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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Adenosine deaminase estimation and multiplex polymerase chain reaction in diagnosis of extra-pulmonary tuberculosis.

SETTING: Extra-pulmonary tuberculosis (EPTB), including mycobacteriosis, contributes 15-20% of all tuberculosis (TB) cases. The diagnosis of EPTB remains elusive because of the inadequate sensitivity of routine and conventional bacteriological methods for the detection of Mycobacterium tuberculosis and related organisms in clinical specimens such as cerebrospinal fluid (CSF), pleural fluid and peritoneal fluid. OBJECTIVE: To develop a better diagnostic marker for EPTB. DESIGN: In our study, 179 cases of EPTB were analysed for acid-fast bacilli (AFB) smear, adenosine deaminase activity (ADA) and multiplex polymerase chain reaction (PCR). Although estimation of ADA is helpful, its sensitivity and specificity varies widely. On the other hand, a multiplex PCR using amplicons such as IS6110, dnaJ gene and hsp65 genes has high sensitivity (60-88%) and specificity (81-100%). RESULTS: On comparing AFB and ADA results with PCR, the PCR is clearly more effective than AFB (P < 0.001) and ADA estimation (P < 0.02) in CSF. The same result was observed with peritoneal fluid (P < 0.001 vs. P < 0.05) and pleural fluid (P < 0.001 and P < 0.05). CONCLUSION: The study shows that multiplex PCR remains the best tool and is a much better marker for diagnosing EPTB.

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.

Massive recurrent hemorrhage due to duodenal diverticulum--role of tattooing and suture plication.

We report a 79-year-old lady with massive recurrent GI bleeding from a duodenal diverticulum arising at the mesenteric border. We used tattooing during endoscopy as a method for identifying the bleeding source at surgery. The diverticulum was treated with suture plication.

Scleredema of Buschke: a rare post-streptococcal complication.

A 19-year male presented with acute onset, gradually progressive symmetric indurations involving the skin over the face, neck, shoulders and upper part of chest following an upper respiratory tract infection. Detailed history and examination did not reveal evidence of Raynauds' phenomenon, nail changes, digital ulcers, pigmentation or any systemic involvement. Autoantibodies for systemic sclerosis were absent. Histopathology of skin biopsy documented scleredema. Antistreptolysin O (ASO) titer was elevated. We diagnosed a case of Scleredema adultorum of Buschke following a streptococcal throat infection. We report this case to highlight the importance of clinically differentiating this relatively benign, self-limiting disorder from systemic sclerosis.

Cytoplasmic localization of the oncogenic protein Ski in human cutaneous melanomas in vivo: functional implications for transforming growth factor beta signaling.

The oncogenic protein Ski associates with Smad proteins and counteracts their activation of gene expression and growth inhibition in response to transforming growth factor beta (TGF-beta). Here we show that Ski protein levels are increased in all 44 human melanoma tumor tissues analyzed in vivo. In addition, Ski subcellular localization changes from nuclear, in preinvasive melanomas (melanomas in situ), to nuclear and cytoplasmic in primary invasive and metastatic melanomas. Furthermore, Ski/Smad association in the cytoplasm seems to prevent Smad3 nuclear translocation in response to TGF-beta. The biological significance of Ski overexpression in melanomas was established by showing that down-regulation of Ski levels, by antisense Ski vectors, restored TGF-beta-mediated growth inhibition. Such inhibition is apparently mediated by up-regulation of the cyclin-dependent kinase-I p21(Waf-1) and inhibition of cyclin-dependent kinase 2 activity. Our results suggest that high levels of Ski in human melanomas produce a disruption of TGF-beta signaling phenotypically similar to that in cells harboring mutations in TGF-beta receptors or Smad proteins, and this may represent a significant event in the progression of melanomas in vivo.

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.