Molecular Signatures of Senescence in Periodontitis: Clinical Insights.

Most of the elderly population is afflicted by periodontal diseases, creating a health burden worldwide. Cellular senescence is one of the hallmarks of aging and associated with several chronic comorbidities. Senescent cells produce a variety of deleterious secretions, collectively termed the senescence-associated secretory phenotype (SASP). This disrupts neighboring cells, leading to further senescence propagation and inciting chronic inflammation, known as "inflammaging." Detrimental repercussions within the tissue microenvironment can trigger senescence at a younger age, accelerate biological aging, and drive the initiation or progression of diseases. Here, we investigated the biological signatures of senescence in healthy and diseased gingival tissues by assessing the levels of key senescence markers (p16, lipofuscin, and ß-galactosidase) and inflammatory mediators (interleukin [IL]-1ß, IL-6, IL-8, matrix metalloproteinase [MMP]-1, MMP-3, and tumor necrosis factor-α). Our results showed significantly increased senescence features including p16, lipofuscin, and ß-galactosidase in both epithelial and connective tissues of periodontitis patients compared with healthy sites in all age groups, indicating that an inflammatory microenvironment can trigger senescence-like alterations in younger diseased gingival tissues as well. Subsequent analyses using double staining with specific cell markers noted the enrichment of ß-galactosidase in fibroblasts and macrophages. Concurrently, inflammatory mediators consistent with SASP were increased in the gingival biopsies obtained from periodontitis lesions. Together, our findings provide the first clinical report revealing susceptibility to elevated senescence and inflammatory milieu consistent with senescence secretome in gingival tissues, thus introducing senescence as one of the drivers of pathological events in the oral mucosa and a novel strategy for targeted interventions.

Linear lesions in dermatology: a clinicoaetiopathological study.

BACKGROUND: Linear lesions are fairly common in our daily practice. However, the appearance of these lesions can vary, thus complicating the diagnosis. AIMS: To study the various clinical presentations, the demographic profile of patients and the clinicopathological correlations of dermatoses presenting with a linear distribution. METHODS: We conducted an institution-based, cross-sectional, descriptive study of 281 consecutive patients with linear lesions attending dermatology clinics. MedCalc software (V11.6) was used for statistical analysis. RESULTS: Patients were divided into eight groups: lesions along the lines of Blaschko (n = 136), lesions along blood vessels (n = 3), lesions along lymphatics (n = 3), Koebner phenomenon (n = 24), autoinoculation (n = 24), external factors (n = 45), infestations (n = 2) and 'other' (n = 44). The mean age at presentation was 24.50 ± 18.82 years and the male/female ratio was 1.32 : 1. The commonest symptom was itching/burning (56.94% of patients), while the commonest site was the arm (44.48%); followed by the leg (30.60%), trunk and abdomen (22.42%), head and neck (19.20%), and genitalia (0.35%). Apart from the common cases, there was a wide gamut of rare conditions (e.g. angiokeratoma circumscriptum naeviforme, porokeratotic eccrine ostial and dermal duct naevus, Blaschko-linear syringocystadenoma papilliferum, progressive cribriform and zosteriform hyperpigmentation, unilateral naevoid acanthosis nigricans, fixed drug eruption, discoid lupus erythematosus). CONCLUSION: Linear lesions act as diagnostic clues to many dermatological conditions, therefore, the importance of meticulous examination in clinical dermatology cannot be overemphasized.

Impacts of Zn and Cu enrichment under ocean acidification scenario on a phytoplankton community from tropical upwelling system.

Increasing dissolution of CO2 in the surface ocean is rapidly decreasing its pH and changing carbon chemistry which is further affecting marine biota in several ways. Phytoplankton response studies under the combination of elevated CO2 and trace metals are rare. We have conducted two consecutive onboard incubation experiments (R. V. Sindhu Sadhana; August 2017) in the eastern Arabian Sea (SW coast of India) during an upwelling event. A nutrient enriched diatom bloom was initiated onboard and grown under ambient (≈400 µatm, A-CO2) and high CO2 levels (≈1000 µatm; H-CO2) with different zinc (Zn; 1 nM) and copper (Cu) concentrations (1 nM, 2 nM and 8 nM). Phytoplankton community composition and the dominant genera were different during these two experiments. CO2 enrichment alone did not show any significant growth stimulating impact on the experimental community except enhanced cell density in the first experiment. Addition of Zn at A-CO2 level revealed no noticeable responses; whereas, the same treatment under H-CO2 level significantly reduced cell number. Considerably high protein content under H-CO2+Zn treatment was possibly counteracting Zn toxicity which also caused slower growth rate. Cu addition did not show any noticeable impact on growth and biomass production except increased protein content as well as decreased carbohydrate: protein ratio. This can be attributed to relatively higher protein synthesis than carbohydrate to alleviate oxidative stress generated by Cu. The centric diatom Chaetoceros and toxin producing pennate diatom Pseudo-nitzschia showed no significant response to either CO2 or Zn enrichment. Large centric diatom Leptocylindrus and Skeletonema responded positively to Zn addition in both CO2 levels. The former species showed the most sensitive response at the highest Cu and H-CO2 treatment; whereas, the pennate diatoms Nitzschia and Pseudo-nitzschia (toxigenic diatom) showed higher resilience under elevated CO2 and Cu levels. This observation indicated that in future ocean, increasing CO2 concentrations and trace metal pollution may potentially alter phytoplankton community structure and may facilitate toxigenic diatom bloom in the coastal waters.

Multiple Shape Coexistence in

From detailed spectroscopy of ^{110}Cd and ^{112}Cd following the ß^{+}/electron-capture decay of ^{110,112}In and the ß^{-} decay of ^{112}Ag, very weak decay branches from nonyrast states are observed. The transition rates determined from the measured branching ratios and level lifetimes obtained with the Doppler-shift attenuation method following inelastic neutron scattering reveal collective enhancements that are suggestive of a series of rotational bands. In ^{110}Cd, a γ band built on the shape-coexisting intruder configuration is suggested. For ^{112}Cd, the 2^{+} and 3^{+} intruder γ-band members are suggested, the 0_{3}^{+} band is extended to spin 4^{+}, and the 0_{4}^{+} band is identified. The results are interpreted using beyond-mean-field calculations employing the symmetry conserving configuration mixing method with the Gogny D1S energy density functional and with the suggestion that the Cd isotopes exhibit multiple shape coexistence.

Bayesian inference in time-varying additive hazards models with applications to disease mapping.

Environmental health and disease mapping studies are often concerned with the evaluation of the combined effect of various socio-demographic and behavioral factors, and environmental exposures on time-to-events of interest, such as death of individuals, organisms or plants. In such studies, estimation of the hazard function is often of interest. In addition to known explanatory variables, the hazard function maybe subject to spatial/geographical variations, such that proximally located regions may experience similar hazards than regions that are distantly located. A popular approach for handling this type of spatially-correlated time-to-event data is the Cox's Proportional Hazards (PH) regression model with spatial frailties. However, the PH assumption poses a major practical challenge, as it entails that the effects of the various explanatory variables remain constant over time. This assumption is often unrealistic, for instance, in studies with long follow-ups where the effects of some exposures on the hazard may vary drastically over time. Our goal in this paper is to offer a flexible semiparametric additive hazards model (AH) with spatial frailties. Our proposed model allows both the frailties as well as the regression coefficients to be time-varying, thus relaxing the proportionality assumption. Our estimation framework is Bayesian, powered by carefully tailored posterior sampling strategies via Markov chain Monte Carlo techniques. We apply the model to a dataset on prostate cancer survival from the US state of Louisiana to illustrate its advantages.

Unexpected Neoplasms in Lungs Explanted From Lung Transplant Recipients: A Single-Center Experience and Review of Literature.

INTRODUCTION: Lung transplantation is a common treatment for various indications, but undiagnosed neoplasms are found in 0.5% to 2.4% of explanted lungs. We report the largest single-institution series of patients with unexpected neoplasms in explanted lungs and compare rates of undiagnosed malignancies before and after the 2005 Lung Allocation Score (LAS) update. METHODS: We reviewed the medical records of patients who underwent lung transplantation at the Cleveland Clinic from 1990 to 2014. In cases of neoplasm discovered on explant, tumor type, pathological stage, recurrence, and date of death were recorded. RESULTS: From January 1, 1990 to June 30, 2014, 1303 patients underwent lung transplantation at the Cleveland Clinic. The overall mean smoking history was 35 pack-years, and 25 undiagnosed lung malignancies were found upon explant in 24 transplant recipients (1.84%). In the post-LAS era (ie, 2005 onward), 20/812 lung transplant recipients had 21 incidental neoplasms in their explanted lungs (2.5%). Seventeen of these 25 tumors occurred in patients with interstitial lung disease; 8 occurred in patients with centrilobular emphysema. Eight tumors recurred (6 in patients with interstitial lung disease and 2 in patients with emphysema). The most common histological tumor types were adenocarcinomas (n = 14) and squamous cell carcinomas (n = 7). CONCLUSIONS: Unexpected neoplasms were found in 1.84% of lung transplant recipients' explanted lungs, with a slightly higher incidence (2.46%) in the post-LAS era. Neoplasms were more common in patients with interstitial lung diseases than in patients with centrilobular emphysema. Explanted lungs should be pathologically examined for evidence of tumor foci because this can impact post-transplantation management.

An interesting case of renal amyloidosis.

In amyloidosis, there is an extracellular deposition of beta-sheet fibrils. Over 25 proteins have been demonstrated to form amyloid. One of them is Ig amyloid light (AL) chains. We are presenting a 40-year-old female who presented with progressive kyphoscoliosis for last 2 years following a minor trauma and bilateral pedal edema for last 3 months. On further investigation, we found that she had a biclonal variety of MM with amyloidosis of kidney leading to massive proteinuria. Very few case reports are available where patient with biclonal variety of MM develop renal amyloidosis.

Plasmablastic lymphoma in HIV patients: Experience at a tertiary care hospital in eastern India.

BACKGROUND: Plasmablastic lymphoma (PBL), a rare non-Hodgkin's lymphoma (NHL) variant specifically associated with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), expresses well-differentiated plasma cell markers like CD138, bright CD38, and MUM1; but not conventional B-cell markers. It occurs at unusual sites like oral cavity and orbit, and has poor survival rates. AIMS: This study serves as a review of a clinical experience with six HIV patients with PBL and observes the spectrum of clinical presentations, histopathologies, and 1-year outcomes in PBL patients. MATERIALS AND METHODS: This review of six PBL patients was conducted at a tertiary care hospital in eastern India using relevant radiological, histopathogical, and immunohistological studies. RESULTS: Incidence of PBL among HIV patients was 0.58% (6/1,028). Mean CD4 count at presentation was 125.5 ± 71.1 cells/µL. Sites of involvement included pleura, lung parenchyma, suprarenal gland, pelvic cavity, and retroorbital space (one each). Immunohistopathology of biopsied sample in each patient revealed PBL (positive plasma cell markers MUM-1/IRF4, CD38, and CD138/syndecan; and negative of B-cell markers CD3, CD20, and CD30). Three (60%) were positive for Epstein Barr virus (EBV) immunoglobulin G (IgG). Five surviving patients received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen and attained partial remission (PR) after six cycles. Subsequently, three patients were started on EPOCH (etoposide, cyclophosphamide, doxorubicin, vincristine, prednisone) therapy; two attained near total regression after 6 months (four cycles). Overall, four patients remained alive with good quality of life at the end of 1 year of follow-up. CONCLUSION: PBL in HIV occurs at unusual sites with varying aggressivity. This study is too small to comment on the long-term outcomes of PBL in HIV; however, coadministration of antiretroviral therapy (ART) with standard chemotherapy may improve survival.

Possible role of Toll-like receptor-2 in the intracellular survival of Staphylococcus aureus in murine peritoneal macrophages: involvement of cytokines and anti-oxidant enzymes.

Effects of blocking toll-like receptor-2 (TLR-2) on the survival of Staphylococcus aureus (S. aureus) and cytokine production in peritoneal macrophages of Swiss albino mice were analysed. Macrophages were infected with S. aureus in the presence and absence of anti-TLR-2 antibody. Tumour necrosis factor-α (TNF-α) interleukin-6 (IL-6), interferon-gamma (IFN-γ), interleukin-1ß (IL-1ß), interleukin-12 (IL-12) and interleukin-10 (IL-10) concentrations were measured. Expressions of TLR-2, NF-κB, MyD 88 were analysed by Western Blot. Expression of TLR-2 was increased in S. aureus-infected macrophages with respect to control and was MyD 88 independent. TLR2 blocking significantly reduced TNF-α, IL-6, IL-1ß and IL-10 and increased IFN-γ and IL-12 production. Decreased catalase activity and increased superoxide dismutase (SOD) by S. aureus with concomitant increase in H2 O2 and nitric oxide (NO) were observed in the case of prior TLR-2 blocking. To understand whether catalase contributing in the intracellular survival, was of bacterial origin or not, 3-amino, 1, 2, 4-triazole (ATZ) was used to inhibit specifically macrophage-derived catalase. Catalase enzyme activity from the whole staphylococcal cells in the presence of ATZ suggested that the released catalase were of extracellular origin. From the intracellular survival assay, it was evident that pretreatment of macrophages with ATZ reduces the bacterial burden in macrophages when infected with the recovered bacteria only from the anti-TLR-2 antibody-treated macrophages after phagocytosis. Catalase protein expression from the whole staphylococcal cells recovered after phagocytosis also indicated the catalase release from S. aureus. Capturing of S. aureus via TLR-2 induces inflammatory reactions through activation of NF-κB-signalling pathways which was MyD88-independent.

Gentamicin in combination with ascorbic acid regulates the severity of Staphylococcus aureus infection-induced septic arthritis in mice.

To study the effects of gentamicin in combination with ascorbic acid on septic arthritis, mice were infected with Staphylococcus aureus (S. aureus) and treated with gentamicin, which was given at 5 mg/kg after 24 h of infection, followed by ascorbic acid, given at 20 mg/kg body weight after 2 h of gentamicin treatment. Mice were sacrificed at 3, 9, 15 days post-infection (dpi). Combined treatment of infected mice with gentamicin and ascorbic acid eradicated the bacteria from the blood, spleen and synovial tissue and showed a significant gross reduction in arthritis, reduced serum levels of tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). S. aureus-infected mice have demonstrated the disturbed antioxidant status measured in terms of cellular antioxidants like reduced glutathione and antioxidant enzymes such as superoxide dismutase (SOD) and catalase. The same were ameliorated when the animals were co-treated with gentamicin along with ascorbic acid.

Fall frequency and risk assessment in early Parkinson's disease.

BACKGROUND: We sought to define the frequency of falls in early PD and assess potential risk factors for falls in this population. METHODS: We analyzed the data from two randomized, placebo controlled trials (NET-PD FS1 and FS-TOO) of 413 individuals with early PD over 18 months of follow-up in FS1 and 12 months in FS-TOO. Falls were defined as any report of falls on the UPDRS or the adverse event log. We assessed the frequency of falls overall and by age. The relationship between prespecified fall risk markers and the probability of falling was assessed using logistic and multiple logistic regression. A hurdle Poisson model was used to jointly model the probability of remaining fall-free and the number of falls. RESULTS: During the follow-up period, 23% of participants fell, and 11% were habitual fallers. In a multiple logistic regression model, age, baseline UPDRS Falling score, and baseline PDQ-39 scores were associated with subsequent fall risk (p < 0.001). Similarly, in a hurdle Poisson regression model, age, baseline UPDRS falling item, and baseline PDQ-39 were all significantly related to the probability of falling, but only UPDRS falling >0 was associated with the number of falls. CONCLUSION: Falls are frequent and are associated with impaired quality of life, even in early PD. Current standard rating scales do not sufficiently explain future fall risk in the absence of a prior fall history. New assessment methods for falls and postural instability are required to better evaluate this important problem in clinical trials and clinical practice.

Prognostic markers in AIDS-related cryptococcal meningitis.

OBJECTIVE: Despite the advent and expanding access to antiretroviral therapy, HIV-associated cryptococcal meningitis (CM) remains a significant cause of mortality and morbidity amongst individuals with this infection in resource-limited settings. METHODS: We prospectively studied the clinical, biochemical and mycological parameters of 30 HIV patients diagnosed with cryptococcal meningitis at our centre over a period of 6 months with a view to identify prognostic factors predictive of poor outcome. RESULTS: Our study documented a mortality rate of 36.7%. Age, sex and previous diagnosis of HIV had no bearing on the survival outcome of patients. The study identified several poor prognostic factors including low GCS score, papilledema, elevated CSF opening pressure (>250 mm of H2O) and lack of regular HIV care in those with a prior diagnosis of HIV. CSF pleocytosis was significantly higher in the mortality group. CONCLUSION: There have been relatively few attempts to focus on poor prognostic markers associated with AIDS related Cryptococcal meningitis in Asian patients. Our study highlights how simple bedside clinical tools like ophthalmoscopy and CSF manometry can help in risk stratification in this group of patients.

Effectiveness and safety of leflunomide for pulmonary and extrapulmonary sarcoidosis.

Leflunomide has been reported as an alternative therapy in sarcoidosis. However, the published data are limited. We performed a retrospective chart review of the tolerance and effects of leflunomide therapy in patients with sarcoidosis. 76 patients were included. The most common reasons for initiation were progression of disease or failure of other immunomodulator therapy. Side-effects attributable to leflunomide were noted in 34% of subjects, prompting discontinuation in 17%. The lungs were a target of therapy in 33 (44%) and extrapulmonary organs were a target in 45 (59%). The mean ± sd change in forced vital capacity in the 6 months prior to leflunomide was -0.1 ± 0.3 L, and it was +0.09 ± 0.3 L in the following 6 months (p=0.01). For extrapulmonary target organ response, 51% had a good response and 32% a partial response. The median corticosteroid dose at initiation was 10 mg (interquartile range 5-20) mg at baseline, and 0 (0-10) mg at the 6-month follow-up (p<0.001). Leflunomide is a viable alternative agent for pulmonary and extrapulmonary sarcoidosis. Leflunomide appears to facilitate reduction of steroid dose and can be considered as monotherapy or as add-on therapy in cases of progressive disease.

High-precision half-life measurement for the superallowed ß+ emitter ²6Al(m).

A high-precision half-life measurement for the superallowed ß+ emitter 26Al(m) was performed at the TRIUMF-ISAC radioactive ion beam facility yielding T 1/2 6346.54 ± 0.46(stat) ± 0.60 (syst) ms, consistent with, but 2.5 times more precise than, the previous world average. The 26Al(m) half-life and ft value, 3037.53(61) s, are now the most precisely determined for any superallowed ß decay. Combined with recent theoretical corrections for isospin-symmetry-breaking and radiative effects, the corrected Ft value for (26)Al(m), 3073.0(12) s, sets a new benchmark for the high-precision superallowed Fermi ß-decay studies used to test the conserved vector current hypothesis and determine the V(ud) element of the Cabibbo-Kobayashi-Maskawa quark mixing matrix.

Laparoscopic resection for recurrent Crohn's disease: safety, feasibility and short-term outcomes.

AIM: The safety, feasibility and short-term outcomes of laparoscopic resection were assessed in patients with recurrent ileocolic Crohn's disease. METHOD: A consecutive series of patients was identified from a prospectively collated database. Data included patient demographics, previous medical and surgical treatment, operative details and postoperative course. Data from the original index open operation were collected retrospectively by review of the case notes. RESULTS: Between 2005 and 2009, 27 patients [21 women, mean (range) age 31 years (16-51 years)] underwent laparoscopic resection for recurrent ileocolic Crohn's disease. All had histologically confirmed recurrent disease at the ileocolic anastomosis. Five (18.5%) patients required extended resection for Crohn's colitis, three (11.1%) had fistulating disease and one (3.4%) patient had a psoas abscess. The median (range) operative time was 110 min (70-170 min) with a conversion rate of two (7.4%) of 27 patients. The length of stay was 4 days (2-7 days) with time to return to work or full activity of 3.5 weeks (2-7 weeks). CONCLUSION: Laparoscopic resection of recurrent ileocolic Crohn's disease is safe, feasible and associated with short-term benefits.

Robust Bayesian Analysis of Heavy-tailed Stochastic Volatility Models using Scale Mixtures of Normal Distributions.

A Bayesian analysis of stochastic volatility (SV) models using the class of symmetric scale mixtures of normal (SMN) distributions is considered. In the face of non-normality, this provides an appealing robust alternative to the routine use of the normal distribution. Specific distributions examined include the normal, student-t, slash and the variance gamma distributions. Using a Bayesian paradigm, an efficient Markov chain Monte Carlo (MCMC) algorithm is introduced for parameter estimation. Moreover, the mixing parameters obtained as a by-product of the scale mixture representation can be used to identify outliers. The methods developed are applied to analyze daily stock returns data on S&P500 index. Bayesian model selection criteria as well as out-of- sample forecasting results reveal that the SV models based on heavy-tailed SMN distributions provide significant improvement in model fit as well as prediction to the S&P500 index data over the usual normal model.

Symmetrical peripheral gangrene: a prospective study of 14 consecutive cases in a tertiary-care hospital in eastern India.

BACKGROUND: Symmetrical peripheral gangrene (SPG) is characterized by sudden onset of peripheral, frequently symmetrical gangrene in the absence of major vascular occlusive disease. SPG is associated with a wide range of underlying medical problems and usually has disseminated intravascular coagulation (DIC) in the background. Although sporadic cases and a few retrospective case series of SPG have been reported, lack of any prospective study on the profile and outcome of these patients prompted us to undertake the present work. OBJECTIVES: To study the clinical profile, aetiological factors, and outcome of a group of patients of SPG from eastern India. PATIENTS/METHODS: Prospective, observational study of consecutive patients presented at or referred to the Dermatology Department of a tertiary-care hospital during 2001 to 2008. RESULTS: We observed 14 patients (5 males, 9 females; mean age: 43.36 years) of SPG during the study period. All had clinical and laboratory evidence of DIC in association with a shock syndrome. Associated purpura fulminans was noted in 11 patients. In 12 patients, the cause of SPG was infective, Pneumococcus being the commonest organism involved. Two patients developed DIC and SPG postoperatively. Nine patients survived and the remaining five patients died. Three patients had leukopenia and all of them died. Amongst the survivors, four patients had auto-amputation of some parts of distal limbs; surgical amputation was done in two patients. CONCLUSIONS: SPG carries a high mortality rate frequently requiring multiple limb amputations in survivors. Leukopenia may be a poor prognostic factor of SPG and DIC may occur universally.

New features of shape coexistence in ;{152}Sm.

Excited states in ;{152}Sm have been investigated with the ;{152}Sm(n,n;{'}gamma) reaction. The lowest four negative-parity band structures have been characterized in detail with respect to their absolute decay properties. Specifically, a new K;{pi} = 0;{-} band has been assigned with its 1;{-} band head at 1681 keV. This newly observed band has a remarkable similarity in its E1 transition rates for decay to the first excited K;{pi} = 0;{+} band at 684 keV to the lowest K;{pi} = 0;{-} band and its decay to the ground-state band. Based on these decay properties, as well as energy considerations, this new band is assigned as a K;{pi} = 0;{-} octupole excitation based on the K;{pi} = 0_{2};{+} state. An emerging pattern of repeating excitations built on the 0_{2};{+} level similar to those built on the ground state may indicate that ;{152}Sm is a complex example of shape coexistence rather than a critical point nucleus.