Deficiency of Fibroblast Growth Factor-Inducible 14 (Fn14) Preserves the Filtration Barrier and Ameliorates Lupus Nephritis

TNF ligand superfamily member 12, also known as TNF-related weak inducer of apoptosis (TWEAK), acts through its receptor, fibroblast growth factor-inducible 14 (Fn14), to mediate several key pathologic processes involved in tissue injury relating to lupus nephritis. To explore the potential for renal protection in lupus nephritis by targeting this pathway, we introduced the Fn14 null allele into the MRL-lpr/lpr lupus mouse strain. At 26–38 weeks of age, female Fn14-knockout MRL-lpr/lpr mice had significantly lower levels of proteinuria compared with female wild-type MRL-lpr/lpr mice. Furthermore, Fn14-knockout mice had significantly improved renal histopathology accompanied by attenuated glomerular and tubulointerstitial inflammation. There was a significant reduction in glomerular Ig deposition in Fn14-knockout mice, despite no detectable differences in either serum levels of antibodies or splenic immune cell subsets. Notably, we found that the Fn14-knockout mice displayed substantial preservation of podocytes in glomeruli and that TWEAK signaling directly damaged barrier function and increased filtration through podocyte and glomerular endothelial cell monolayers. Our results show that deficiency of the Fn14 receptor significantly improves renal disease in a spontaneous lupus nephritis model through prevention of the direct injurious effects of TWEAK on the filtration barrier and/or modulation of cytokine production by resident kidney cells. Thus, blocking the TWEAK/Fn14 axis may be a novel therapeutic intervention in immune-mediated proliferative GN.     

The Effect of Alloplastic Bone Graft and Absorbable Gelatin Sponge in Prevention of Periodontal Defects on the Distal Aspect of Mandibular Second Molars,After Surgical Removal of Impacted Mandibular Third Molar: A Comparative Prospective Study

Aim

Recent studies claim that haemostatic agents can be used as bone graft substitutes. The aim of this study was to compare the efficacy of alloplastic bone graft with absorbable gelatin sponge in prevention of periodontal defects distal to mandibular second molar after the surgical removal of impacted mandibular third molars.

Materials and methods

A prospective, randomized, single-blind split-mouth study was designed. The study consisted of 25 patients requiring surgical removal of bilateral impacted mandibular 3rd molars. The surgical sites were randomly divided into 2 groups: group I: G-graft (hydroxyapatite + collagen, study group) and group II: Abgel (absorbable gelatin sponge, control group). Patients were recalled on lst and 7th postoperative days and 3rd and 6th postoperative months. Probing depth, alveolar bone levels and soft tissue wound healing were evaluated. Paired t test was used to compare pre and post-operative alveolar bone levels and probing depth (PD). Wilcoxon signed ranks test was used to compare the wound healing.

Results

The soft tissue wound healing, PD and the distance between the cemento–enamel junction on the distal aspect of mandibular second molar (point A) and the alveolar crest on the distal aspect of the same tooth (point B) were significantly higher in group I as compared to group II.

Conclusion

This study reveals an increase in the alveolar bone level, improvement of PD and better wound healing in group I. Group II subjects required longer healing time than the normal. The authors disagree the claim that the haemostatic agents can be used as bone graft substitutes. However, long-term, multicenter, randomized controlled clinical trials are required.     

Alcoholic Liver Disease and COVID-19 Pneumonia: A Case Series

The novel coronavirus 2019 (COVID-19) was reported by the World Health Organization in December 2019, and since then it has progressed into a worldwide pandemic, causing significant morbidity and mortality. Gastrointestinal symptoms of COVID-19 and elevated liver chemistries are seen in up to 50% of infected patients. Recent reports have suggested a high mortality rate for COVID-19 in patients with pre-existing liver disease, having an associated mortality of 39.8%. Alcoholic liver disease is a significant cause of morbidity and mortality in New Mexico (USA), and we report here the clinical course and characteristics of three cases of patients with alcoholic cirrhosis who were admitted to our hospital with COVID-19.     

Recent progress in development of 2,3-diaminomaleonitrile (DAMN) based chemosensors for sensing of ionic and reactive oxygen species

2,3-Diaminomaleonitrile (DAMN) has proved to be a valuable organic π-conjugated molecule having many applications in the area of chemosensors for sensing of ionic and neutral species because of its ability to act as a building block for well-defined molecular architectures and scaffolds for preorganised arrays of functionality. In this article, we discussed the utilization of 2,3-diaminomaleonitrile (DAMN) for the design and development of chemosensor molecules and their application in the area of metal ion, anion and reactive oxygen species sensing. Along with these, we present different examples of DAMN based chemosensors for multiple ion sensing. We also discuss the ion sensing mechanism and potential uses in other related areas of research.

2,3-Diamniomaleonitrile (DAMN) is valuable π-conjugated organic scaffold molecule for designing of efficient chemosensors for sensing of ionic and Reactive Oxygen Species (ROS).     

Health-related quality of life in children with cerebral palsy and their families

Objective

To determine the health-related quality of life in children with cerebral palsy and their families.

Methods

One hundred children (3–10 years of age) receiving regular rehabilitation therapy for cerebral palsy for last 1 year at a Child Development Centrer were enrolled and the Lifestyle assessment questionnaire — cerebral palsy was administered to the parents.

Results

9% had good, 24% had mildly-affected, 37% had moderately-affected and 30% had severely-affected healthrelated quality of life. The physical independence, mobility and social integration dimensions were much more severely affected than the clinical burden, economic burden and schooling dimensions.

Conclusion

Health-related quality of child is affected in most children with cerebral palsy.     

Upregulation of the ATR‐CHEK1 pathway in oral squamous cell carcinomas

The ATR‐CHEK1 pathway is upregulated and overactivated in Ataxia Telangiectasia (AT) cells, which lack functional ATM protein. Loss of ATM in AT confers radiosensitivity, although ATR‐CHEK1 pathway overactivation compensates, leads to prolonged G₂ arrest after treatment with ionizing radiation (IR), and partially reverses the radiosensitivity. We observed similar upregulation of the ATR–CHEK1 pathway in a subset of oral squamous cell carcinoma (OSCC) cell lines with ATM loss. In the present study, we report copy number gain, amplification, or translocation of the ATR gene in 8 of 20 OSCC cell lines by FISH; whereas the CHEK1 gene showed copy number loss in 12 of 20 cell lines by FISH. Quantitative PCR showed overexpression of both ATR and CHEK1 in 7 of 11 representative OSCC cell lines. Inhibition of ATR or CHEK1 with their respective siRNAs resulted in increased sensitivity of OSCC cell lines to IR by the colony survival assay. siRNA‐mediated ATR or CHEK1 knockdown led to loss of G₂ cell cycle accumulation and an increased sub‐G₀ apoptotic cell population by flow cytometric analysis. In conclusion, the ATR‐CHEK1 pathway is upregulated in a subset of OSCC with distal 11q loss and loss of the G₁ phase cell cycle checkpoint. The upregulated ATR‐CHEK1 pathway appears to protect OSCC cells from mitotic catastrophe by enhancing the G₂ checkpoint. Knockdown of ATR and/or CHEK1 increases the sensitivity of OSCC cells to IR. These findings suggest that inhibition of the upregulated ATR–CHEK1 pathway may enhance the efficacy of ionizing radiation treatment of OSCC. © 2013 Wiley Periodicals, Inc.     

Case Report: Cutaneous Leishmaniasis in Cuban Immigrants to Texas who Traveled through the Darién Jungle,Panama

Cutaneous leishmaniasis is rarely seen in the United States. Four Cuban immigrants traveled along the same route at different times from Cuba to Ecuador, then northward, including through the Darién Jungle in Panama. These patients had chronic ulcerative non-healing skin lesions and were given a diagnosis of leishmaniasis.Leishmaniasis is a vector-borne disease caused by the protozoan parasite of the genus Leishmania and is spread by the bite of sand flies from the sub-family Phlebotominae.¹ There are various clinical manifestations of leishmaniasis, including cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis, and visceral leishmaniasis. Cutaneous leishmaniasis occurs at the site of the bite, with lesions forming weeks to months later starting with a papule, which then develops into a nodule or plaque-like lesion and progresses to a painless ulceration with an indurated border.We report four cases of CL caused by Leishmania (Viannia) panamensis in Cuban immigrants who traveled through the Darién Gap Jungle between Colombia and Panama on their journey north to the United States. This region has been shown to have high transmission rates of leishmaniasis,² and, in 2012, Panama experienced an outbreak beyond expected endemic rates.³ This case series highlights a previously underappreciated immigration route to the United States for Cubans and the need to include leishmaniasis as a differential diagnosis for non-healing skin ulcers in this patient population.During May 2012–April 2013, four persons who had recently immigrated to the United States from Cuba came to the National School of Tropical Medicine at Baylor College of Medicine''s (BCM) Tropical Medicine Clinic for non-healing skin ulcers. All four persons reported a similar route of travel from Cuba to Texas (Figure 1), although at different times. Each person began their journey by flying to Quito, Ecuador, where they then traveled by bus through Colombia, passing through the cities of Pasto and Cali to Quibdo. In Quibdo, they took a short flight to Bahia Solano, Colombia, where a boat ride then transported them to Punta Ardita near the Panama border. They then traveled by foot through the thick jungle in Darién, Panama, for 5–15 days. During this time, they slept outdoors and reported numerous insect bites. Once through the Darién area, they traveled northward until they entered the United States at the Mexican border.Open in a separate windowFigure 1.Map showing immigration route of a cluster of Cuban patients with cutaneous leishmaniasis caused by Leishmania (V.) panamensis. Note the travel by foot through the thick jungle of the Darién National Park, Panama, where they likely contracted the disease.Once in the United States, the four persons sought medical care at outside clinics for skin lesions that had developed within two months after they passed though the Darién. They were treated for presumed infection with Staphylococcus aureus. The antibiotics had no therapeutic effect, and the lesions continued to grow and develop into non-healing, painless ulcers with accompanying satellite lesions. Once in Houston, Texas, the four persons were directed to the Department of Dermatology at BCM (

Worksite Health and Wellness Programs in India

Worksite health and wellness (WH&W) are gaining popularity in targeting cardiovascular (CV) risk factors among various industries. India is a large country with a larger workforce in the unorganized sector than the organized sector. This imbalance creates numerous challenges and barriers to implementation of WH&W programs in India. Large scale surveys have identified various CV risk factors across various industries. However, there is scarcity of published studies focusing on the effects of WH&W programs in India. This paper will highlight: 1) the current trend of CV risk factors across the industrial community, 2) the existing models of delivery for WH&W in India and their barriers, and 3) a concise evidence based review of various WH&W interventions in India.