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On the Ground • We explored private landowner perceptions about the invasive Kentucky bluegrass in the US northern Great Plains. • Landowner responses to a mail survey indicated little to no preventative action. • We also employed a scenario approach to assess landowner perceptions based on changes to ecosystem services. • Scenario results indicated that the early stage of invasion was considered slightly acceptable. At the late stage, when negative impacts are most severe for landowner livelihoods, bluegrass was rated as slightly unacceptable. • Cascading impacts will become more evident and incentivizing early action to prevent further invasion is key to maintaining these working landscapes.

This study evaluated and compared the expression of secreted protein acidic and rich in cysteine (SPARC) in epithelial cells and fibroblasts of oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) using normal oral mucosa as a control.The expression of SPARC was determined in samples of normal oral mucosa (n = 12), OL without dysplasia (n = 31), OL with dysplasia (n = 54), and OSCC (n = 69) using immunohistochemistry. The percentage of positive cells in epithelial cells and fibroblasts was independently evaluated.Epithelial SPARC was found in 33.3%, 35.5%, 25.9%, and 66.7% of normal oral mucosa, OL without dysplasia, OL with dysplasia, and OSCC, respectively. Fibroblast SPARC was found in 50.0%, 29.0%, 46.3%, and 84.1% of normal oral mucosa, OL without dysplasia, OL with dysplasia, and OSCC, respectively. OSCC had higher epithelial and fibroblast SPARC expression than normal oral mucosa, OL without dysplasia, and OL with dysplasia (P.05). No significant differences were observed in epithelial and fibroblast SPARC among normal oral mucosa or OL with and without dysplasia.Overexpression of epithelial and fibroblast SPARC was observed in OSCC but not in OL, suggesting that SPARC is involved in the late stage of oral carcinogenesis.

Introduction Adolescent pregnancy is associated to school desertion, violence, termination of pregnancy under suboptimal conditions, obstetric complications and other consequences that can put the woman's quality of life at risk and of those that surround her. The purpose of this study is to describe the situation and tendencies of adolescent pregnancies, abortions and maternal deaths between 2013 and 2016 in Ecuador. Methods This cross-sectional study uses secondary data from national Ecuadorian vital statistics reports of adolescents between 10 and 19 years old. The data sources used register all the births, deaths and hospital discharges in the country at both public and private health establishments. We performed a descriptive analysis of qualitative and quantitative variables. Results Ecuador has approximately 1.5 million female adolescents that gave birth to 256,561 newborns between 2013 and 2016, resulting in an average annual birth rate in early adolescence of 13.9 live births per 1000 and in late adolescence of 86.6 per 1000 live births. The number of registered abortions among adolescents between 2013 and 2016 was of 19,214. The estimated annual abortion rate in late stage adolescents is 6.3 abortions per 1000 women between 15 and 19. The estimated abortion ratio for this same age group is 72.9 per 1000 live births. Of all the adolescents that gave birth, 84.9% self-identified as mestiza, while 71.9% of Ecuador's general population identifies as such. Only 7% of the general population in Ecuador self-identifies as indigenous, while 21.6% of pregnancies come from this population. Out of all adolescents that gave birth, 57.4% of those aged 17 and over; 43% of those between 14 and 16 and 96.7% of adolescents from 10 to 13, completed the level of education for their age. There were 81 maternal deaths among this group. The maternal mortality rate for late stage adolescents is of 7.72 per 100,000.

Hepatocellular carcinoma (HCC) continues to have a dismal prognosis, with 5-year survival below 20%. This poor prognosis can be in part attributed to failures along the cancer screening process continuum such as underuse of screening in at risk patients and appropriate treatments for patients with HCC. Better understanding these process failures, and how they compare to those seen in other cancer types, can help inform potential intervention targets and strategies to reduce HCC-related mortality. Herein, we outline a conceptual model with several discrete steps in the HCC screening process continuum including risk assessment, screening initiation, follow-up of screening results, diagnostic evaluation, and treatment evaluation. The conceptual model illustrates how each step in the screening process is prone to delays or failure, resulting in worse outcomes such as late stage diagnosis or poor survival, and how factors at the patient, provider, and health care system levels can contribute to these failures. We compare cancer screening processes for HCC with those employed in breast and colorectal cancer screening to identify opportunities for improvement. The Translational Liver Cancer consortium was recently established by the National Cancer Institute with the goal of improving early detection of HCC. Studies designed to address failures in the HCC screening process continuum will help accomplish this goal.

Glyco-polypeptides (Comosain, Bromelain) induced leucocyte binding ability to tumor surface antigens, such as interleukin 2, 6, 8, and TNFs, is known as an immuno-target therapy. Using different concentration of Bromelain proteinases in 6 types of cancer cell, it resulted in hydrolysis, fibrinolysis, necrosis, and anti-metastatic effects in tumor cells. Anti-cancer effects were achieved in carcinoma of lung, breast, colon, ovary, cervix, and uterus. Investigation of anti-metastatic effects in Bromelain were carried out in a double-blind study: low dose cohort was on 10 mg/kg/day and a high dose cohort which was on 50 mg/kg/day for a period of over six months. A total of 83 patients with 3rd and 4th stage of refractory solid tumors were enrolled, whom at least previously failed on two regimens of chemotherapy and/or failed on radiation therapy. The rates of Complete Response (CR) and Partial Responses (PR) in high dose cohort are astonishing with 52% and 27% respectively. The Progress Disease (PD) was 10%, and the Stable Disease (SD) was 11%. The implications and results of the findings are discussed with in view of the reported anti-metastatic activity of orally administrated Bromelain.

INTRODUCTION The estrogen receptor (ER) is a clinically validated oncology target with a pivotal role in hormonally driven breast cancer, the most prevalent form of female cancer. Current treatments which directly modulate ER include antagonists (SERMs), such as tamoxifen, and degraders (SERDs), such as fulvestrant which is administered by intramuscular injection. AREAS COVERED This review covers patent applications that claim estrogen receptor degraders (SERDs) and covalent antagonists (SERCAs) between the period January 2015 to June 2021. A total of 114 patent applications from 23 different applicants are evaluated with stratification into acidic SERDs, basic SERDs and SERCAs. EXPERT OPINION The clinical success of fulvestrant in the treatment of ER+ breast cancer has spurred research over the last decade into the discovery and development of novel SERDs, with a particular focus on the discovery of orally bioavailable drugs. This has resulted in a diverse range of candidates entering clinical trials. Although some have faltered in development, a cohort of oral SERDs has generated encouraging efficacy and safety data that has allowed advancement into late stage clinical trials. Data from these trials is eagerly awaited, with these molecules having the potential to offer significant benefits in the treatment of ER+ breast cancer.

Background: The study involved a female patient diagnosed with late-stage dementia, with chronic daytime somnolence (CDS) as a prominent symptom. Objective: To explore whether her dementia resulted from Type 3 diabetes, and whether it could be reversed through ketosis therapy. Methods: A ketogenic diet (KD) generating low-dose 100 μM Blood Ketone Levels (BKL) enhanced by a brief Ketone Mono Ester (KME) regimen with high-dose 2–4 mM BKLs was used. Results: Three sets of data describe relief (assessed by % days awake) from CDS: 1) incremental, slow, time-dependent KD plus KME-induced sigmoid curve responses which resulted in partial wakefulness (0–40% in 255 days) and complete wakefulness (40–85% in 50 days); 2) both levels of wakefulness were shown to be permanent; 3) initial permanent relief from CDS with low-dose ketosis from 6.7% to 40% took 87 days. Subsequent low-dose recovery from illness-induced CDS (6.9% to 40%) took 10 days. We deduce that the first restoration involved permanent repair, and the second energized the repaired circuits. Conclusion: The results suggest a role for ketosis in the elimination of CDS with the permanent functional restoration of the awake neural circuits of the Sleep-Wake cycle. We discuss whether available evidence supports ketosis-induced bioenergetics alone or whether other mechanisms of functional renewal were the basis for the elimination of CDS. Given evidence for permanent repair, two direct links between ketosis and neurogenesis in the adult mammalian brain are discussed: Ketosis-induced 1) brain-derived neurotrophic factor, resulting in neural progenitor/stem cell proliferation, and 2) mitochondrial bioenergetics-induced stem cell biogenesis.

Some studies suggest that thyroid hormones and disorders can influence breast (BC) and ovarian (OC) cancers risks. However, studies regarding their effect on these tumors progression are limited. Thyroid-stimulating hormone (TSH), T4, free T4 (FT4), T3, and free T3 (FT3) were detected in patients with BC, OC, benign breast and ovary diseases, and healthy controls using highly sensitive chemiluminescence assay. In contrast to OC, hypothyroidism prevalence was associated with BC late stage (11/24 vs. 2/46), high grade (11/23 vs. 4/47), lymph node invasion (11/42 vs. 0/28), positive distant metastasis (11/25 vs. 1/45), and large tumor size (14/25 vs. 1/45) compared to tumor early stages, low grades, negative lymph node, and distant metastasis and small size, respectively. Patients with late stage, high grade, large tumor size, positive lymph nodes, or positive distant metastasis were significantly (P < 0.05) associated with elevated levels of TSH and decreased levels of T4, FT4, T3, and FT3. There were both significant positive correlation of serum TSH and significant inverse correlation of T4, FT4, T3, and FT3 with these tumor worse outcomes. In conclusion, our results identify hypothyroidism as potentially important prognostic factor in BC not in OC that is associated with poor outcomes of BC patients.

Prostate-Specific Membrane Antigen (PSMA) is a credentialed imaging and therapy (theranostic) target for the detection and treatment of prostate cancer. PSMA-targeted positron emission tomography (PET) imaging and molecular radiotherapy (MRT) are promising evolving technologies that will improve the outcomes of prostate cancer patients. In anticipation of this new era in prostate cancer theranostics, this article will review the history of PSMA from discovery, through early and late stage clinical trials. Since 1993, the Prostate Cancer Foundation (PCF) has funded critical and foundational PSMA research that established this theranostic revolution. The history and role of PCF funding in this field will be discussed.

Surveillance of hepatocellular carcinoma (HCC) is beneficial for detecting early-stage HCC. The factors that influence adherence to HCC surveillance and late-stage detection have never been evaluated. We investigated the predictive factors that contribute to patients accessing regular HCC surveillance and their association with the detection of late-stage HCC at the time of diagnosis.We conducted a prospective observational study at Hatyai Hospital (Songkhla, Thailand) between 2014 and 2016. HCC surveillance includes performing hepatic ultrasonography with/without serum alpha-fetoprotein 6-12 months before the detection of HCC. Logistic regression analyses were conducted separately to examine the relationship between the variables and each endpoint.One hundred ninety-nine HCC patients were enrolled in the study; most patients were of low socioeconomic status, 90.5% had less than a bachelor's degree, and 69.3% of patients had a monthly income of10,000 baths (US $312.50). Nearly all (93.5%) patients had cirrhosis, 39.7% had hepatitis B virus (HBV) infection, 24.6% had hepatitis C virus infection, and 24.6% had alcohol-related liver disease. The risk of HCC was recognized in 51.8% of patients, and regular HCC surveillance was achieved in 36.2% of patients. Multivariate logistic regression analysis revealed that a monthly income10,000 baths (US $312.50) (odds ratio [OR], 4.566; p = 0.013), HBV infection (OR, 0.188; p = 0.001), and recognition of patients at risk of HCC (OR, 130.396; p0.001) were independent predictive factors for adherence to HCC surveillance. Regular HCC surveillance (OR, 0.215; p = 0.003) and recognition of HBV infection (OR, 0.356; p = 0.040) were independent preventive factors for the detection of late-stage HCC at the time of diagnosis.In Thailand, awareness of patients at risk of developing HCC and the rate of regular HCC surveillance are low. Greater awareness will enable physicians to surveil and detect HCC.

Epidemiological data show that the incidence rate of cholangiocarcinoma (CCA) has been increasing over the past 20 years. Due to its concealment of clinical manifestations, most patients are diagnosed with CCA at a late stage. On this premise, this review not only discusses the research progress related to CCA diagnosis, but also focuses on the concept of circulating tumor cell (CTC), its evaluation value, application, and prospects for the early diagnosis of extrahepatic cholangiocarcinoma.

Aim: In the late stage of atherosclerosis, the endothelial barrier of plaque is destroyed. The rapid deposition of oxidized lipids in the circulation leads to migration of numerous smooth muscle cells and macrophages, as well as foaming necrosis. The plaque progresses rapidly, and vulnerable plaques can easily induce adverse cardiovascular events. Here, we take the principle of gene editing to transfer the liver to express the LOX-1 receptor which is more sensitive to Ox-LDL by using AAV8 containing a liver-specific promoter. In this way, we want to explore whether the progress of advanced atherosclerosis and the stability of advanced plaque can be improved when the liver continues to clear Ox-LDL from the circulation. Methods and Results: In order to explore the effect of the physiological and continuous elimination of Ox-LDL through the liver on advanced atherosclerosis, we chose ApoE-/- mice in high-fat diet for 20 weeks. After 16 weeks of high-fat diet, the baseline group was sacrificed and the specimens were collected. The virus group and the control group were injected with the same amount of virus dilution and normal saline through the tail vein, and continued to feed until 20 weeks of high-fat diet, and then sacrificed to collect specimens. The results showed that LOX-1 was ectopically and functionally expressed in the liver as an Ox-LDL receptor, reducing the content of it in circulation. Compared with the control group, the degree of plaque progression in the virus group was significantly reduced, similar to the baseline group, the plaque necrosis core decreased, and the collagen fiber content increased. In addition, there are more contractile smooth muscle cells in the plaques of the virus group instead of synthetic ones, and the content of macrophages was also reduced. These data suggested that the virus group mice have greatly increased advanced plaque stability compared with the control group mice. Conclusions: Due to the destruction of endothelial barrier in advanced plaques, rapid deposition of Ox-LDL can result in fast plaque progression, increased necrotic cores, and decreased stability. Our research shows that the use of AAV8 through gene editing allows the liver to express LOX-1 receptors that are more sensitive to Ox-LDL, so that it can continue to bind Ox-LDL in the circulation and exploit the liver's strong lipid metabolism ability to physiologically clear Ox-LDL, which can inhibit the rapid progress of advanced plaque and increase the stability of plaque.

Background: The incidence of anterior cruciate ligament (ACL) injuries have been consistently increasing in adolescents, with those who return to competitive sport having up to a 32% risk of a secondary ACL injury. There is limited evidence regarding knee strength outcomes in young adolescents following ACL reconstruction during late-stage rehabilitation when compared to older patient groups. Purpose: The purpose of this study was to 1) establish normative knee strength values according to age group in adolescent female and male patients during late-stage rehabilitation following ACLR and 2) determine whether strength differences exist between age groups. Methods: A retrospective review of adolescent patients who underwent primary ACL reconstruction was performed. Patients completed a standardized isokinetic (60°/sec) knee extension and flexion strength assessment during late-stage rehabilitation. Peak torque was normalized to the patient’s body mass (Nm/kg) and used to calculate Limb Symmetry Index (LSI). Analyses were conducted separately for female and male cohorts and grouped by early (11-14 years) and middle (15-17 years) adolescence. An independent samples t-test examined strength differences between age groups. Results: 130 females (age=15.4 ± 1.4 years; days since surgery=239.0 ± 84.4) and 112 males (age=15.4 ± 1.5 years; days since surgery= 232.6 ± 91.2) were included. Normalized knee extension peak torque on the involved limb was reported for female (1.5 Nm/kg) and male (1.8 Nm/kg) cohorts. Differences between age groups in knee extension peak torque were found on the surgical and nonsurgical limbs in female (p = 0.02 – 0.05) and male (pConclusion: Early adolescents produced less knee extension and flexion peak torque compared to middle adolescents after ACLR, but no differences were found between age groups when normalized to body mass for female or male cohorts. Normalized knee extension strength in young adolescents may differ from older patients and should be considered in the rehabilitation process. [Table: see text][Table: see text][Table: see text][Table: see text]

The “bullseye” sign has been exclusively reported in patients suffering from coronavirus disease 2019 (COVID-19) pneumonia. It is theorized that this newly recognized computed tomography (CT) feature represents a sign of organizing pneumonia. Well established signs of organizing pneumonia also reported in COVID-19 patients include linear opacities, the “reversed halo” sign (or “atoll” sign), and a perilobular distribution of abnormalities. These findings are usually present on imaging in the intermediate and late stage of the disease. This is a case of simultaneous presence of the “bullseye” and the “reversed halo” sign on chest CT images of a COVID-19 patient examined 22 days after symptom onset.

Cancer has risen up to be a major cause of mortality worldwide over the past decades. Despite advancements in cancer screening and diagnostics, a significant number of cancers are still diagnosed at a late stage with poor prognosis. Hence, the discovery of reliable and accurate methods to diagnose cancer early would be of great help in reducing cancer mortality. Extracellular vesicles (EVs) are phospholipid vesicles found in many biofluids and are released by almost all types of cells. In recent years, using EVs as cancer biomarkers has garnered attention as a novel technique of cancer diagnosis. Compared with traditional tissue biopsy, there are many advantages that this novel diagnostic tool presents - it is less invasive, detects early-stage asymptomatic cancers, and allows for monitoring of tumour progression. As such, EV biomarkers have great potential in improving the diagnostic accuracy of cancers and guiding subsequent therapeutic decisions. Efficient isolation and accurate characterization of EVs are essential for reliable outcomes of clinical application. However, these are complicated by the size and biomolecular diversity of EVs. In this review, we present an analysis and evaluation of the current techniques of EV isolation and characterization, as well as discuss the potential EV biomarkers for specific types of cancer. Taken together, EV biomarkers have a lot of potential as a novel method in cancer diagnostics and diagnosis. However, more work is still needed to streamline the purification, characterization and biomarker identification process to ensure optimal outcomes for patients.

Summary Polyarteritis nodosa is a necrotizing systemic vasculitis of medium caliber arteries whose cause, most often unknown, may be hepatitis B virus. It is a serious condition diagnosed on the basis of well-defined criteria. Clinically, it is manifested by signs of kidney, skin, digestive, cardiac, joint or even vascular damage. The neurological manifestations of polyarteritis nodosa are frequent and make the disease serious. Peripheral neuropathy is the most frequent and earliest symptom. Central nervous system manifestations are less frequent and usually occur at a late stage. The objective of this review article is to describe the clinical manifestations of polyarteritis nodosa with a focus on damage to the central and peripheral nervous system.

The scapholunate ligament is made of 3 portions: proximal, volar, and dorsal. The latter is the major stabilizer of the scapholunar pair, and its lesion is bound to cause a destabilization of the carpus, as well as scapholunar diastasis, dorsal intercalated segment instability, then eventually SLAC (i.e., scapholunate advanced collapse) wrist. The healing process of this ligament, either spontaneous or after primary repair with direct suture, is rarely observed and a significant number of patients are diagnosed only at a late stage, thus making an illusion of a maintained stability of the carpus first range. Management then consists of ligamentoplasty. Several open techniques are described to restore stability, but at the cost of a frequent and significant tightening of the wrist. We will introduce here an arthroscopic ligamentoplasty technique completed by a posterior capsulodesis., Technique Video Video 1 The patient is in the decubitus position, upper limb lies in pronation on an arm table with a pneumatic tourniquet at the basis of the limb, wrist on an arthroscopic tower, right wrist. 00’05: Introduction. 00’22: Ligament check-up and testing. 00’40: Articular check-up. 00’58: Debridement. 01’31: Setting the guide pins. 02’07: Drilling the tunnels. 02’38: Fixation of the SutureTape in the proximal pole of the scaphoid. 03’03: Fixation of the SutureTape in the posterior cornea of the lunate. 03’48: Ligamentoplasty testing through radiocarpal joint. 04’09: Ligamentoplasty testing through midcarpal joint. 04’19: Dorsal capsulodesis.

In the United Arab Emirates (UAE), lung cancer (LC) was the third leading cause of deaths due to cancer in 2017. Around 80% of the patients in the UAE are diagnosed at a late stage, rendering the treatment less effective in improving survival outcomes. Lack of awareness of disease symptomatology, deficient screening initiatives, misdiagnosis, and delayed referral to the specialist are contributing factors for delayed diagnosis. Effective screening at a primary care setting can be crucial for early diagnosis, referral to specialists, and enhancing patient outcomes. It is important to establish screening and referral guidelines through which each suspected case can be identified and provided timely intervention. Although the international screening and referral pathway framework are comprehensive, several regional barriers need to be addressed before they can be adapted at the national level. A group of LC experts from the UAE deliberated on issues like delayed diagnosis of LC and strategic recommendations for overcoming the challenges. The discussion was based on the review of the published evidence, international and regional guidelines for screening and early diagnosis of LC. Herein, we present a guideline, endorsed by the esteemed panel of experts, for aiding early diagnosis and optimizing the management of LC in the UAE.

Purpose The exact nature of sex and gender differences in knee osteoarthritis (OA) among patient candidates for total knee arthroplasty (TKA) remains unclear and requires better elucidation to guide clinical practice. The purpose of this investigation was to survey physician practices and perceptions about the influence of sex and gender on knee OA presentation, care, and outcomes after TKA. Methods The survey questions were elaborated by a multidisciplinary scientific board composed of 1 pain specialist, 4 orthopedic specialists, 2 physiatrists, and 1 expert in gender medicine. The survey included 5 demographic questions and 20 topic questions. Eligible physician respondents were those who treat patients during all phases of care (pain specialists, orthopedic specialists, and physiatrists). All survey responses were anonymized and handled via remote dispersed geographic participation. Results Fifty-six physicians (71% male) accepted the invitation to complete the survey. In general, healthcare professionals expressed that women presented worse symptomology, higher pain intensity, and lower pain tolerance and necessitated a different pharmacological approach compared to men. Pain and orthopedic specialists were more likely to indicate sex and gender differences in knee OA than physiatrists. Physicians expressed that the absence of sex and gender-specific instruments and indications is an important limitation on available studies. Conclusions Healthcare professionals perceive multiple sex and gender-related differences in patients with knee OA, especially in the pre- and perioperative phases of TKA. Sex and gender bias sensitivity training for physicians can potentially improve the objectivity of care for knee OA among TKA candidates.

This article is a maiden attempt at exploring determinants of stage-specific investment choices of Indian venture capital and private equity (VCPE) firms. Analysis of 5,782 VCPE investment deals during 1998–2016 shows that firms’ preferences to invest in various stages (early vs. late) are significantly affected by the characteristics of the VCPE firms, features of the deal, and characteristics of the investee firms. More specifically, experience and ownership (foreign vs. domestic) of VCPE firm, type of deal (syndicated or otherwise), investment size of the deal, and location and industry of the investee firm influence the stage of investment. Detailed empirical analysis shows that younger VCPE firms and those with domestic investors prefer to invest in early stages, presumably because they wish to build a reputation and also leverage their proximity with investee firms to manage high market and technological risks associated with early-stage investments. Syndication is another mechanism used to manage the risks associated with early-stage deals. Investee firms in industries that have lower investment requirements or shorter gestation periods and those located in regions with a mature entrepreneurial ecosystems are more likely to attract early-stage investments. JEL Classification: G24, L26, D81

Tumor recurrence after surgery is the main cause of treatment failure. However, the initial stage of recurrence is not easy to detect, and it is difficult to cure in the late stage. In order to improve the life quality of postoperative patients, an efficient synergistic immunotherapy was developed to achieve early diagnosis and treatment of post-surgical tumor recurrence, simultaneously. In this paper, two kinds of theranostic agents based on gold nanorods (AuNRs) platform were prepared. AuNRs and quantum dots (QDs) in one agent was used for the detection of carcinoembryonic antigen (CEA), using fluorescence resonance energy transfer (FRET) technology to indicate the occurrence of in situ recurrence, while AuNRs in the other agent was used for photothermal therapy (PTT), together with anti-PDL1 mediated immunotherapy to alleviate the process of tumor metastasis. A series of assays indicated that this synergistic immunotherapy could induce tumor cell death and the increased generation of CD3+/CD4+ T-lymphocytes and CD3+/CD8+ T-lymphocytes. Besides, more immune factors (IL-2, IL-6, and IFN-γ) produced by synergistic immunotherapy were secreted than mono-immunotherapy. This cooperative immunotherapy strategy could be utilized for diagnosis and treatment of postoperative tumor recurrence at the same time, providing a new perspective for basic and clinical research., Graphical abstract This efficient synergistic immunotherapy was developed to achieve early diagnosis and treatment of post-surgical tumor recurrence, simultaneously.Image 1

Introduction: Polycythemia vera is a chronic hematologic malignancy frequently presented with constitutional symptoms and associated with an increased risk of thrombosis, hemorrhage, and progression to myelofibrosis or acute myeloid leukemia. Current treatment strategies reduce thrombohemorrhagic risk by controlling blood counts and inhibiting platelets, but often fail to address disease-related symptoms or biologically modify the disease.Areas covered: We review the current paradigm for treating polycythemia vera, highlight areas of unmet need, review therapeutic agents in late stage clinical development, and provide an overarching view of how these emerging agent may fit into the future armamentarium of polycythemia vera treatments.Expert opinion: The shift from focusing solely on secondary prevention of thrombohemorrhagic events to a comprehensive treatment strategy that additionally aims to improve quality of life and prevent disease progression has resulted in a rapidly evolving therapeutic landscape that promises to move the treatment of polycythemia vera out of antiquity into the modern age.

Colorectal cancer (CRC) in adults

With multimodal visualization of the chorioretinal complex structures using modern research methods, it was possible to isolatea mixed, or combined, phenotype of the late stage of age-related macular degeneration (AMD). Early detection of this AMD form is of vital importance not only for accurate diagnosis, but for choosing optimal management tactics for patients. The paper presents two clinical cases with different variants of the development of the mixed phenotype of the late AMD stage. In one case, the long-lasting “geographic atrophy” (GA) was complicated by the development of choroidal neovascularization, while in the other case GA appeared during the treatment of wetAMD.

This retrospective investigated the impact of donor age, recipient age, donor endothelial cell density, vis-à-tergo, and additional intraoperative lens exchange (triple-procedure) on overall early and late phase postoperative endothelial cell density (ECD) following penetrating keratoplasty (PKP) in various diagnosis groups.In 590 cases with diagnosed keratoconus (KC), Fuchs dystrophy (FD) and herpes simplex virus infection (HSV) who underwent PKP or triple surgery, the ECD in cells/mmCorrelation analysis demonstrated a weak negative correlation between the patient's ECD and donor age (early postoperative stage: r = - 0.25, p 0.001; after last suture removal: r = - 0.16; p = 0.003). Regression analysis revealed that donor age did not impact postoperative patient ECD. There was a weak negative correlation between postoperative ECD and recipient age (early postoperative stage: r = - 0.31, p 0.001; after last suture removal: r = - 0.34, p 0.001). Regression analysis confirmed the negative impact of recipient age on patient ECD (early postoperative stage: β = - 13.2, p = 0.001; after last suture removal: β = - 4.6, p 0.001). Correlation analysis determined a weak positive correlation between postoperative ECD and donor endothelial cell density (early postoperative stage: r = 0.37, p 0.001; after last suture removal: r = 0.32, p 0.001). Regression analysis also determined that donor endothelial cell density had a positive impact on postoperative ECD following last suture removal (β = 0.4, p 0.001). Vis-à-tergo and additional lens exchange (triple procedure) had no significant effect on postoperative ECD (p 0.05). This was also confirmed by the results of the regression analysis after last suture removal.Recipient age and donor endothelial cell density have a significant impact on postoperative ECD following PKP. Not all of the statistical tests proved donor age to be a significant influencing factor. Vis-à-tergo and additional lens exchange (triple procedure) had no significant effect on postoperative ECD following PKP.Ziel dieser retrospektiven Arbeit war es, den Einfluss des Spenderalters, des Empfängeralters, der Spenderendothelzelldichte, der Vis-à-tergo und des zusätzlichen Linsenaustausches (Triple Procedure) auf die postoperative Endothelzelldichte (EZD) insgesamt und im Zusammenhang mit zugrunde liegenden Erkrankungen in der Früh- und Spätphase nach perforierender Keratoplastik (PKP) zu untersuchen.Bei 590 Fällen mit den Diagnosen Keratokonus (KK), Fuchs-Dystrophie (FD) und Herpesvireninfektion (HSV), die eine PKP oder eine Triple-Operation erhalten haben, wurde präoperativ, mit liegenden Fäden früh postoperativ und nach Komplettfadenentfernung die EZD in Zellen/mmZwischen der EZD des Patienten und dem Spenderalter zeigte sich in der Korrelationsanalyse ein schwach negativer Zusammenhang (früh postoperativ: r = − 0,25; p 0,001; nach Komplettfadenentfernung: r = − 0,16; p = 0,003). Die Regressionsanalyse ergab, dass das Alter des Spenders die postoperative EZD nicht beeinflusst. Die EZD des Patienten korrelierte schwach negativ mit dem Empfängeralter (früh postoperativ: r = − 0,31; p 0,001; nach Komplettfadenentfernung: r = − 0,34; p 0,001). Die Regressionsanalyse bestätigte, dass die EZD des Patienten durch das Empfängeralter zu beiden postoperativen Zeitstadien negativ beeinflusst wird (früh postoperativ: β = − 13,2; p = 0,001; nach Komplettfadenentfernung: β = − 4,6; p 0,001). In der Korrelationsanalyse wurde ein schwach positiver Zusammenhang zwischen der postoperativen EZD und der Spenderendothelzelldichte festgestellt (früh postoperativ: r = 0,37; p 0,001; nach Komplettfadenentfernung: r = 0,32; p 0,001). Auch die Regressionsanalyse ergab, dass die Spenderendothelzelldichte die postoperativen EZD nach Komplettfadenentfernung positiv beeinflusst (β = 0,4; p 0,001). Die Einflussfaktoren Vis-à-tergo und Triple-Operation zeigten keinen signifikanten Einfluss auf die postoperative EZD (p 0,05). Dies bestätigten auch die Ergebnisse der Regressionsanalyse nach der Komplettfadenentfernung.Empfängeralter und Spenderendothelzelldichte haben signifikant Einfluss auf die postoperative EZD nach PKP. Das Spenderalter kann nicht in allen Tests als signifikante Einflussgröße nachgewiesen werden. Die Vis-à-tergo und die Triple-Operation haben keinen signifikanten Einfluss auf die postoperative EZD nach PKP.

Purpose This study aimed to describe the choroidal features of ocular amyloidosis using multimodal imaging, to correlate these findings with systemic involvement, and to propose a choroidal grading system. Methods Eleven patients with systemic amyloidosis were reviewed retrospectively. Each case was assigned a grade according to the severity of choroidal findings as determined by both enhanced depth imaging optical coherence tomography and indocyanine green angiography. The severity of systemic amyloidosis was then correlated with the choroidal involvement. Results On indocyanine green angiography, all patients exhibited hyperfluorescent spots in the late stage and were classified according to preexisting criteria. On enhanced depth imaging optical coherence tomography, hyperreflective foci were seen in the choriocapillaris and Sattler's layer in Grade 1, partial loss of Sattler's layer was additionally seen in Grade 2, and a dense hyperreflective Haller's layer was seen in Grade 3. Choroidal grading scores were significantly correlated with the systemic severity score (P = 0.0014, Pearson's correlation coefficient; ρ = 0.83). Conclusion With ocular amyloidosis, evaluation of choroidal characteristics using multimodal imaging may serve as a biomarker for systemic involvement.

Background: Secondary lymphedema (LE) can occur after breast cancer (BC) therapy with axillary lymph node surgery and/or radiotherapy. Reported incidence varies around 20%. The aim of this study was to see whether low-energy extracorporeal shockwave therapy (ESWT) is a therapeutic option in end-stage secondary upper limb fibro-LE. Methods and Results: A pilot study was performed on 10 adult patients who presented with an end-stage LE after BC treatment. They were all treated with usual physical therapy and all had lymphatic surgery before. Eight sessions of ESWT were applied, 2600 shocks at 0.1 mJ/mm2, 2/week during 4 weeks. Upper limb volume decreased nonsignificantly, from 3086.4 ± 539.47 to 2909.1 ± 471.60 mL. Mean circumference of the upper limb was significantly decreased from 32.3 ± 3.01 to 31.4 ± 2.71 cm at the height of the upper arm, from 29.1 ± 2.89 to 28.1 ± 2.71 cm at the height of the elbow, and from 27.5 ± 4.08 to 26.8 ± 3.75 cm at the height of the forearm. Subjective measurements by visual analog scale showed significant decrease in both hardness from 57.3 ± 15.84 to 24.4 ± 21.89 mm and subjective feeling of edema from 44.2 ± 16.90 to 23.2 ± 21.16 mm. No adverse features were reported. Conclusion: We added some evidence that low-energy ESWT is well supported and has additional benefits also in longstanding fibro-lipo-LE on swelling of the arm leading to more subjective comfort for the patients.

Traditionally, the efficacy of novel cancer therapies has been confirmed in patients failing regular treatment before being tested in early disease. Improved understanding of the mechanisms guiding therapeutic efficacy may challenge this dogma, suggesting novel therapies to move into early evaluation based on biological rationales without late-stage efficacy evaluation.

Ovarian fibrothecoma is a rare, benign neoplasm of the sex cords and stroma of the ovary. Patients may present with abdominal pelvic pain and / or distension, and sometimes postmenopausal bleeding. Large tumors (> 10cm) are often associated with pleural and peritoneal effusion mimicking an advanced ovarian malignancy (Deimon –Meigs syndrome). We report 2 cases of giant fibrothecoma associated with ascites and pleurisy. Both patients were postmenopausal. The ovarian tumor was discovered during an increase in abdominal volume in the first patient and as part of the etiological workup of encysted pleurisy in the second. The clinical examination made it possible to objectify a tumor with abdominopelvic development of size greater than 10 cm, the clinical examination also noted, in the two patients, a right basithoracic dullness in favor of a pleurisy and an ascites of average abundance suggesting in the first place a malignant tumor of the ovary, with peritoneal carcinoma. the two patients underwent a pelvic ultrasound, supplemented by an abdominal pelvic CT scan objectifying the presence of a large ovarian mass with pleural and peritoneal effusions. Exploratory laparotomy was required in both patients and underwent an extemporaneous examination which was consistent with the definitive pathological examination in both patients. Both patients underwent total hysterectomy with bilateral adnexectomy and omentectomy with multiple biopsies as the clinical picture was highly suggestive of malignancy. The postoperative follow-up was simple with total regression of peritoneal and pleural effusions in the two cases of Demons-Meigs syndrome. The definitive pathological examination revealed a fibrothecoma. Fibrothecal tumors remain a real challenge from a diagnostic and therapeutic point of view. The fear of cancer is even greater in the presence of Demons-Meigs syndrome. The management of these tumors requires a good clinical and radiological analysis, and it is the histological examination that confirms the diagnosis. The surgery corresponds, in post-menopausal patients, to a hysterectomy with bilateral adnexectomy, while conservative treatment by unilateral adnexectomy is entirely justified in young women who still want fertility.

Introduction Healthcare-associated infections caused by multidrug-resistant Acinetobacter baumannii are becoming alarming worldwide. However, the pipeline of new antibiotics is very limited. Vaccination is one of the most cost effective and promising strategies to prevent infections and can play an important role in combat multidrug resistance A. baumannii and prevent the development of new drug resistance. Area covered This review gives an overview of the research and development of A. baumannii vaccines during the past five years (2015–2020), discusses the key progresses and current challenges of the field, and speculates on the future of A. baumannii vaccine development. Expert opinion Moderate progresses have been made in the research and development of A. baumannii vaccine in the last five years, in particular in the areas of identification of new protein targets, development of multicomponent vaccines, and use of vaccines and antibodies as adjuncts for antibiotics therapies. However, substantial scientific and logistic challenges, such as selection of lead vaccine candidates and formulation, vaccine clinical trials and targeted population, and financial incentives, remain. Thus, innovative strategies will be needed before an A. baumannii vaccine candidate can be brought into late stage of preclinical development in next five years.

Objective Colorectal cancer (CRC) is the fourth leading cause of mortality in Oman, with most patients diagnosed at advanced stages. Early diagnosis of CRC improves prognosis and survival rate. The aim of this study was to explore the symptom perceptions and help-seeking behaviours (HSBs) of Omani patients diagnosed with late-stage CRC. Methods Semi-structured individual interviews were conducted with 16 patients. Results Four main themes emerged, including normalisation and ignorance (patients felt healthy, perceived symptoms as not being serious and related to dietary habits, concealed them or prioritised work and family commitments), self-empowerment and self-management (patients were stubborn, employed 'wait and see' approach, used symptomatic or herbal treatments), disclosure and seeking help (patients disclosed symptoms to family members or friends, sought medical help only when symptoms worsened, visited faith healers or travelled abroad for treatment) and healthcare professionals (patients attributed treatment or diagnosis delays to lack of continuity of care, loss of trust in doctors or delays in referral). Conclusion Patients attributed delays in CRC diagnosis to several factors based on their perceptions of symptoms. Most HSBs driven by sociocultural and emotional causes. Increased awareness of CRC symptoms and modifying HSBs can encourage early diagnosis. Prompting patients to disclose CRC-related symptoms may aid referral decisions.

Background A comprehensive battery of tests are used to inform return to play decisions following anterior cruciate ligament (ACL) reconstruction. Performance measures contribute to patient function, but it is not clear if achieving symmetrical performance on strength and hop tests is sufficient or if a patient also needs to meet minimum unilateral thresholds. Hypothesis/Purpose To determine the association of quadriceps strength and single-leg forward hop performance with patient-reported function, as measured by the IKDC Subjective Knee Form (IKDC), during late-stage ACL rehabilitation. A secondary purpose was to determine which clinical tests were the most difficult for participants to pass. Study Design Descriptive Laboratory Study Methods Forty-eight individuals with a history of ACL-R (32 female, 16 male; mean±SD age=18.0±2.7 y; height=172.4±7.6 cm; mass=69.6±11.4 kg; time since surgery=7.7±1.8 months; IKDC=86.8±10.6) completed the IKDC survey, quadriceps isometric strength, and single-leg forward hop performance. The relationship between IKDC scores and performance measures (LSI and involved limb) was determined using stepwise linear regression. Frequency counts were used to determine whether participants met clinical thresholds (IKDC ≥ 90%, quadriceps and single-leg forward hop LSI ≥ 90%, quadriceps peak torque ≥ 3.0 Nm/kg, and single-leg forward hop ≥ 80% height for females and ≥ 90% height for males). Results Quadriceps LSI and involved limb peak torque explained 39% of the variance in IKDC scores while measures of single-leg forward hop performance did not add to the predictive model. Nearly 90% of participants could not meet established clinical thresholds on all five tests and quadriceps strength (LSI and peak torque) was the most common unmet criteria (71% of participants). Conclusions During late-stage ACL rehabilitation deficits in quadriceps strength contribute more to patient function and are greater in magnitude compared to hop test performance. Level of evidence Cross-Sectional Study, Level 3, This study investigates the association of quadriceps strength and single-leg forward hop performance with patient-reported function, during late-stage ACL rehabilitation, as well as which tests are more difficult to pass.

Automated reactor and sampling technologies were used in process characterization studies of a cyclization reaction using gaseous ammonia. These data-rich experiments were structured according to a...

Background Achalasia is a chronic motility disorder which may require surgical interventions to effectively manage patients’ symptoms and improve functional status. In late stage achalasia, patients may present with sigmoid-shaped esophagus which complicates traditional treatment approaches for achalasia as the esophagus is massively dilated and dysfunctional with delicate tissue integrity. Severe Achalasia with sigmoid esophagus imposes significant challenge to surgeons and treating physicians. Various assessment modalities and treatment approaches have been tried. Surgical treatment continues to be controversial. Some have argued that a less aggressive approach similar to that in early Achalasia results in satisfactory outcomes. Others have argued a more aggressive approach of esophagectomy is necessary. We present a review of the challenges encountered in each approach with recommendation for selecting the right treatment for the individual cases. Conclusions Different treatment options for sigmoid type achalasia are available with ongoing controversy among the options. Heller myotomy with Dor fundoplication can provide satisfactory symptoms improvement and treatment outcomes., Highlights • Late stage achalasia may present with sigmoid-shaped esophagus. • Sigmoid shaped esophagus imposes significant treatment challenges due to dilation and delicate tissue integrity. • Surgical treatment continues to be controversial. • Heller myotomy with Dor fundoplication can provide satisfactory symptoms improvement and treatment outcomes.

Developmental dysplasia of hip is a disorder of abnormal development of the hip joint resulting early osteoarthritis of the hip. In late stage of disease, total hip arthroplasty is the option to reduce pain. Total hip arthroplasty in development dyplastic hip is a very challenging procedure in view of abnormal anatomy and biomechanic of the hip. A proper pre-operative planning is important of successful surgery. We report a case of a 60-year-old woman with neglected DDH with severe hip pain, who underwent total hip replacement with good result.

Age-related macular degeneration (AMD) is a chronic, multifactorial disease and a leading cause of irreversible blindness in the elderly population in the Western Hemisphere. Among the two major subtypes of AMD, the prevalence of the nonneovascular (dry) type is approximately 85-90% and the neovascular (wet) type is 10-15%. Healthy lifestyle and nutritional supplements of anti-oxidative micronutrients have been shown to delay the progression of dry AMD and lower the risk of development of wet AMD, and anti-vascular endothelial growth factor (anti-VEGF) injections have been shown to improve visual acuity for wet AMD patients. However, to date, there is no approved treatment for geographic atrophy (GA), a debilitating late stage of dry AMD. Thus, this represents a large unmet need in this patient population. This review focuses on the current management and treatment of nonneovascular AMD, the drugs and devices that have been under investigation for the treatment of GA, and the latest clinical trial results. A few therapeutic options have shown initial promising clinical trial results, but failed to show efficacy in larger trials, while others are awaiting future clinical trial results and long-term follow-up to evaluate safety and efficacy.

Spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS) share a common molecular basis: both are associated with CAG-repeat expansion of ATXN2 and TDP-43-positive neuronal cytoplasmic inclusions. To date, the two disorders are viewed as clinically distinct with ALS resulting from 30-33 CAG-repeats and SCA2 from >34 CAG-repeats. We describe a 67-year old with a 32 CAG-repeat expansion of ATXN2 who presented with simultaneous symptoms of ALS and SCA2. Our case demonstrates that the clinical dichotomy between SCA2 and ATXN2-ALS is false. We suggest instead that CAG-repeat expansion length determines the timing of SCA2 clinical symptoms relative to onset of ALS; consistent with this age of onset of SCA2 but not ATXN2-ALS, is dependent upon expansion length. Review of the literature and our local cohort provides evidence for occurrence of ALS in late stage SCA2, which may be under-recognised by clinicians who think of the two diseases as distinct.

User research in all its forms—from early ethnographic studies to late stage usability validation studies— undoubtedly can add value to any product design and development process. At its best, user research is tightly integrated with the design process, and designers and other team members eagerly seek out research findings to guide design decisions. At its worst, user research can hinder rather than help the efforts of the larger product design and development team—answering the wrong questions, providing misleading information, and focusing attention on issues that are not critical to product success. This can lead to friction between researchers and designers and other members of the product development team. This panel addresses the challenges of integrating user research into the product development process in a way that truly adds value, while suggesting ways to avoid common pitfalls that can result in user research leading designers astray.

Oral cancer is a major health problem in India. The use of tobacco in various forms has escalated the problem to be the leading cause of cancer in males in India. Many patients postpone surgery for fear of facial mutilation and therefore present with Late stage Buccal Cancer. The management of Late stage buccal cancer has very few options. Conventional surgery, chemotherapy and radiation give very little relief to patients. The occurrence of inevitable recurrence after surgery due to Field cancerisation makes the surgery a futile exercise in controlling the spread of the tumor. The treatment in unresectable tumors which is given as palliation is often limited to pain control and bypassing of oral functions by inserting a nasogastric tube. The mortality rate has remained changed over last 10 years. Therefore Quality of life in these patients has become a discussion matter in most cancer forums. The main cause of the suffering of the patient is the bulk of the tumour. Intralesional Laser ablation offers an alternative way to destroy the bulk of the tumor. The reduction in tumor volume allows good restitution of oral function and pain. There were 49 patients observed in this study. Many patients went into remission after laser ablation and Chemotherapy. The ensuing results were analyzed taking into account Quality and Quantity of life and the resulting Quality index was applied on the patients. Most patients had a good Quality Index post-procedure. All patients were highly satisfied with the procedure. There was an enhanced benefit noted in the quality of life and the expected overall survival time of the patients. Conclusion: Laser Ablation offers an alternative treatment in late-stage Oral Cancer for palliation as well as remission.

As vixotrigine (1) entered a later clinical phase for trigeminal neuralgia (Zakrzewska, J. M.; et al. Lancet Neurol. 2017, 16, 291−300), the development of a sustainable late-stage process was requ...

To investigate the mental state of medical imaging staff in Shandong Province, China, who have been on the forefront of the COVID-19 epidemic during its late stage in China. Questionnaires designed to assess anxiety and depression were administered on-location, and 5331 complete results were collected. SPSS software was used for statistical descriptions and analysis. Rates of anxiety disorders and depression among medical imaging workers in Shandong Province, China, were 6.1% and 6.5%, respectively, higher than those of anxiety and depression in Chinese residents before the epidemic. The outbreak in Xinjiang, China; virus mutation in Japan; and spread of the epidemic due to occupational errors were the primary reported causes of anxiety and depression among image workers. Medical imaging workers showed evidence of psychological abnormalities during the late stage of the epidemic in China.

Background: The Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) is an increasingly utilized cognitive stress test designed to identify early cognitive changes associated with incipient neurodegenerative disease. Objective: To examine previously derived cut-points for cognitively unimpaired older adults that were suggestive of performance impairment on multiple subscales of the LASSI-L. These cut-points were applied to a new sample of older adults who were cognitive healthy controls (HC: n = 26) and those on the Alzheimer’s disease (AD) continuum from early stage mild cognitive impairment (EMCI: n = 28), late stage MCI (LMCI: n = 18) to mild AD (AD: n = 27). Methods: All participants were administered the LASSI-L. All cognitively impaired participants were PET amyloid positive which likely reflects underlying AD neuropathology, while cognitively normal counterparts were deemed to have amyloid negative scans. Results: There was a monotonic relationship between the number of deficits on LASSI-L subscales and independent classification of study groups with greater severity of cognitive impairment. Importantly, taken together, impairment on maximum learning ability and measures of proactive semantic interference (both reflected by cued recall and intrusion errors) correctly classified 74.1% of EMCI, 94.4% of LMCI, and 96.3% of AD. Only 7.7% of HC were incorrectly classified as having impairments. Conclusion: A modest number of LASSI-L subscales taking approximately 8 minutes to administer, had excellent discriminative ability using established cut-offs among individuals with presumptive stages of AD. This has potential implications for both clinical practice and clinical research settings targeting AD during early prodromal stages.

Co-authors received external funding linked to the project, but these are non-UK based and not at DMU. The financial support from the National Natural Science Foundation of China (No.72174163, No. 71974026, No. 71804140 and No. 71672138) is gratefully acknowledged. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Where venture capitalists have traditionally focused on early-stage innovative firms, increasingly venture capitalists are investing in late-stage firms, especially in Asia. The performance consequences of this novel phenomenon of late-stage venture capital remain unexplored. This paper provides novel insight into this phenomenon by examining the impact of late-stage venture capital on two key dimensions of firm performance in the venture capital literature: innovation and financial performance. We link VC investment events to financial indicators of Chinese listed firms to account for the timing of VC entry and identify the firm performance impacts. Utilizing a matching and difference-in-differences procedure to account for selection biases, our results show that late-stage venture capital improves investee firms’ financial performance but reduces their innovation performance. Our findings advance understanding about the emergence of late-stage venture capital and its performance consequences, especially in emerging economies. Our work has implications for entrepreneurs and policymakers.

Aims Pre-registration of study protocols in accessible databases is required for publication of study results in high-impact medical journals. Nonetheless, data on characteristics of clinical trials registered in these databases and their outcome, in terms of result reporting and publication are limited. Methods and results We searched for interventional, late-phase cardiovascular disease (CVD) studies in adults registered in Clinicaltrials.gov. first posted after 1 January 2013 and completed up to 31 December 2018. Data on study design, result reporting, and publication were collected, and potential associations with a pre-defined set of explanatory factors were examined. In total, 250 CVD trials were included in the analysis. Of these, 193 (77.2%) were randomized studies, 99 (39.6%) open label designs, and 126 (50.4%) had industry as main sponsor. One hundred and seventy-nine trials (71.6%) evaluated the effect of drugs and 27 (10.8%) evaluated devices. The most common primary outcomes were non-clinical endpoints (76.0%), with only 17% of studies evaluating clinical endpoints. Industry-funded trials focused on patent-protected drugs and devices more often than non-industry-funded trials (72.0% vs. 30.6%, P Conclusion Among late-stage cardiovascular trials only one-fourth had results posted on clinicaltrials.gov and

Objective The aim of this study was to investigate the roles of SMURF1 and SMURF2 in progenitor cells from the human knee in late-stage osteoarthritis (OA). Design We applied immunohistochemistry, immunocytochemistry, RNAi, lentiviral transfection, and Western blot analysis. We obtained chondrogenic progenitor cells (CPCs) from the articular cartilage and meniscus progenitor cells (MPCs) from the nonvascularized part of the meniscus. Results SMURF1 and SMURF2 appeared in both osteoarthritic tissues. CPCs and MPCs exhibited comparable amounts of these proteins, which influence the balance between RUNX2 and SOX9. The overexpression of SMURF1 reduced the levels of RUNX2, SOX9, and TGFBR1. The overexpression of SMURF2 also reduced the levels of RUNX2 and TGFBR1, while SOX9 levels were not affected. The knockdown of SMURF1 had no effect on RUNX2, SOX9, or TGFBR1. The knockdown of SMURF2 enhanced RUNX2 and SOX9 levels in CPCs. The respective protein levels in MPCs were not affected. Conclusions This study shows that SMURF1 and SMURF2 are regulatory players for the expression of the major regulator transcription factors RUNX2 and SOX9 in CPCs and MPCs. Our novel findings may help elucidate new treatment strategies for cartilage regeneration.

Background Anterior cruciate ligament injuries are among the most common knee injuries. Mechanism of injury is classified as contact or non-contact. The majority of anterior cruciate ligament ruptures occur through a non-contact mechanism of injury. Non-contact anterior cruciate ligament ruptures are associated with biomechanical and neuromuscular risk factors that can predispose athletes to injuries and may impact future function. Non-contact mechanism of injury may be preceded by poor dynamic knee stability and therefore those with a non-contact mechanism of injury may be prone to poor dynamic knee stability post-operatively. Understanding how mechanism of injury affects post-operative functional recovery may have clinical implications on rehabilitation. Purpose The purpose of this study was to determine if mechanism of injury influenced strength, functional performance, patient-reported outcome measures, and psychological outlook in athletes at four time points in the first two years following anterior cruciate ligament reconstruction. Study design Secondary analysis of a clinical trial. Methods Seventy-nine athletes underwent functional testing at enrollment after impairment resolution. Quadriceps strength, hop testing, and patient-reported outcome measures were evaluated post-operatively at enrollment, following return-to-sport training and one year and two years after anterior cruciate ligament reconstruction. Participants were dichotomized by mechanism of injury (29 contact, 50 noncontact). Independent t-tests were used to compare differences between groups. Results There were no meaningful differences between contact and non-contact mechanism of injury in any variables at enrollment, post-training, one year, or two years after anterior cruciate ligament reconstruction. Conclusion Function did not differ according to mechanism of injury during late stage rehabilitation or one or two years after anterior cruciate ligament reconstruction. Level of evidence III.

Aim: The aim of this study is to compare the risk factors, management and pregnancy outcome between the Gestational Diabetes Mellitus (GDM) patients who were diagnosed at early and late stage of pregnancy. Methods: We randomly selected 250 newly detected GDM patients and examined them. They were divided into two groups considering the gestational age at the time of diagnosis: early group (13 to 28 weeks) and late group (after 28 weeks). Results: Data of 150 cases from early group and 100 cases from late group were analyzed. Incidence of nulliparous GDM patient (24% vs 36%, P – 0.04),weight at the time of GDM diagnosis (66.0 ± 11.067 vs 69.93 ± 9.865, P - 0.004) were significantly higher in late group and so was the excess body weight from ideal body weight (14.13 ± 10.147 vs 17.94 ± 8.535, P - 0.002). Prevalence of pre pregnancy obese/ overweight patients (68.7% vs 80.0%, P - 0.047), maternal H/O of DM (45.3% vs 32%, p - 0.035) and H/O unexplained fetal loss (24% vs 10%, p - 0.005) were higher in early group. There were no significant differences of blood sugar values (SMBG) between the groups except fasting blood sugar at 2nd visit (F2) (5.557 ± 1.045 vs 5.167 ± 0.960, P - 0.01). Conclusion: This study suggests that range of screening should be broader to detect high risk and undiagnosed GDM mothers. Beside that it has also showed that only early diagnosis and intervention will not be enough to prevent the complications if the patients fails to understand and participate in GDM management.