No abstract

Systemic lupus erythematosus (SLE) is a chronic, life threatening autoimmune disorder, leading to multiple organ pathologies and kidney destruction. Analyses of numerous murine models of spontaneous SLE have revealed a critical role for endosomal Toll-like receptors (TLRs) in the production of autoantibodies and development of other clinical disease manifestations. Nevertheless, the corresponding TLR9-deficient autoimmune-prone strains consistently develop more severe disease pathology. Injection of BALB/c mice with 2,6,10,14-tetramethylpentadecane (TMPD), commonly known as pristane, also results in the development of SLE-like disease. We now show that Tlr9−/− BALB/c mice injected intraperitoneally with TMPD develop more severe autoimmunity than their TLR-sufficient cohorts. Early indications include an increased accumulation of TLR7-expressing Ly6Chi inflammatory monocytes at the site of injection, upregulation of interferon regulated gene expression in the peritoneal cavity, and an increased production of myeloid lineage precursors (CMP and GMP) in the bone marrow. TMPD-injected Tlr9−/− BALB/c mice develop higher autoantibody titers against RNA, neutrophil cytoplasmic antigens (ANCA), and myeloperoxidase (MPO) than TMPD-injected WT BALB/c mice. The TMP-injected Tlr9−/− mice, and not the WT mice, also develop a marked increase in glomerular IgG deposition and infiltrating granulocytes, much more severe glomerulonephritis, and a reduced lifespan. Together the data point to a major role for TLR7 in the response to self-antigens in this model of experimental autoimmunity. Therefore the BALB/c pristane model recapitulates other TLR7-driven spontaneous models of SLE and is negatively regulated by TLR9.

Protein arginine deiminase (PAD) enzymes catalyze the conversion of protein-bound arginine into citrulline, an irreversible posttranslational modification with loss of a positive charge that can influence protein–protein interactions and protein structure. Protein arginine deiminase activity depends on high intracellular calcium concentrations occurring in dying cells. In this study, we demonstrate that protein citrullination is common during pyroptotic cell death in macrophages and that inhibition of PAD enzyme activity by Cl-amidine, a pan-PAD inhibitor, blocks NLRP3 inflammasome assembly and proinflammatory IL-1β release in macrophages. Genetic deficiency of either PAD2 or PAD4 alone in murine macrophages does not impair IL-1β release; however, pharmacological inhibition or small interfering RNA knockdown of PAD2 within PAD4−/− macrophages does. Our results suggest that PAD2 and 4 activity in macrophages is required for optimal inflammasome assembly and IL-1β release, a finding of importance for autoimmune diseases and inflammation.

Our findings suggest that pyroptotic CD14⁺⁺CD16⁻ classical monocytes of HIV-1-infected patients release ASC specks into the blood stream, a phenomenon that may contribute to HIV-1 induced inflammation and immune activation.

Vulvar lichen sclerosus (VLS) is a chronic inflammatory disorder, which affects women of all ages. The aim of this review is to focus on first-line, second-line, and maintenance therapies as well as follow-up of women with VLS. With numerous controversies, we decided to conduct a scoping review on this subject. A review protocol was developed, and the Knowledge Resource Services website was used to run a search of articles pertaining to VLS with keywords "Vulvar," "Vulval," and "Lichen Sclerosus." The search was limited to published data from the last 10 years, i.e., July 2009 onward, and researches published in English language. A total of 338 articles pertaining to VLS were obtained. Out of this, 62 were original articles related to management of VLS. Effective treatments such as high-potency topical steroids are now the standard of care and first-line treatment. Follow-up may be done every three to six months for the first two years and then at least yearly to ensure adequacy of treatment and encourage compliance. Long-term follow-up in specialist clinics is recommended for women who have persistent complaints, thickened skin, or history of neoplastic lesion. Monitoring young patients yearly is recommended as there are chances of recurrence.

Background:Breast lumps constitute a significant proportion of surgical cases in women of both developed and developing countries. The aim of this study is to look the frequency distribution of various breast lesions on fine needle aspiration (FNA).Materials and Methods:The 902 patients who presented with palpable breast lump, irrespective of age and sex were included in the study. Frequency distribution of various breast lesions with respect to age and sex was studied. Cytology grading in breast carcinoma was correlated in 69 cases with histology grading.Results:The majority (N = 871) of patients were females with maximum (N = 566) patients between second and third decade. The 773 patients had benign breast lesions and maximum (N = 341) patients were in the second decade. Fibroadenoma was the commonest benign lesion followed by fibrocystic change and mastitis. Out of 119 malignant breast lesions, 31.93% [N = 38] were between 41-50 years of age, 28.57% [N = 34] in 51-60 years and 22.68% [N = 27] in between 31-40 years of age. Out of 119 malignant breast lumps and majority were infiltrating ductal carcinoma (N = 108). Cytology grading correlated maximum with histology grade in Grade I followed by Grade II and Grade III.Conclusion:With experienced hands, FNA is safe, cost effective and a reliable technique for preoperative evaluation of palpable breast lumps. FNA features are more informative when combined with physical and radiology findings (Triple test). Fibroadenoma, fibrocystic change and mastitis form the major bulk of benign breast lesions. Epithelioid cells when seen in inflammatory breast FNA smears, tuberculosis must be ruled out. In India, breast carcinoma arises in younger patients as compared to western countries. Grading of breast carcinomas must be done on FNA smears for selecting neoadjuvent therapy. Clinical breast examination and mammography screening in females should be encouraged in developing countries from the third decade onwards for early detection of breast carcinoma.

Introduction:With introduction of the term “ossteointegration of dental implant” by Branemark, advancement in implantology from 1957 to 2017 has come a long way with modification in implant type and in loading time. This study aims to evaluate the survival of endo-osseous immediate loading (IL) implant and basal IL implants in atrophic jaws with objective to compare implant survival in atrophic jaws for full mouth rehabilitation between endo-osseous IL versus endo-osseous delayed loading (DL) versus basal IL during 3-year follow-up.Materials and Methods:Fifty-two (34 endo-osseous and 18 basal) implants were placed in 4 patients requiring full mouth rehabilitation in atrophic jaws. Case 1: Endo-osseous DL implants in upper and lower arch, Case 2: Endo-osseous IL implants in upper and lower arch, Case 3: Basal IL implant in upper and lower arch, and Case 4: Endo-osseous DL in upper arch and basal IL implant in the lower arch. Intraoperative evaluation was done on the basis of pain (visual analog scale [VAS]), operative time, and initial primary implant stability. Postoperative evaluation was done on pain (VAS), infection, radiographically successful implant (orthopantomogram), and patient satisfaction (Grade 0–10).Results:All cases showed satisfactory results but more amount of intra- and post-operative pain was felt with immediate basal implants.Conclusion:We believe that clinicians should comply with patient requests, and for this reason, we agree with some authors to use minimally invasive techniques and to avoid when possible esthetic or functional problems associated with the use of removable prosthesis after teeth extractions.

HIV-1 infection results in immunological abnormalities of natural killer (NK) cells such as disturbed distribution of NK cell subsets and downmodulation of activating and upregulation of inhibitory receptors thereby diminishing NK cell killing capacity and cytokine secretion. Antiretroviral treatment (ART) is known to restore phenotype and functions of NK cells. However, the effects of ART on NK cell terminal differentiation, activation, and disturbed distribution have not been studied yet longitudinally. Here, we analyzed the effects of ART on these parameters of peripheral blood NK cells in a longitudinal as well as in a cross-sectional study. We observed that expanded CD56(-)CD16(+) NK cell frequency is inversely correlated with the frequency of CD56(dim)CD16(+) NK cells in treatment-naive HIV-1 patients. Loss of CD56(dim)CD16(+) and expansion of CD56(-)CD16(+) NK cells again restore to the levels of healthy controls after ART. Enhanced immune activation of different NK cell subsets is partially restored after ART. Terminal differentiation of CD56(dim)CD16(+) NK cells is enhanced after ART as measured by CD57 expression. Frequencies of CD57(+)CD56(dim)CD16(+) NK cells are directly correlated with the frequencies of total NK cells suggesting that an increase in the frequencies of CD57(+)CD56(dim)CD16(+) NK cells is reflected by increased frequencies of total NK cells after ART. Taken together these data demonstrate that ART has an effect on the immune restoration of NK cells and is enhanced in the terminal differentiation of CD56(dim)CD16(+) NK cells, which is associated with increased frequencies of total NK cells after ART.