Contagious keratoconjuctivitis in goats due to Branhamella (Moraxella) ovis

Incidents of contagious kerato conjuctivitis in two flocks of goats in Chalkidiki Prefecture are described. The disease was only observed in young animals approximately two years of age. The early signs were excessive lacrimation, photophobia and blepharospasm, while the bright sunlight was revealed irritating for the affected eyes. Conjunctivitis and mucopurulent secretion was also observed at the late stage of the disease. Many animals with keratitis end up totally blind. The infection of the eyes was either lateral of bilateral. Branhamella ovis was isolated in almost pure culture, from lacrimal secretion in a large number of samples (32/35). The identification was based on the organism's morphology, cultural behaviour and biochemical reactions. The microbiological examination of the samples revealed only one kind of isolate. No other organisms that could cause similar clinical findings were isolated. Therefore, it was assumed that the etiological agent of the described cases was B.ovis. It is possible that certain environmental agents such as dust, flies or bright sunlight, that were present at that time of the year because of the prolonged summer, acted as predisposing factors. Although the disease exists in our country for years, it is the first time that the pathogen agent has been isolated and identified. A successful treatment was performed at the early stage of the disease by the topical application of antibiotics.

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Proteomics profiling of human synovial fluid suggests global increased protein interplay in early-osteoarthritis (OA) and lost in late-stage OA

10.1101/2020.09.04.279422 ◽

2020 ◽

Author(s):

Neserin Ali ◽

Aleksandra Turkiewicz ◽

Velocity Hughes ◽

Elin Folkesson ◽

Jon Tjörnstand ◽

...

Keyword(s):

Synovial Fluid ◽

Late Stage ◽

Multilevel Model ◽

Molecular Mechanisms ◽

Early Stage ◽

Meniscal Tear ◽

Knee Oa ◽

Data Independent Acquisition ◽

First Time ◽

Early Oa

AbstractThe underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins on a global level in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear) and from deceased controls without knee OA.Synovial fluid samples were analyzed using state-of-the-art mass spectrometry with data-independent acquisition. The differential expression of the proteins detected was clustered and evaluated with data mining strategies and a multilevel model. Group-specific slopes of associations were estimated between expressions of each pair of identified proteins to assess the co-expression (i.e. interplay) between the proteins in each group.More proteins were increased in early-OA vs controls than late-stage OA vs controls. For most of these proteins, the fold changes between late-stage OA vs controls and early stage OA vs controls were remarkably similar suggesting potential involvement in the OA process. Further, for the first time this study illustrated distinct patterns in protein co-expression suggesting that the global interplay between the protein machinery is increased in early-OA and lost in late-stage OA. Further efforts should probably focus on earlier stages of the disease than previously considered.

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The Total Synthesis of Rhabdastrellic Acid A

10.26434/chemrxiv.7479944 ◽

2018 ◽

Author(s):

Yaroslav Boyko ◽

Christopher Huck ◽

David Sarlah

Keyword(s):

Total Synthesis ◽

Late Stage ◽

Cross Coupling ◽

Side Chains ◽

General Strategy ◽

Modular Approach ◽

Linear Sequence ◽

Generating Sequence ◽

First Time

<div>The first total synthesis of rhabdastrellic acid A, a highly cytotoxic isomalabaricane triterpenoid, has been accomplished in a linear sequence of 14 steps from commercial geranylacetone. The prominently strained <i>trans-syn-trans</i>-perhydrobenz[<i>e</i>]indene core characteristic of the isomalabaricanes is efficiently accessed in a selective manner for the first time through a rapid, complexity-generating sequence incorporating a reductive radical polyene cyclization, an unprecedented oxidative Rautenstrauch cycloisomerization, and umpolung 𝛼-substitution of a <i>p</i>-toluenesulfonylhydrazone with in situ reductive transposition. A late-stage cross-coupling in concert with a modular approach to polyunsaturated side chains renders this a general strategy for the synthesis of numerous family members of these synthetically challenging and hitherto inaccessible marine triterpenoids.</div>

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Making the Grade during Pandemic: Early-stage and Late-stage Provisional Institutions

Sociological Perspectives ◽

10.1177/07311214211028616 ◽

2021 ◽

pp. 073112142110286

Author(s):

Alexander B. Kinney ◽

Nicholas J. Rowland

Keyword(s):

Late Stage ◽

Early Stage ◽

State University ◽

Institutional Work ◽

Traditional Grading ◽

Grading Policy ◽

Temporary Solution ◽

Rural State ◽

Empirical Implications ◽

Common Understanding

This is an article that draws on the institutional work literature about provisional institutions. To date, nearly every U.S. sector has been impacted by COVID-19. To sustain their core missions, highly institutionalized organizations such as universities have had to rethink foundational structures and policies. Using a historical ethnographic approach to investigate records from faculty senate deliberations at “Rural State University” (RSU), the authors examine the implementation of a temporary grading policy to supplement traditional, qualitative grades spring 2020 during the outbreak. The authors find that RSU implemented a temporary, supplemental grading policy as a provisional institution to momentarily supersede traditional grading as a means to—as soon as possible—return to it. This finding contrasts with the common understanding that provisional institutions operate primarily as a temporary solution to a social problem that leads to more stable and enduring, ostensibly nonprovisional institutions. The temporary grading policy, the authors argue, constitutes a “late-stage” provisional institution and, with this new lens, subsequently characterize the more commonplace understanding of provisional institutions as “early-stage.” This contribution has theoretical implications for studies of institutions and empirical implications for research on shared governance and disruption in higher education.

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Health Insurance Status as a Predictor of Mode of Colon Cancer Detection but Not Stage at Diagnosis: Implications for Early Detection

Public Health Reports ◽

10.1177/0033354921999173 ◽

2021 ◽

pp. 003335492199917

Author(s):

Lindsey A. Jones ◽

Katherine C. Brewer ◽

Leslie R. Carnahan ◽

Jennifer A. Parsons ◽

Blase N. Polite ◽

...

Keyword(s):

Colon Cancer ◽

Health Insurance ◽

Early Detection ◽

Late Stage ◽

Early Stage ◽

Insurance Status ◽

Stage At Diagnosis ◽

Health Insurance Status ◽

Percentage Point Increase ◽

Point Increase

Objective For colon cancer patients, one goal of health insurance is to improve access to screening that leads to early detection, early-stage diagnosis, and polyp removal, all of which results in easier treatment and better outcomes. We examined associations among health insurance status, mode of detection (screen detection vs symptomatic presentation), and stage at diagnosis (early vs late) in a diverse sample of patients recently diagnosed with colon cancer from the Chicago metropolitan area. Methods Data came from the Colon Cancer Patterns of Care in Chicago study of racial and socioeconomic disparities in colon cancer screening, diagnosis, and care. We collected data from the medical records of non-Hispanic Black and non-Hispanic White patients aged ≥50 and diagnosed with colon cancer from October 2010 through January 2014 (N = 348). We used logistic regression with marginal standardization to model associations between health insurance status and study outcomes. Results After adjusting for age, race, sex, and socioeconomic status, being continuously insured 5 years before diagnosis and through diagnosis was associated with a 20 (95% CI, 8-33) percentage-point increase in prevalence of screen detection. Screen detection in turn was associated with a 15 (95% CI, 3-27) percentage-point increase in early-stage diagnosis; however, nearly half (47%; n = 54) of the 114 screen-detected patients were still diagnosed at late stage (stage 3 or 4). Health insurance status was not associated with earlier stage at diagnosis. Conclusions For health insurance to effectively shift stage at diagnosis, stronger associations are needed between health insurance and screening-related detection; between screening-related detection and early stage at diagnosis; or both. Findings also highlight the need to better understand factors contributing to late-stage colon cancer diagnosis despite screen detection.

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EU FP7 research funding for an orphan drug (Orfadin®) and vaccine (Hep C) development: a success and a failure?

Journal of Pharmaceutical Policy and Practice ◽

10.1186/s40545-021-00317-8 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

L. Schmidt ◽

O. Sehic ◽

C. Wild

Keyword(s):

Hepatitis C ◽

Late Stage ◽

Research Funding ◽

Early Stage ◽

Basic Research ◽

Pharmaceutical Products ◽

Clinical Development ◽

Clinical Indication ◽

Market Authorisation ◽

Risk Capital

Abstract Background We considered the extent of the contribution of publicly funded research to the late-stage clinical development of pharmaceuticals and medicinal products, based on the European Commission (EC) FP7 research funding programme. Using two EC FP7-HEALTH case study examples—representing two types of outcomes—we then estimated wider public and charitable research funding contributions. Methods Using the publicly available database of FP7-HEALTH funded projects, we identified awards relating to late-stage clinical development according to the systematic application of inclusion and exclusion criteria, classified them according to product type and clinical indication, and calculated total EC funding amounts. We then identified two case studies representing extreme outcomes: failure to proceed with the product (hepatitis C vaccine) and successful market authorisation (Orfadin® for alkaptonuria). Total public and philanthropic research funding contributions to these products were then estimated using publicly available information on funding. Results 12.3% (120/977) of all EC FP7-HEALTH awards related to the funding of late-stage clinical research, totalling € 686,871,399. Pharmaceutical products and vaccines together accounted for 84% of these late-stage clinical development research awards and 70% of its funding. The hepatitis C vaccine received total European Community (FP7 and its predecessor, EC Framework VI) funding of €13,183,813; total public and charitable research funding for this product development was estimated at € 77,060,102. The industry sponsor does not consider further development of this product viable; this now represents public risk investment. FP7 funding for the late-stage development of Orfadin® for alkaptonuria was so important that the trials it funded formed the basis for market authorisation, but it is not clear whether the price of the treatment (over €20,000 per patient per year) adequately reflects the substantial public funding contribution. Conclusions Public and charitable research funding plays an essential role, not just in early stage basic research, but also in the late-stage clinical development of products prior to market authorisation. In addition, it provides risk capital for failed products. Within this context, we consider further discussions about a public return on investment and its reflection in pricing policies and decisions justified.

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Context-Specific Efficacy of Apalutamide Therapy in Preclinical Models of Pten-Deficient Prostate Cancer

Cancers ◽

10.3390/cancers13163975 ◽

2021 ◽

Vol 13 (16) ◽

pp. 3975

Author(s):

Marco A. De Velasco ◽

Yurie Kura ◽

Naomi Ando ◽

Noriko Sako ◽

Eri Banno ◽

...

Keyword(s):

Prostate Cancer ◽

Antitumor Activity ◽

Cancer Cells ◽

Late Stage ◽

Early Stage ◽

Castration Resistant Prostate Cancer ◽

Akt Inhibitor ◽

Molecular Features ◽

Context Specific

Significant improvements with apalutamide, a nonsteroidal antiandrogen used to treat patients suffering from advanced prostate cancer (PCa), have prompted evaluation for additional indications and therapeutic development with other agents; however, persistent androgen receptor (AR) signaling remains problematic. We used autochthonous mouse models of Pten-deficient PCa to examine the context-specific antitumor activity of apalutamide and profile its molecular responses. Overall, apalutamide showed potent antitumor activity in both early-stage and late-stage models of castration-naïve prostate cancer (CNPC). Molecular profiling by Western blot and immunohistochemistry associated persistent surviving cancer cells with upregulated AKT signaling. While apalutamide was ineffective in an early-stage model of castration-resistant prostate cancer (CRPC), it tended to prolong survival in late-stage CRPC. Molecular features associated with surviving cancer cells in CRPC included upregulated aberrant-AR, and phosphorylated S6 and proline-rich Akt substrate of 40 kDa (PRAS40). Strong synergy was observed with the pan-AKT inhibitor GSK690693 and apalutamide in vitro against the CNPC- and CRPC-derived cell lines and tended to improve the antitumor responses in CNPC but not CRPC in vivo. Upregulation of signal transducer and activator of transcription 3 (STAT3) and proviral insertion in murine-1 (PIM-1) were associated with combined apalutamide/GSK690693. Our findings show that apalutamide can attenuate Pten-deficient PCa in a context-specific manner and provides data that can be used to further study and, possibly, develop additional combinations with apalutamide.

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Atypical Granulomatosis with Polyangiitis Presenting with Meibomitis, Scleritis, Uveitis and Papillary Bladder Tumor: A Case Report and Literature Review

Diagnostics ◽

10.3390/diagnostics11040680 ◽

2021 ◽

Vol 11 (4) ◽

pp. 680

Author(s):

Takashi Kojima ◽

Murat Dogru ◽

Eisuke Shimizu ◽

Hiroyuki Yazu ◽

Aya Takahashi ◽

...

Keyword(s):

Granulomatosis With Polyangiitis ◽

Early Stage ◽

Topical Steroid ◽

Granulomatous Inflammation ◽

Oral Prednisolone ◽

Meibomian Gland ◽

Clinical Findings ◽

Meibomian Gland Dysfunction ◽

Oral Steroids ◽

Atypical Cells

Granulomatosis with polyangiitis (GPA) presents with a variety of systemic findings, sometimes with ocular findings initially, but is often difficult to diagnose at an early stage. An 85-year-old male had complaints of ocular dryness and redness and was diagnosed with meibomian gland dysfunction with meibomitis. Despite an initial treatment with topical steroid and antibiotics, the meibomitis did not improve and the left eye developed scleritis and iridocyclitis. The patient was administered topical mydriatics and oral steroids. During follow-up, the patient developed left hearing difficulty and reported a darker urine. Urinalysis revealed microscopic hematuria. A blood test showed an elevated erythrocyte sedimentation rate, positivity for perinuclear anti-neutorophil cytoplasmic antibody, and elevations in blood urea nitrogen and serum creatinine. Nasal mucosal biopsy showed a non-necrotizing granulomatous inflammation. Renal biopsy revealed focal glomerulosclerosis. Cystoscopy and bladder wash followed by a planned transurethral resection revealed atypical cells and apical papillary tumors which were resected. Iridocyclitis and scleritis responded well to oral prednisolone with 0.1% topical betamethasone and prednisolone ointment. The patient is tumor free with no recurrences 24 months after resection. GPA may present atypically with meibomian gland dysfunction without showing representative clinical findings. Early detection and treatment are essential for visual recovery.

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Lung Cancer Inequalities in Stage of Diagnosis in Ontario, Canada

Current Oncology ◽

10.3390/curroncol28030181 ◽

2021 ◽

Vol 28 (3) ◽

pp. 1946-1956

Author(s):

Aisha K. Lofters ◽

Evgenia Gatov ◽

Hong Lu ◽

Nancy N. Baxter ◽

Sara J. T. Guilcher ◽

...

Keyword(s):

Lung Cancer ◽

Relative Risk ◽

Late Stage ◽

Early Stage ◽

Small Cell ◽

Cancer Type ◽

Adjusted Relative Risk ◽

Late Stage Diagnosis ◽

Adjusted Model

Lung cancer is the most common cancer and cause of cancer death in Canada, with approximately 50% of cases diagnosed at stage IV. Sociodemographic inequalities in lung cancer diagnosis have been documented, but it is not known if inequalities exist with respect to immigration status. We used multiple linked health-administrative databases to create a cohort of Ontarians 40–105 years of age who were diagnosed with an incident lung cancer between 1 April 2012 and 31 March 2017. We used modified Poisson regression with robust standard errors to examine the risk of diagnosis at late vs. early stage among immigrants compared to long-term residents. The fully adjusted model included age, sex, neighborhood-area income quintile, number of Aggregated Diagnosis Group (ADG) comorbidities, cancer type, number of prior primary care visits, and continuity of care. Approximately 62% of 38,788 people with an incident lung cancer from 2012 to 2017 were diagnosed at a late stage. Immigrants to the province were no more likely to have a late-stage diagnosis than long-term residents (63.5% vs. 62.0%, relative risk (RR): 1.01 (95% confidence interval (CI): 0.99–1.04), adjusted relative risk (ARR): 1.02 (95% CI: 0.99–1.05)). However, in fully adjusted models, people with more comorbidities were less likely to have a late-stage diagnosis (adjusted relative risk (ARR): 0.82 (95% CI: 0.80–0.84) for those with 10+ vs. 0–5 ADGs). Compared to adenocarcinoma, small cell carcinoma was more likely to be diagnosed at a late stage (ARR: 1.29; 95% CI: 1.27–1.31), and squamous cell (ARR: 0.89; 95% CI: 0.87–0.91) and other lung cancers (ARR: 0.93; 95% CI: 0.91–0.94) were more likely to be diagnosed at an early stage. Men were also slightly more likely to have late-stage diagnosis in the fully adjusted model (ARR: 1.08; 95% CI: 1.05–1.08). Lung cancer in Ontario is a high-fatality cancer that is frequently diagnosed at a late stage. Having fewer comorbidities and being diagnosed with small cell carcinoma was associated with a late-stage diagnosis. The former group may have less health system contact, and the latter group has the lung cancer type most closely associated with smoking. As lung cancer screening programs start to be implemented across Canada, targeted outreach to men and to smokers, increasing awareness about screening, and connecting every Canadian with primary care should be system priorities.

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Topical Application of Ozonated Oils for the Treatment of MRSA Skin Infection in an Animal Model of Infected Ulcer

Biology ◽

10.3390/biology10050372 ◽

2021 ◽

Vol 10 (5) ◽

pp. 372

Author(s):

Vanessa Silva ◽

Cecília Peirone ◽

Rosa Capita ◽

Carlos Alonso-Calleja ◽

José A Marques-Magallanes ◽

...

Keyword(s):

Wound Healing ◽

Animal Model ◽

Topical Application ◽

Early Stage ◽

Bacterial Load ◽

Ozone Treatment ◽

Diabetic Patients ◽

Colony Forming Units ◽

Group 2 ◽

Epidermal Regeneration

Diabetic foot ulcers are a common cause of morbidity in diabetic patients. One of the main pathogens found in these ulcers is methicillin-resistant Staphylococcus aureus (MRSA). MRSA often carries resistance to several classes of antibiotics and their infections are becoming harder to treat. Therefore, new alternatives are urgently needed. Thus, this study aimed to investigate the capacity of topical ozonated oil application on the treatment of early-stage skin infected with MRSA in an animal model. Ozonated oil was prepared from a mixture of oils subjected to a gas stream of O2/O3 mixture. Sixteen Wistar rats were inoculated by an intradermic injection of MRSA suspension, producing an abscess lesion. After 3 days, the skin epidermis was removed to open the wound. Group 1 received an application of oil mixture without ozone treatment and Group 2 received an application of ozonated oil. After the treatment period, skin was collected, colony-forming units (CFU) of bacteria were quantified and the histological analysis of the skin was carried out. Skin samples from the control 1 and 2 had a bacterial load was of 1.1 × 105 and 5.7 × 103 CFU/mL, respectively. Group 2 showed better wound healing from mild to moderate epidermal regeneration. Topical application of ozonated vegetable oil in MRSA-infected skin in rats showed a small reduction of the bacterial load and better wound healing.

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Phase Separation: From the Initial Nucleation Stage to the Final Ostwald Ripening Regime

MRS Proceedings ◽

10.1557/proc-481-125 ◽

1997 ◽

Vol 481 ◽

Author(s):

Celeste Sagui ◽

Dean Stinson O'Gorman ◽

Martin Grant

Keyword(s):

Phase Separation ◽

Late Stage ◽

Ostwald Ripening ◽

Early Stage ◽

Classical Problem ◽

Nucleation And Growth ◽

New Model ◽

Nucleation Stage ◽

Initial Nucleation

ABSTRACTIn this work we have re-examined the classical problem of nucleation and growth. A new model considers the correlations among droplets and naturally incorporates the crossover from the early-stage, nucleation dominated regime to the scaling, late-stage, coarsening regime within a single framework.

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