Hydrostatic pressure mediates epithelial-mesenchymal transition of cholangiocytes through RhoA/ROCK and TGF-ß/smad pathways.

Biomechanical cue within the tissue microenvironment is known to play a critical role in regulating cell behaviors and maintaining tissue homeostasis. As hydrostatic pressure often increases in biliary system under pathological states, we investigated the effect of the moderate elevation of the hydrostatic pressure on biliary epithelial cells, especially on the epithelial-mesenchymal transition (EMT). Human intrahepatic biliary epithelial cells were loaded to hydrostatic pressure using a commercial device. We found that loading the cells to 50 mmHg hydrostatic pressure induced obvious morphological changes and significantly upregulated vimentin, ZEB1, and pSmad2/3, fibronectin, and collagen 1α. All changes induced by hydrostatic pressure loading were effectively mitigated by either ROCK inhibitor (Y-27632) or ALK5 inhibitor (SB-431542). Our in vitro experimental data suggests that hydrostatic pressure loading induces EMT of cholangiocytes through RhoA/ROCK and TGF-ß/Smad pathways. Elevated hydrostatic pressure in biliary duct system under pathological states may promote the biliary epithelial cells shifting to profibrotic and mesenchymal characteristics.

Addressing the Impact of Deep Venous Stenting on the Management of Venous Ulcer.

BACKGROUND: Venous ulcers are a late and severe form of chronic venous insufficiency and account for 70% of all etiologies that cause leg ulcers in the lower limb, and they account for 20% of the 2.5 million cases complaining of chronic venous disease. Our study aims to investigate the effect of venous stenting of the deep veins on the healing of the venous ulcer. METHODS: This is a single-center, retrospective study conducted on prospectively recorded medical records of 78 patients with chronic deep venous diseases-C6 (either nonocclusive iliac venous lesion or post-thrombotic syndrome). Our lesion involved May-Thurner lesions, occlusions, insufficiencies, or stenoses owing to an affection of the venous outflow segment. All our patients underwent endovascular management, and those who did not respond successfully were transitioned to compression therapy. We then compared the outcomes of both groups in terms of ulcer healing and quality of life. RESULTS: A total of 78 patients (78 limbs), with a mean age of 39.6 ± 8.06 (range: 22-60) years, were treated. Fifty-four patients (67.9%) were males, and 24 (32.1%) were female. The etiology was primary nonocclusive iliac venous lesion in 12 limbs (16.2%) and secondary post-thrombotic obstructions in 66 (83.7%). Follow-up of the ulcer with compliance to compression therapy and standard care of the ulcer, sustained ulcer healing (reduction in ulcer area) was achieved in 60% of limbs, and most of the nonocclusive healing occurred within the first 3 months (P < 0.01). CONCLUSIONS: Our results show that deep venous stenting is associated with high wound healing rates. This rate reaches a statistically significant difference in 3 months, but this difference doesn't reach statistical significance at 6 months, with less recurrence and improved quality of life with a high cumulative patency rate, and compression therapy is the mainstay of the conservative management of venous ulceration.

Morphological changes in intraepithelial and stromal telocytes in Cyprinus carpio in response to salinity stress.

Telocytes establish connections and communicate with various types of cells and structures. Few experimental studies have been performed on telocytes. In this study, we investigated the effect of salinity stress on telocytes in relation to osmoregulatory, immune, and stem cells. After exposing the common carp to 0.2 (control), 6, 10, or 14 ppt salinity, we extracted and fixed gill samples in glutaraldehyde, processed and embedded the samples in resin, and prepared semi-thin and ultrathin sections. Two types of telocytes were identified: intraepithelial and stromal telocytes. Intraepithelial telocytes were found to form part of the cellular lining of the lymphatic space and shed secretory vesicles into this space. Stromal telocytes were observed to shed their secretory vesicles into the secondary circulatory vessels. Both intraepithelial and stromal telocytes were enlarged and exhibited increased secretory activities as salinity increased. They exerted their effects via direct contact and paracrine signaling. The following changes were observed in samples from fish exposed to high salinity levels: chloride cells underwent hypertrophy, and their mitochondria became cigar-shaped; pavement cells were enlarged, and their micro-ridges became thin and elongated; stromal telocytes established contact with stem cells and skeletal myoblasts; skeletal muscle cells underwent hypertrophy; and macrophages and rodlet cells increased in number. In conclusion, our findings indicate that intraepithelial and stromal telocytes respond to salinity stress by activating cellular signaling and that they play major roles in osmoregulation, immunity, and regeneration.

Negative pressure induces dedifferentiation of hepatocytes via RhoA/ROCK pathway.

Biomechanical forces are known to regulate the biological behaviors of cells. Although negative pressure has been used for wound healing, it is still unknown about its role in regulating cell plasticity. We investigated whether negative pressure could induce the dedifferentiation of hepatocytes. Using a commercial device, we found that the exposure of primary human hepatocytes to -50 mmHg quickly induced the formation of stress fibers and obviously changed cell morphology in 72 h. Moreover, the exposure of hepatocytes to -50 mmHg significantly upregulated RhoA, ROCK1, and ROCK2 in 1-6 h, and dramatically enhanced the expression of marker molecules on "stemness", such as OCT4, SOX2, KLF4, MYC, NANOG, and CD133 in 6-72 h. However, all these changes in hepatocytes induced by -50 mmHg stimulation were almost abrogated by ROCK inhibitor Y27623. Our data suggest that an appropriate force of negative pressure stimulation can effectively induce the dedifferentiation of hepatocytes via RhoA/ROCK pathway activation.

Mental health research in the Arab region in response to the COVID-19 pandemic: a scoping review.

Background: The ongoing pandemic has led to a global surge in coronavirus disease 2019 (COVID-19)-related mental health research. However, most related publications come from Western countries or China, and their findings cannot always be extrapolated to Arab countries. Aims: This study provides a quantitative and qualitative analysis of mental health research pertaining to Arab countries' response to the COVID-19 pandemic. Methods: A scoping review of the World Health Organization (WHO) COVID-19 database for publications on mental health was conducted by authors affiliated with Arab institutions, including articles from inception to 24 October 2020. The included publications were evaluated for their national distribution, international collaboration, publication type, and main research themes. Methodological quality analysis of the included research studies was performed using the original and modified versions of the Newcastle-Ottawa Scale. Results: In total, 102 articles were included in this study, averaging 4.6 articles per Arab country. Most of the articles emerged from the Kingdom of Saudi Arabia, Jordan, and Egypt. A majority of publications demonstrated international collaboration. Most of the publications were original research studies and cross-sectional in design. The predominant research theme was examining the pandemic's mental health effects on the general population and healthcare workers. Only 28.0% of the studies were of high methodological quality, whereas 41.5% were moderate and 30.5% were low in quality. Conclusions: Mental health research in response to the COVID-19 pandemic in the Arab region has quantitative and qualitative shortfalls. Arab institutions need to respond to the pandemic promptly in order to address the delineated research gap and to generate higher-quality research output.

Hydrostatic pressure induces profibrotic properties in hepatic stellate cells via the RhoA/ROCK signaling pathway.

Elevated interstitial fluid hydrostatic pressure is commonly observed in diseased livers. We herein examined the hypothesis that hydrostatic pressure induces hepatic stellate cells to acquire profibrotic properties under pathological conditions. Human hepatic stellate cells were exposed to 50 mmHg pressure for 24 h. Although we observed few changes of cell growth and morphology, PCR array data on the expression of fibrosis-associated genes suggested the acquisition of profibrotic properties. The exposure of hepatic stellate cells to 50 mmHg pressure for 24 h also significantly enhanced the expression of RhoA, ROCK1, α-SMA, TGF-ß1 , p-MLC, and p-Smad2, and this was effectively attenuated by the ROCK inhibitor Y-27632. Our ex vivo experimental data suggest that elevated interstitial fluid hydrostatic pressure under pathological conditions may promote liver fibrosis by inducing acquisition of profibrotic properties of hepatic stellate cells through the RhoA/ROCK signaling pathway.

Angiotensin receptor blocker alleviates liver fibrosis by altering the mechanotransduction properties of hepatic stellate cells.

Angiotensin receptor blockers have been reported to be beneficial to liver fibrosis, but the relevant molecular and cellular mechanisms remain unclear. We herein investigated whether low-dose angiotensin receptor blocker alleviated liver fibrosis through mechanotransduction regulation. Hydrostatic pressure-induced liver fibrosis model was established in mice by ligating partially the inferior vena cava, and then randomly received a very low dose of losartan (0.5 mg/kg) or placebo treatment for 8 weeks. We found that losartan administration interfered the expression of several mechanotransductive molecules, and effectively alleviated liver fibrosis. Using a commercial device, we further confirmed that ex vivo loading of hepatic stellate cells to 50 mmHg hydrostatic pressure for 24 h significantly upregulated RhoA, ROCK, AT1R, and p-MLC2, which was effectively attenuated by adding 10 nM losartan in medium. Our in vivo and ex vivo experimental data suggest that low-dose angiotensin receptor blockers may alleviate hydrostatic pressure-induced liver fibrosis by altering the mechanotransduction properties of hepatic stellate cells.NEW & NOTEWORTHY Our ex vivo and in vivo experiments clearly indicated that low-dose losartan alleviated liver fibrosis, likely by modulating the mechanotransduction properties of HSCs. Uncovering the biomechanical signaling pathway of ARB treatment on liver fibrosis will be helpful to develop novel molecular targeting therapy for liver diseases.

Developmental morphological analyses on the preglottal salivary gland in Japanese quails (Coturnix japonica).

To understand the development of the mucous preglottal salivary gland in Coturnix japonica (Japanese quail), morphological and histochemical studies were performed on 20 healthy Japanese quail embryos (aging from 10th to 17th incubation days) and 25 healthy quail chicks (aging from 0th to 60th days). The primordia of preglottal salivary gland were observed as an epithelial bud at the early embryonic stage, which then elongated and differentiated into secretory units by the end of this stage. In Japanese quails, the preglottal salivary gland was a mucous polystomatic tubuloalveolar unpaired gland composed of two lateral portions and a middle one embedded into the submucosa of the lingual root. The gland openings accompanied taste pore (8.17 µm) of taste buds associated salivary glands type; some skeletal muscle fibers embedded among secretory lobules extended from muscle cricohyoideus at 14th day-old quail chick. Also, both herbts corpuscles and secretory motor plexus could be detected among secretory lobules. Based on our investigations, the development of the preglottal salivary gland could clearly be distinguished in the embryonic stage into pre bud and bud stages at 10th day old, cord and branching stages ended by cavitation at 11th day old, canalization stage at 13th day old, lobulation and secretory stages by the 17th day old. The secretory materials showed different histochemical reactions ended with highly alcinophilic mucous indicated highly sialomucin (acidic) content. Myoepithelial cells could be demonstrated at a 17-day old quail embryo and thereafter surrounded the secretory endpieces of the preglottal salivary gland.

Small bowel obstruction and ileocolic fistula caused by post-myomectomy Gossypiboma transmural migration: A case report and review of the literature.

INTRODUCTION: Post-myomectomy Gossypiboma causing Ileo-colic fistula is tremendously rare; it may present as a tumor and stand a diagnostic challenge. The duration between the primary procedure and the presentation is unpredictable. CASE PRESENTATION: A 37-year-old Sudanese/African woman presented with a 4-month history of left iliac fossa mass, pain, anorexia, and persistent, recurrent vomiting with episodes of diarrhea during the last month PTP. She had two gynecological surgeries. Abdominal X-ray & abdominopelvic CECT showed a left iliac fossa pelvic-abdominal collection, distal small bowel partial obstruction, and contrast passage from the small bowel to the sigmoid colon. Diagnosis retained foreign body with abscess causing distal ileal subacute obstruction and an ileo-sigmoid fistula. Surgical exploration, extraction of Gossypiboma with small bowel resection, primary sigmoid colon repair, and a protective transverse colon stoma were done. Six weeks later, colostomy closed after distal loopogram and flexible-sigmoidoscopy. CLINICAL DISCUSSION: A missed intraperitoneal gauze is the top differential diagnosis in patients presenting with acute abdomen after recent abdominal surgery. Transmural migration is slow but leads to difficult clinical situations, peritonitis, or fistulas. Our case reflects the light on the importance of the golden rule of perioperative gauze count and documentation. Thus, minimizing the surgical complications and preventing severe postoperative morbidities. CONCLUSION: Entero-colic fistula due to trans mural migration is not frequently encountered, and its complications can lead to morbidities and even mortality if not promptly diagnosed and treated. Strict adherence to the golden rule of counting and prevent such life-threatening complications and improves patients' safety.

Three-year results of a randomized controlled trial comparing mechanochemical and thermal ablation in the treatment of insufficient great saphenous veins.

OBJECTIVE: Mechanochemical ablation (MOCA) is a nonthermal nontumescent method of treating saphenous vein insufficiency. The feasibility and short-term results of MOCA are good, but its long-term results are unknown. A randomized study was performed to compare MOCA with endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) in the setting of unilateral great saphenous vein (GSV) insufficiency. METHODS: Venous outpatient clinic patients with varicose veins (CEAP class C2-C4) caused by GSV insufficiency were invited to participate in the study; in total, 132 patients met the inclusion criteria and were willing to participate. Patients were randomized to treatment (2:1:1 for MOCA, EVLA, and RFA, respectively). The state of the GSV with duplex Doppler ultrasound examination and the disease-specific quality of life were assessed at 1 month, 1 year, and 3 years after the treatment. RESULTS: Some patients declined to continue in the study after randomization; in total, 117 patients underwent treatment. At 3 years, the occlusion rate was significantly lower with MOCA than with either EVLA or RFA (82% vs 100%; P = .005). Quality of life was similar between the groups. In the MOCA group, GSVs that were larger than 7 mm in diameter preoperatively were more likely to recanalize during the follow-up period. The partial recanalizations of proximal GSV observed at 1 year progressed during the follow-up. CONCLUSIONS: MOCA is a feasible treatment option in an outpatient setting, but its technical success rates are inferior compared with endovenous thermal ablation. Its use in large-caliber veins should be considered carefully.

Catheter-Directed Thrombolysis Versus Pharmacomechanical Thrombectomy for Upper Extremity Deep Venous Thrombosis: A Cost-Effectiveness Analysis.

BACKGROUND: Upper extremity deep vein thrombosis represents (UEDVT) 2-3% of all deep vein thrombosis. Catheter directed thrombolysis (CDT) was replaced largely by pharmacomechanical thrombolysis (PMT) in our institution. In this study we compared the immediate and 1-year results as well as the total hospital costs between CDT and PMT in the treatment of UEDVT. METHODS: From 2006 to 2013, 55 patients with UEDVT were treated with either CDT or PMT at Helsinki University Hospital. Of them, 43 underwent thoracoscopic rib resection later to relieve phlebography-confirmed vein compression. This patient cohort was prospectively followed up with repeated phlebographies. CDT was performed to 24 patients, and 19 had PMT with a Trellis™ device. Clinical evaluation and vein patency assessment were performed with either phlebography or ultrasound 1 year after the thrombolysis. Primary outcomes were immediate technical success, 1-year vein patency, and costs of the initial treatment. RESULTS: The immediate overall technical success rate, defined as recanalization of the occluded vein and removal of the fresh thrombus, was 91.7% in the CDT group and 100% in the PMT group (n.s.). The median thrombolytic time was significantly longer in CDT patients than that in PMT patients (21.1 vs. 0.33 hr, P < 0.00001). There were no procedure-related complications. The 1-year primary assisted patency rate was similar in both the groups (91.7% and 94.7%). There were no recurrences of clinical DVT. The hospital costs for the acute period were significantly lower in the PMT group than those in the CDT group (medians: 11,476 € and 5,975 € in the CDT and PMT groups, respectively [P < 0.00001]). CONCLUSIONS: The clinical results of the treatment of UEDVT with CDT or PMT were similar. However, PMT required shorter hospital stay and less intensive surveillance, leading to lower total costs.

Treatment of Paget-Schroetter syndrome with a three-stage approach including thoracoscopic rib resection at the second stage.

OBJECTIVE: Young, active persons may suffer lifelong consequences of subclavian vein thrombosis, but the best treatment options remain unclear. On introduction of more active pharmacomechanical thrombus removal and thoracoscopic rib resection in our institution, we planned a diagnostic and treatment protocol and aimed to analyze the early, midterm, and intermediate-term results. METHODS: The study included 72 patients who were diagnosed with an upper limb deep venous thrombosis and underwent phlebography between 2006 and 2013. After the initial treatment, control phlebography was performed and a thoracoscopic first rib resection was considered. Postoperative balloon angioplasty was performed when appropriate, and 1-year follow-up phlebography was carried out. RESULTS: After the initial thrombus removal, 60 patients were treated with thoracoscopic first rib resection and subsequent phlebography with or without balloon angioplasty. The median time from symptom to surgery was 124 days, and six (10%) patients had a reocclusion before surgery. Ten (16.7%) patients experienced complications, which were treated mainly with a chest tube (n = 3) or thoracoscopic re-exploration (n = 4). Three months after surgery, 98.3% (59/60) experienced an overall relief of symptoms. No recurrence of clinical thrombosis or residual compression due to incomplete rib resection was seen, and 96.6% (56/58) of the patients reported an overall improvement of symptoms at 13 months. Two patients (3.4%) were treated for chronic pain and had electroneuromyography-verified nerve plexus damage. In both cases, the pain was relieved in the long run. CONCLUSIONS: A combination of early thrombus removal, thoracoscopic first rib resection, and postoperative venous balloon angioplasty seems to yield acceptable intermediate-term results after Paget-Schroetter thrombosis.

Efficacy of endovascular treatment for pelvic congestion syndrome.

BACKGROUND: Chronic pelvic pain is not a rare health problem among women. One of the most common causes of chronic pelvic pain is pelvic congestion syndrome (PCS). We have reviewed all medical literature on the endovascular treatment of PCS and hereby provide a brief overview of the anatomy, pathophysiology, and clinical aspects of ovarian and pelvic varices. We describe the technique of transcatheter embolization, the complications thereof and the clinical results of the treatment. METHODS: A literature search was performed using PubMed, Science Direct, Google Scholar, and Scopus to identify case series on the endovascular treatment of PCS up until the end of November 2014. RESULTS: Twenty studies with a total of 1081 patients were included in the review. There were no randomized trials, and only one study included a control group. The immediate technical success rate in the occlusion of the affected veins was 99%. Seventeen studies reported the 1- to 3-month clinical success of 641 patients. Of these, 88.1% reported moderate to significant relief in the symptoms and 11.9% reported little or no relief. In 17 studies, long-term results were reported, and the follow-up varied between 7.3 months and 5 years. In late follow-up, 86.6% reported relief of the symptoms and 13.6% experienced little or no relief. CONCLUSIONS: The immediate success rate for the endovascular treatment of PCS is good and the complication rate low. Most patients report relief in the symptoms for up to 5 years after the procedure. However, there are no randomized or high-quality controlled trials, and the level of evidence therefore remains at C.