 0.0028; log-rank test). Overexpression of NOTCH1 was identified as a significant and independent prognostic factor (p = 0.0061) in patients who had undergone surgical treatment for ESCCs. The hazard ratio for predicting early death was 4.298 (95% confidence interval 1.515-12.195) for high versus low NOTCH1 expression. CONCLUSIONS: Our data indicate that NOTCH1 may be a candidate molecular prognostic marker and a molecular target for the development of an effective therapeutic intervention for patients with ESCC.

Role of mechanical forces in hand nail configuration asymmetry in hemiplegia: an analysis of four hundred thumb nails.

OBJECTIVE: To assess the relationship between nail configuration and mechanical force, the nail morphology and pinch strengths of the paralyzed and non-paralyzed sides of patients with hemiplegia were measured. METHODS: Study 1: Analysis of nail configuration. Both thumb nails of 100 subjects with hemiplegia and 100 healthy volunteers (400 thumb nails) were enrolled. The left and right thumb nails were compared in terms of configuration, namely the curve index (defined as nail height/width). Study 2: Measurement of pinch strength. In 10 subjects with hemiplegia and 10 healthy volunteers, the pinch strengths of both sides were compared. RESULTS: Study 1: In the subjects with hemiplegia, the palsy side had a significantly higher curve index than the non-palsy side (32.7 ± 8.3 vs. 24.4 ± 6.5%). The two sides of the healthy volunteers did not differ significantly in terms of the curve index. Study 2: In all hemiplegia cases, the non-palsy side had a higher pinch strength. The differences were statistically significant (4.40 ± 1.90 vs. 0.05 ± 0.16 kg). In the healthy volunteers, the dominant and non-dominant sides did not differ significantly. CONCLUSION: Mechanical forces may affect the nail configuration and could participate in the pathophysiology of nail deformities.

Frequent GNAS mutations in low-grade appendiceal mucinous neoplasms.

BACKGROUND: The molecular basis for the development of appendiceal mucinous tumours, which can be a cause of pseudomyxoma peritonei, remains largely unknown. METHODS: Thirty-five appendiceal mucinous neoplasms were analysed for GNAS and KRAS mutations. A functional analysis of mutant GNAS was performed using a colorectal cancer cell line. RESULTS: A mutational analysis identified activating GNAS mutations in 16 of 32 low-grade appendiceal mucinous neoplasms (LAMNs) but in none of three mucinous adenocarcinomas (MACs). KRAS mutations were found in 30 LAMNs and in all MACs. We additionally analysed a total of 186 extra-appendiceal mucinous tumours and found that GNAS mutations were highly prevalent in intraductal papillary mucinous tumours of the pancreas (88%) but were rare or absent in mucinous tumours of the colorectum, ovary, lung and breast (0-9%). The prevalence of KRAS mutations was quite variable among the tumours. The introduction of the mutant GNAS into a colorectal cancer cell line markedly induced MUC2 and MUC5AC expression, but did not promote cell growth either in vitro or in vivo. CONCLUSION: Activating GNAS mutations are a frequent and characteristic genetic abnormality of LAMN. Mutant GNAS might play a direct role in the prominent mucin production that is a hallmark of LAMN.