Myopericytoma: A Review of Twenty-Three Cases Over Twelve Years and a Case Report of a Rare Neoplasm.

ABSTRACT: Myopericytoma is a rare soft tissue tumor with a predilection for the distal extremities. It is commonly found in the skin and subcutaneous tissues and usually takes a benign course. Current knowledge is limited to isolated case series and reports; hence, this study aims to report our tertiary institution's experience with this uncommon entity. A review of our institution's pathology records for cases of myopericytoma was performed. From January 2009 to September 2020, 23 cases of myopericytoma were identified and their clinicopathologic features were reported. A unique case of myopericytoma of the ankle from the series was also highlighted as a case report. Among the 22 cutaneous cases, 18 were in the extremities and 4 in the head and neck. One patient had an intracranial lesion. Most patients developed asymptomatic nodules (72.2%), but 1 patient had a locally aggressive tumor on presentation. None recurred despite marginal excision in some patients (80.0%). In conclusion, pathologists and surgeons who encounter this rare neoplasm can reassure patients of its benign tendency.

Pulse oximeter as a home assessment tool: Knowledge and user experience among the community in Malaysia during the COVID-19 pandemic

Objective: To determine the degree of knowledge in the usage of pulse oximeter as a home assessment tool among the community in Malaysia. Methods: A cross-sectional survey was conducted in November 2021. The questionnaire assessed the knowledge in using pulse oximeters, user experience and opinions in using pulse oximeter as a home assessment tool during the pandemic. Results: A total of 504 respondents were included in the study, and the mean score in knowledge related to application of pulse oximetry was 73.00%, while the mean score in knowledge related to factors affecting pulse oximetry readings was only 38.51%. A total of 90.5% of the respondents recognised normal pulse rate and 88.5% knew the blood oxygen saturation levels of a healthy adult, while 69.4% recognised the definition of silent hypoxia. In addition, the majority of the respondents agreed that factors such as poor blood circulation (71.2%), excessive movements (69.8%), and hand position (60.7%) affected oximetry readings. However, 61.7%, 81.7%, 77.2% and 76.8% of the respondents could not identify nail polish, skin colour, skin thickness and tattoos as factors that may affect oximetry readings respectively. Conclusions: The respondents showed a satisfactory level of knowledge related to application of pulse oximetry, but a poor level of knowledge related to factors affecting pulse oximetry readings among the community in Malaysia. Continuous efforts in educating the community on the correct use of pulse oximeters are crucial for appropriate home assessment and avoiding unnecessary stress.

Pulse oximeter as a home assessment tool: Knowledge and user experience among the community in Malaysia during the COVID-19 pandemic

Objective: To determine the degree of knowledge in the usage of pulse oximeter as a home assessment tool among the community in Malaysia. Methods: A cross-sectional survey was conducted in November 2021. The questionnaire assessed the knowledge in using pulse oximeters, user experience and opinions in using pulse oximeter as a home assessment tool during the pandemic. Results: A total of 504 respondents were included in the study, and the mean score in knowledge related to application of pulse oximetry was 73.00%, while the mean score in knowledge related to factors affecting pulse oximetry readings was only 38.51%. A total of 90.5% of the respondents recognised normal pulse rate and 88.5% knew the blood oxygen saturation levels of a healthy adult, while 69.4% recognised the definition of silent hypoxia. In addition, the majority of the respondents agreed that factors such as poor blood circulation (71.2%), excessive movements (69.8%), and hand position (60.7%) affected oximetry readings. However, 61.7%, 81.7%, 77.2% and 76.8% of the respondents could not identify nail polish, skin colour, skin thickness and tattoos as factors that may affect oximetry readings respectively. Conclusions: The respondents showed a satisfactory level of knowledge related to application of pulse oximetry, but a poor level of knowledge related to factors affecting pulse oximetry readings among the community in Malaysia. Continuous efforts in educating the community on the correct use of pulse oximeters are crucial for appropriate home assessment and avoiding unnecessary stress.

Single cell analysis reveals multiple requirements for zinc in the mammalian cell cycle.

Zinc is widely recognized as essential for growth and proliferation, yet the mechanisms of how zinc deficiency arrests these processes remain enigmatic. Here we induce subtle zinc perturbations and track asynchronously cycling cells throughout division using fluorescent reporters, high throughput microscopy, and quantitative analysis. Zinc deficiency induces quiescence and resupply stimulates synchronized cell-cycle reentry. Monitoring cells before and after zinc deprivation we found the position of cells within the cell cycle determined whether they either went quiescent or entered another cell cycle but stalled in S-phase. Stalled cells exhibited prolonged S-phase, were defective in DNA synthesis and had increased DNA damage levels, suggesting a role for zinc in maintaining genome integrity. Finally, we demonstrate zinc deficiency-induced quiescence occurs independently of DNA-damage response pathways, and is distinct from mitogen removal and spontaneous quiescence. This suggests a novel pathway to quiescence and reveals essential micronutrients play a role in cell cycle regulation.

Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function.

Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues. Co-culturing human or murine iMacs with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMacs differentiated in vivo into microglia after injection into the brain and into functional alveolar macrophages after engraftment in the lung. Finally, iPSCs from a patient with familial Mediterranean fever differentiated into iMacs with pro-inflammatory characteristics, mimicking the disease phenotype. Altogether, iMacs constitute a source of tissue-resident macrophage precursors that can be used for biological, pathophysiological, and therapeutic studies.

In vitro and in vivo correlates of physiological and neoplastic human Fallopian tube stem cells.

High-grade serous cancer (HGSC) progresses to advanced stages without symptoms and the 5-year survival rate is a dismal 30%. Recent studies of ovaries and Fallopian tubes in patients with BRCA1 or BRCA2 mutations have documented a pre-metastatic intramucosal neoplasm that is found almost exclusively in the Fallopian tube, termed 'serous tubal intraepithelial carcinoma' or STIC. Moreover, other proliferations, termed p53 signatures, secretory cell outgrowths (SCOUTs), and lower-grade serous tubal intraepithelial neoplasms (STINs) fall short of STIC but share similar alterations in expression, in keeping with an underpinning of genomic disturbances involved in, or occurring in parallel with, serous carcinogenesis. To gain insight into the cellular origins of this unique tubal pathway to high-grade serous cancer, we cloned and both immortalized and transformed Fallopian tube stem cells (FTSCs). We demonstrated that pedigrees of FTSCs were capable of multipotent differentiation and that the tumours derived from transformed FTSCs shared the histological and molecular features of HGSC. We also demonstrated that altered expression of some biomarkers seen in transformed FTSCs and HGSCs (stathmin, EZH2, CXCR4, CXCL12, and FOXM1) could be seen as well in immortalized cells and their in vivo counterparts SCOUTs and STINs. Thus, a whole-genome transcriptome analysis comparing FTSCs, immortalized FTSCs, and transformed FTSCs showed a clear molecular progression sequence that is recapitulated by the spectrum of accumulated perturbations characterizing the range of proliferations seen in vivo. Biomarkers unique to STIC relative to normal tubal epithelium provide a basis for novel detection approaches to early HGSC, but must be viewed critically given their potential expression in lesser proliferations. Perturbations shared by both immortalized and transformed FTSCs may provide unique early targets for prevention strategies. Central to these efforts has been the ability to clone and perpetuate multipotent FTSCs.

Long-Term Oncological Safety of Minimally Invasive Hepatectomy in Patients with Hepatocellular Carcinoma: A Case-Control Study

<p><b>INTRODUCTION</b>Minimally invasive hepatectomy (MIH) for patients with hepatocellular carcinoma (HCC) is technically challenging, especially with large posteriorly located tumours or background of liver cirrhosis. This is a case-control study comparing the long-term oncological safety of HCC patients who underwent MIH and open hepatectomy (OH). Most of these patients have liver cirrhosis compared to other studies.</p><p><b>MATERIALS AND METHODS</b>Sixty patients were divided into 2 groups, 30 underwent MIH and 30 underwent OH for HCC resection. The patients in both groups were matched for extent of tumour resection, age and cirrhosis status. Patient characteristics, risk factors of HCC and all oncological data were studied.</p><p><b>RESULTS</b>Negative resection margins were achieved in 97% of patients in both groups. The mean blood loss during surgery was significantly lower in the MIH group compared to the OH group (361 mL vs 740 mL; 95% CI, 222.2, 734.9; P = 0.04). Hospitalisation is significantly shorter in MIH group (7 days vs 11 days; 95% CI, 6.9, 12.2,; P = 0.04). Eight patients (27%) in the MIH group and 13 patients (43%) in the OH group developed HCC recurrence (P = 0.17). One, 3 and 5 years disease-free survival between MIH and OH groups are 76% vs 55%, 58% vs 47%, and 58% vs 39% respectively (P = 0.18). One, 3 and 5 years overall survival between MIH and OH groups are 93% vs 78%, 89% vs 70%, and 59% vs 65% respectively (P = 0.41).</p><p><b>CONCLUSION</b>MIH is a safe and feasible curative treatment option for HCC with similar oncological outcomes compared to OH. MIH can be safely performed to remove tumours larger than 5 cm, in cirrhotic liver, as well as centrally and posterior located tumours. In addition, MIH patients have significant shorter hospitalisation and intraoperative blood loss.</p>

Unilateral ureteric stone associated with gross hydronephrosis and kidney shrinkage: a cadaveric report / 대한해부학회지

Ureteric stones are a common cause of obstruction of the urinary tract, usually presenting with characteristic signs and symptoms, such as acute ureteric colic and hematuria. Occasionally, stones may present with non-specific symptoms such as low back pain and remain unidentified, leading to stone growth, chronic ureteric obstruction and complications such as hydronephrosis and renal damage. Here, we report a large ureteric stone in a cadaver with complete obstruction at the left ureterovesical junction, resulting in severe dilatation of the left ureter and renal pelvis.

PAX2-null secretory cell outgrowths in the oviduct and their relationship to pelvic serous cancer.

With the exception of germ-line mutations in ovarian cancer susceptibility genes, genetic predictors for women destined for ovarian serous cancer cannot be identified in advance of malignancy. We recently showed that benign secretory cell outgrowths (SCOUTs) in the oviduct are increased in frequency with concurrent serous cancer and typically lack PAX2 expression (PAX2-null). The present study examined the relationship of PAX2-null SCOUTs to high-grade serous cancers by comparing oviducts from women with benign gynecologic conditions and high-grade serous cancers. PAX2-null SCOUTs were identified by immunostaining and computed as a function of location, frequency (F) per number of cross-sections examined, and age. Six hundred thirty-nine cross-sections from 35 serous cancers (364) and 35 controls (275) were examined. PAX2-null SCOUTs consisted of discrete linear stretches of altered epithelium ranging from cuboidal/columnar, to pseudostratified, the latter including ciliated differentiation. They were evenly distributed among proximal and fimbrial tubal sections. One hundred fourteen (F=0.31) and 45 (F=0.16) PAX2-null SCOUTs were identified in cases and controls, respectively. Mean individual case-specific frequencies for cases and controls were 0.39 and 0.14, respectively. SCOUT frequency increased significantly with age in both groups (P=0.01). However, when adjusted for age and the number of sections examined, the differences in frequency between cases and controls remained significant at P=0.006. This study supports a relationship between discrete PAX2 gene dysregulation in the oviduct and both increasing age and, more significantly, the presence of co-existing serous cancer. We propose a unique co-variable in benign oviductal epithelium-the PAX2-null SCOUT-that reflects underlying dysregulation in genes linked to serous neoplasia.

Distal airway stem cells yield alveoli in vitro and during lung regeneration following H1N1 influenza infection.

The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these cells assemble into discrete, Krt5+ pods and initiate expression of markers typical of alveoli. Gene expression profiles of these pods suggest that they are intermediates in the reconstitution of the alveolar-capillary network eradicated by viral infection. The dynamics of this p63-expressing stem cell in lung regeneration mirrors our parallel finding that defined pedigrees of human distal airway stem cells assemble alveoli-like structures in vitro and suggests new therapeutic avenues to acute and chronic airway disease.

Residual embryonic cells as precursors of a Barrett's-like metaplasia.

Barrett's esophagus is an intestine-like metaplasia and precursor of esophageal adenocarcinoma. Triggered by gastroesophageal reflux disease, the origin of this metaplasia remains unknown. p63-deficient mice, which lack squamous epithelia, may model acid-reflux damage. We show here that p63 null embryos rapidly develop intestine-like metaplasia with gene expression profiles similar to Barrett's metaplasia. We track its source to a unique embryonic epithelium that is normally undermined and replaced by p63-expressing cells. Significantly, we show that a discrete population of these embryonic cells persists in adult mice and humans at the squamocolumnar junction, the source of Barrett's metaplasia. We show that upon programmed damage to the squamous epithelium, these embryonic cells migrate toward adjacent, specialized squamous cells in a process that may recapitulate early Barrett's. Our findings suggest that certain precancerous lesions, such as Barrett's, initiate not from genetic alterations but from competitive interactions between cell lineages driven by opportunity.

Adhesion activity of fetal gonadal cells to EGF and discoidin domains of milk fat globule-EGF factor 8 (MFG-E8), a secreted integrin-binding protein which is transiently expressed in mouse early gonadogenesis.

MFG-E8, a secreted integrin-binding protein, consists of two EGF domains containing a RGD motif and two discoidin domains. In mouse embryogenesis, MFG-E8 is highly expressed in gonadal stromal cells near mesonephros at 11.5-12.5 dpc, but its function in gonadogenesis has not been characterized. To clarify a possible role of MFG-E8 in developing gonads, we analyzed the adhesion activity of 10.5-15.5 dpc gonadal cells to recombinant proteins of EGF or discoidin domains of MFG-E8. In EGF-coated wells, the gonadal cells at 11.5-12.5 dpc revealed a significantly higher adhesion activity as compared to those at 10.5 and 15.5 dpc, while discoidin domains showed a constant number of the adhered cells throughout these stages. To identify the adhesive cells of 11.5-dpc gonads, immunohistochemistry with anti-SF1/Ad4Bp antibody (a specific marker for supporting, steroidogenic, and coelomic epithelial cells) and staining for alkaline phosphatase (a germ cell marker) were carried out. As a result, EGF domains, as well as discoidin domains, were capable of binding to all three groups of SF1/Ad4Bp-positive and negative somatic cells, and germ cells of 11.5-dpc gonads. These findings therefore suggest that MFG-E8 mediates the cell-to-cell interaction among several somatic cell types and germ cells in mouse early gonadogenesis.

An ultrastructural study on cytotoxic effects of mono(2-ethylhexyl) phthalate (MEHP) on testes in Shiba goat in vitro

In this study, the effects of mono(2-ethylhexyl) phthalate (MEHP), one of metabolites of di(2-ethylhexyl) phthalate, on immature Shiba goat testes in vitro were examined. The testes of 2-month-old Shiba goats were cut into smaller pieces, and seeded in medium. At 1, 3, 6 and 9 hr after administration of MEHP at various concentrations (0, 100 nmol ml-1, 1 nmol ml-1, and 1 x 10-3 nmol ml-1, respectively), the specimens were obtained for light and transmission electron microscopic observations. As a result, at 1 hr after exposure to MEHP, the vacuolization and nuclear membrane rupture appeared in Sertoli cells. Such alterations tended to gradually increase in number in timeand dose-dependent manners. Moreover, by MEHP treatment, apoptotic spermatogenic cells (characterized with chromatin condensation, cytoplasm shrinkage without membrane rupture, still functioning cell organelles, and packed cell contents in membrane-bounded bodies), apoptotic Sertoli cells (characterized with nuclear membrane lysis, nuclear condensation), necrotic spermatogenic cells (characterized with swollen and ruptured mitochondria, plasma membrane lysis, spilt cell contents, and chromatin clumps), and necrotic Sertoli cells (characterized with marginated chromatins along the nuclear membrane, ruptured vesicles within the MNB, some swollen and ruptured cell organelles, e.g. mitochondria) could be identified. Conclusively, ultrastructurally the treatment with MEHP at low concentration tends to lead spermatogenic and Sertoli cells to apoptosis, whereas that at high concentration tends to lead spermatogenic and Sertoli cells to necrosis. Thus, the testicular tissue culture is advantageous for screening testicular toxicity of chemicals.