Interferon regulatory factor 6 ( IRF6) acts as a tumor suppressor and controls cell differentiation in ectodermal and craniofacial tissues by regulating expression of target genes. Haploinsufficiency of IRF6 causes Van der Woude and popliteal pterygium syndrome, 2 syndromic forms of cleft lip and palate. Around 85% of patients with Van der Woude express pits on the lower lip that continuously or intermittently drain saliva, and patients with the common cleft lip and palate have a higher prevalence of dental caries and gingivitis. This study aims to identify the role of IRF6 in development of exocrine glands, specifically the major salivary glands. Our transgenic mouse model that expresses LacZ reporter under the control of the human IRF6 enhancer element showed high expression of IRF6 in major and minor salivary glands and ducts. Immunostaining data also confirmed the endogenous expression of IRF6 in the developing ductal, serous, and mucous acinar cells of salivary glands. As such, we hypothesized that Irf6 is important for proper development of salivary glands and potentially other exocrine glands. Loss of Irf6 in mice causes an increase in the proliferation level of salivary cells, disorganized branching morphogenesis, and a lack of differentiated mucous acinar cells in submandibular and sublingual glands. Expression and localization of the acinar differentiation marker MIST1 were altered in Irf6-null salivary gland and pancreas. The RNA-Seq analysis demonstrated that 168 genes are differentially expressed and confer functions associated with transmembrane transporter activity, spliceosome, and transcriptional regulation. Furthermore, expression of genes involved in the EGF pathway-that is, Ereg, Ltbp4, Matn1, Matn3, and Tpo-was decreased at embryonic day 14.5, while levels of apoptotic proteins were elevated at postnatal day 0. In conclusion, our data report a novel role of Irf6 in exocrine gland development and support a rationale for performing exocrine functional tests for patients with IRF6-damaging mutations.

Background: Chronic venous insufficiency (CVI) is an underestimated public health problem involving the lower limbs. It exerts a significant impact on patient's quality of life (QoL). The severity of the disease was measured by venous clinical severity score (VCSS) and venous disability score (VDS). Aims: The aim of the study was to evaluate VCSS, VDS, and dermatology life quality index (DLQI) among the patients of CVI and to evaluate the correlation among DLQI with VCSS, VDS, and leg ulcer. Materials and Methods: In this institution-based cross-sectional study, clinically and sonographically confirmed cases of CVI were included. Clinical severity of the disease and disability were assessed by using VCSS and VDS, respectively. QoL was assessed by a validated DLQI questionnaire. Correlation between DLQI with VCSS and VDS was analyzed. The association between DLQI with different characteristics of the ulcer was also evaluated. Results: Mean VCSS, VDS, and DLQI in the study population were 11 ± 4.96, 1.47 ± 0.67, and 6.94 ± 3.87, respectively. Both VCSS and VDS had a strong positive correlation with DLQI. The number of active ulcers, size of the ulcer, and duration of the ulcer had a strong positive correlation, whereas the age of onset of the disease had a negative correlation and duration of the disease had poor correlation with DLQI. Pain ( P = 0.03) and edema ( P = 0.04) had significant association with VDS. Conclusion: VCSS and VDS are important tools for measuring severity and disability in CVI, respectively. CVI had a strong impact on patients QoL more than it was thought hitherto.

Background: Systemic sclerosis (SSc) is an autoimmune connective tissue disorder causing microvascular abnormality leading to Raynaud's phenomenon, skin tightening, and nailfold capillary changes. The patient may have systemic involvement, among them interstitial lung disease (ILD) and pulmonary arterial hypertension are mainly associated with disease-related mortality. Aims: To find out an association between nailfold capillaroscopic changes with ILD severity. Materials and Methods: An institution based cross-sectional study was performed among the patients of SSc above 18 years. Detailed history was taken. Clinical examinations, nailfold capillaroscopy (NFC) with a dermatoscope and high-resolution computed tomography (HRCT) scan of thorax were done. Data were analyzed in MedCalc statistical software version 20. Results: Out of total 43 patients, 74.4% ( n = 32) were female. Mean age was 35.05 ± 7.24 years and mean duration 4.28 ± 2.81 years. Diffuse SSc was found in 88.37% ( n = 38). On NFC, early, active, and late patterns were found in 30.2% ( n = 13), 25.6% ( n = 11), and 44.2% ( n = 19) cases, respectively. On HRCT, early, active, and late ILD were present in 18.6% ( n = 8), 37.2% ( n = 16), and 30.2% ( n = 13) cases, respectively. ILD changes were absent in 14% ( n = 6) though NFC changes were present in them. Respiratory symptoms were absent in 20.93% ( n = 9) patients though all had features of early NFC and among them 9.3% ( n = 4) showed early ILD changes on HRCT. Significant associations were found between NFC changes and ILD severity ( P = 0.0003), NFC changes and respiratory symptoms ( P < 0.0001) and between ILD changes and respiratory symptoms ( P < 0.0001). Discussion: NFC, an inexpensive procedure, can be performed in all patients of SSc to detect development of early ILD even before appearance of respiratory symptoms to prevent further progression.

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