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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.

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.

J.R. and G.A.B. thank GlaxoSmithKline (GSK) and the Engineering and Physical Sciences Research Council (EPSRC) for an industrial CASE studentship. MMA is supported by a studentship from the government of Libya, and MAU by a studentship from the Petroleum Technology Development Fund (PTDF), Abuja, Nigeria. A selective mono-N-arylation strategy of amidines under Chan-Lam conditions is described. During the reaction optimization phase, the isolation of a mononuclear Cu(II) complex provided unique mechanistic insight into the operation of Chan-Lam mono-N-arylation. The scope of the process is demonstrated, and then applied to access the first mono-N-arylated analogues of pentamidine. Sub-micromolar activity against kinetoplastid parasites was observed for several analogues with no cross-resistance in pentamidine and diminazene-resistant trypanosome strains and against Leishmania mexicana. A fluorescent mono-N-arylated pentamidine analogue revealed rapid cellular uptake, accumulating in parasite nuclei and the kinetoplasts. The DNA binding capability of the mono-N-arylated pentamidine series was confirmed by UV-melt measurements using AT-rich DNA. This work highlights the potential to use Chan-Lam mono-N-arylation to develop therapeutic leads against diamidine-resistant trypanosomiasis and leishmaniasis. Publisher PDF

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.

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.

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 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.

Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide, which usually presents at a late stage and has a poor prognosis. Thus, there is an urgent need for the development of an effective and reliable imaging method for detection and surgical navigation. Most modern imaging technologies, such as super-resolution microscopy and single-molecule localization microscopy, utilize traditional dyes, which frequently have poor water solubility, biocompatibility, and brightness. In this work, we aimed to improve the water solubility as well as brightness of coumarin-based fluorophores for detecting biothiols by modifying their donor region. Our results demonstrated that 4-piperidinopiperidine as a donor improved the brightness and water solubility greatly. Next, we applied this probe in living cell imaging. We assumed that this probe could be used to detect an abnormal level of glutathione within hepatocellular carcinoma and tested this belief with human hepatocellular carcinoma, which demonstrated that this probe is a powerful chemical tool that could distinguish tumor tissues from normal tissues. To conclude, the probe we constructed has the potential to serve as a novel tool for the clinical diagnosis of hepatocellular carcinoma.

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.

Ovarian cancer is a serious threat to women's health, and its mortality rate is the highest in gynecological cancer. At present, there is a lack of effective and convenient early diagnosis techniques for ovarian cancer. Most of the patients with ovarian cancer are found in the middle and late stage, thus missing the best time for treatment. Therefore, the rapid, sensitive, economic and accurate detection of early ovarian cancer is of great significance. In recent years, lysophosphatidic acid (LPA) has been found to increase in serum in the early stage of ovarian cancer, but less in other diseases. Therefore, LPA is a promising and highly specific marker of ovarian cancer. To detect LPA, many detection techniques have been developed, and great progress has been made in this field. This paper summarizes the detection methods of LPA, and focuses on the important progress in this field in recent years. Finally, the challenges and prospects of LPA marker detection in real clinical application are also prospected.

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...

PURPOSE Somatic mutations derived from the expansion of clonal populations of blood cells (clonal hematopoiesis of indeterminate potential, or CHIP) may be detected in sequencing of cell-free DNA (cfDNA) samples. We evaluated the potential implications of CHIP in targeted sequencing of plasma samples using matched peripheral blood mononuclear cells (PBMCs) from patients with lung cancer to identify potential CHIP-associated mutations. MATERIALS AND METHODS A total of 332 plasma and corresponding PBMC samples were collected predose, cycle 1 day 1 (C1D1), from the randomized, phase III study (OAK) comparing atezolizumab versus docetaxel in previously treated patients with non–small-cell lung cancer (NSCLC). The samples were analyzed with the AVENIO ctDNA Surveillance Kit (for research use only; not for use in diagnostic procedures), a 198-kb next-generation sequencing panel targeting cancer-related genes. CHIP variants were assessed by analyzing both plasma and PBMC sequencing data. RESULTS A range of zero to eight CHIP variants (median = one) was detected per cfDNA sample. Most of these variants were not in the Database of Single Nucleotide Polymorphisms (dbSNP). The number of CHIP variants was positively associated with age, and TP53 was the most frequently mutated gene. Furthermore, the allele frequency was less variable over time for CHIP variants than for tumor-derived variants. CONCLUSION CHIP-derived mutations are present in late-stage NSCLC. However, not all plasma samples had CHIP mutations detected with targeted panel sequencing. Paired PBMC sequencing analysis may be needed to remove CHIP variants for comprehensive genomic profiling using plasma samples to identify true somatic mutations.

Background Blunted reward processing has emerged as an endophenotype of major depressive disorder (MDD), but mechanistic understanding for this deficit remains elusive. The current event-related potential study examined whether this aberration is driven by the blunted effect of perceived control on reward processing. Methods We adapted a well-validated gambling task in which perceived control was exercised by choice in 29 individuals with current MDD and 31 healthy controls. We examined the reward positivity in response to personally chosen versus passively received rewards. Results We found that MDD patients relative to healthy controls exhibited a blunted reward positivity when rewards were delivered following voluntary choices but not when they were delivered following passive choices. This pattern was not observed during the relatively late stage, as indexed by the P300, of feedback processing. Limitation The current findings may be confounded with medication and anxiety. Conclusions These findings suggest that deficient reward processing in MDD is attributable to the deficiency in boosting reward responsivity by perceived control exercised by choice.

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.

A synthetic strategy to provide two late-stage intermediates for the synthesis of diverse analogues of ROMK inhibitors for the treatment of hypertension and heart failure is described. Key transfor...

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.

Parkinson’s disease (PD) is a common neurodegenerative disorder, with a continuously increasing prevalence. With improved clinical and therapeutic management of PD, more patients reach later stages of the disease, meaning they may face new clinical problems that were not commonly approached. This gave way to the description of a new PD stage, late-stage PD (LSPD), which is clinically discernible from the advanced-stage one. Therefore, LSPD patients have new and different needs, regarding pharmacological and non pharmacological interventions, including palliative care and multidisciplinary teams. LSPD patients constitute an‘orphan population’, who traditionally was excluded from previous studies, due to its high disability. With this manuscript, we intend to review specific management challenges of LSPD patients, covering this new concept and its clinical features, how to assess these patients, therapeutic recommendations, as well as discussing ongoing research and future perspectives.

The perspective of people with dementia, particularly late-stage dementia, is often excluded from research, even from methods like Participatory Action Research (PAR), which aim to democratise rese...

SummaryThe combination of Cytotoxic T-Lymphozyte Antigen-4 (CTLA‑4) and Programmed death-1 (PD‑1) antibodies and the combination of BRAF and MEK inhibitors are the current clinical standards for combination immune and targeted therapy for melanoma, respectively. The success of these therapies has stimulated research into novel drug combinations for melanoma, of which a large majority are based on combination with PD‑1 or PD-Ligand 1 (PD-L1) blocking drugs. Thus, the aim is to provide an overview of the most important combination strategies in late stage clinical development and an outlook on drug combinations in early development that might enter larger clinical trials within the next few years.

Colorectal cancer is one of the most significant types of cancer, ranking second in the world’s mortality cases. As colorectal cancer is often diagnosed at a late stage of disease progression, effe...

Purpose of review Pancreatic cancer is the third leading cause of cancer death and with a dismal 5-year survival of 10%. Poor survival of pancreatic cancer is mostly due to its presentation and diagnosis at a late stage. The present article aims to update clinicians with recent progress in the field of early detection of pancreatic cancer. Recent findings Pancreatic cancer screening is not recommended in the general population due to its low prevalence. In this review, we discuss high-risk groups for pancreatic cancer, including inherited predisposition to pancreatic cancer, new-onset diabetes, mucinous pancreatic cyst, and chronic pancreatitis. We discuss methods of enrichment of high-risk groups with clinical models using electronic health records and biomarkers. We also discuss improvements in imaging modalities and emerging role of machine learning and artificial intelligence in the field of imaging and biomarker to aid in early identification of pancreatic cancer. Summary There are still vast challenges in the field of early detection of pancreatic cancer. We need to develop noninvasive prediagnostic validated biomarkers for longitudinal surveillance of high-risk individuals and imaging modalities that can identify pancreatic cancer early.

Aims Though the pathogenesis of Legg-Calve-Perthes disease (LCPD) is unknown, repetitive microtrauma resulting in deformity has been postulated. The purpose of this study is to trial a novel upright MRI scanner, to determine whether any deformation occurs in femoral heads affected by LCPD with weightbearing. Methods Children affected by LCPD were recruited for analysis. Children received both standing weightbearing and supine scans in the MROpen upright MRI scanner, for coronal T1 GFE sequences, both hips in field of view. Parameters of femoral head height, width, and lateral extrusion of affected and unaffected hips were assessed by two independent raters, repeated at a one month interval. Inter- and intraclass correlation coefficients were determined. Standing and supine measurements were compared for each femoral head. Results Following rigorous protocol development in healthy age-matched volunteers, successful scanning was performed in 11 LCPD-affected hips in nine children, with seven unaffected hips therefore available for comparison. Five hips were in early stage (1 and 2) and six were in late stage (3 and 4). The mean age was 5.3 years. All hips in early-stage LCPD demonstrated dynamic deformity on weightbearing. Femoral head height decreased (mean 1.2 mm, 12.4% decrease), width increased (mean 2.5 mm, 7.2% increase), and lateral extrusion increased (median 2.5 mm, 23% increase) on standing weightbearing MRI compared to supine scans. Negligible deformation was observed in contra-lateral unaffected hips, with less deformation observed in late-stage hips. Inter- and intraclass reliability for all measured parameters was good to excellent. Conclusion This pilot study has described an effective novel research investigation for children with LCPD. Femoral heads in early-stage LCPD demonstrated dynamic deformity on weightbearing not previously seen, while unaffected hips did not. Expansion of this protocol will allow further translational study into the effects of loading hips with LCPD. Cite this article: Bone Joint Open 2020;1-7:364–369.

Background and aims Double-guidewire technique (DWT) has been successfully performed by experts in difficult biliary cannulation as an advanced technique. This study aimed to define the learning curve and safety of DWT by trainees during hands-on endoscopic retrograde cholangiopancreatography (ERCP) training. Methods Patients were eligible for inclusion in the study if the biliary cannulation was difficult and the pancreatic duct was inadvertently cannulated. DWT was performed by two trainees randomly under trainers' guidance. The primary outcome was the success rate of DWT biliary cannulation of trainees. Cumulative sum analysis was used to generate visual learning curves. Results A total of 60 patients with difficult cannulation were enrolled. The main indications for ERCP were common bile duct stones (65%) and biliary stricture (31.7%). The learning curve analysis showed that to achieve a 70% rate of successful DWT, 12 procedures were needed for trainee A and 15 for trainee B. Higher targeted success rate of DWT could be achieved if the number of DWT procedures increased. Compared with the early stage of learning DWT (case 1 to 15 for each trainee), trainees had significantly higher DWT success rate in the late stage (36.7% [11/30] vs 80% [24/30], P = 0.001). The final success rate of cannulation was 98.3% (59/60). The overall rate of post-ERCP pancreatitis and adverse events was 6.7% (4/60) and 8.3% (5/60), respectively. Conclusions Double-guidewire technique was safely performed by two novel trainees during hands-on ERCP training. Fifteen procedures may be enough for trainees to achieve the competency of performing DWT. (Clinicaltrials.gov number: NCT03707613).

The current tuberculosis (TB) predicament poses numerous challenges and therefore every incremental scientific work and all positive socio-political engagements, are steps taken in the right direction to eradicate TB. Progression of the late stage TB-drug pipeline into the clinics is an immediate deliverable of this global effort. At the same time, fueling basic research and pursuing early discovery work must be sustained to maintain a healthy TB-drug pipeline. This review encompasses a broad analysis of chemotherapeutic strategies that target the DNA replication, protein synthesis, cell wall biosynthesis, energy metabolism and proteolysis of Mycobacterium tuberculosis (Mtb). It includes a status check of the current TB-drug pipeline with a focus on the associated biology, emerging targets, and their promising chemical inhibitors. Potential synergies and/or gaps within or across different chemotherapeutic strategies are systematically reviewed as well.

Objective: Brain-computer interface (BCI) based communication remains a challenge for people with later-stage amyotrophic lateral sclerosis (ALS) who lose all voluntary muscle control. Although recent studies have demonstrated the feasibility of functional near-infrared spectroscopy (fNIRS) to successfully control BCIs primarily for healthy cohorts, these systems are yet inefficient for people with severe motor disabilities like ALS. In this study, we developed a new fNIRS-based BCI system in concert with a single-trial Visuo-Mental (VM) paradigm to investigate the feasibility of enhanced communication for ALS patients, particularly those in the later stages of the disease. Methods: In the first part of the study, we recorded data from six ALS patients using our proposed protocol (fNIRS-VM) and compared the results with the conventional electroencephalography (EEG)-based multi-trial P3Speller (P3S). In the second part, we recorded longitudinal data from one patient in the late locked-in state (LIS) who had fully lost eye-gaze control. Using statistical parametric mapping (SPM) and correlation analysis, the optimal channels and hemodynamic features were selected and used in linear discriminant analysis (LDA). Results: Over all the subjects, we obtained an average accuracy of 81.3%±5.7% within comparatively short times (< 4 sec) in the fNIRS-VM protocol relative to an average accuracy of 74.0%±8.9% in the P3S, though not competitive in patients with no substantial visual problems. Our longitudinal analysis showed substantially superior accuracy using the proposed fNIRS-VM protocol (73.2%±2.0%) over the P3S (61.8%±1.5%). Significance: Our findings indicate the potential efficacy of our proposed system for communication and control for late-stage ALS patients.

To evaluate the health-related quality of life (HRQoL) of knee osteoarthritis (KOA) patients in China, compare their HRQoL with norm population, and examine the associations between the potential influencing factors and HRQoL. A cross-sectional study was conducted in 912 KOA patients from 4 provinces between March and November 2017. All participants were diagnosed according to the National Institute for Health and Care Excellence (NICE)’s criterion or the Chinese Medical Association (CMA)’s criterion. Recruited patients were surveyed for HRQoL using the 12-item Short Form (SF-12) and sociodemographic, disease-related factors. We assessed the associations between potential influencing factors and HRQoL using multiple linear regression models. Among the KOA patients, the mean physical component summary (PCS) of HRQoL was 40.91 ± 11.62, lower than norm (P

Introduction: The incidence rate of chronic kidney failure in Indonesia in 2013 was 2.0% per mil and in 2018 it increased to 3.8% per mil. Objective: The purpose of this study is to analyze the determinants of rejection of hemodialysis in Chronic Kidney Failure patients. Method: This research is a quantitative study with cross sectional approach. The population in the study were all kidney failure patients in August, amounting to 149 people. Sampling with total sampling in accordance with inclusion criteria, there were 10 patients who refused hemodialysis. Results: The results of a study with 10 patients who refused hemodialysis, 6 people (60%) covered by insurance, 5 people (50%) had kidney failure due to diabetes mellitus, 6 people (60%) patients who refused hemodialysis had poor drinking patterns, 6 people (60%) patients who reject hemodialysis have bad psychological conditions, 5 people (50%) patients who reject hemodialysis have poor family support and 6 people (60%) have poor health service support. Conclusion: The majority of hemodialysis rejection in patients with chronic kidney failure is influenced by drinking patterns, psychological conditions, family support, and poor health service support. This can be a consideration of nurses and other health teams in preparing patients and their families to make decisions according to conditions or needs of patients with chronic kidney failure. Health services can provide counseling services related to the importance of dialysis for patients with late stage chronic kidney failure, so patients choose dialysis therapy as kidney replacement therapy.

While the presence of cognitive biases among body dissatisfied individuals is supported by the literature, the nuances of these biases have yet to be fully explored. The current study examined attentional processing of body-related stimuli as a function of body dissatisfaction using eye-tracking methodology and a modified spatial cueing paradigm to evaluate early and late stage processing patterns. Undergraduate women (N = 197) completed a decision-making task involving thin, fat, and control body images while eye gaze was recorded. Reaction time analysis did not reveal a relationship between body dissatisfaction and disengagement difficulty from thin or fat body images when compared to control body images. However, analysis of eye gaze patterns revealed a relationship between body dissatisfaction and difficulty shifting visual attention away from thin body images. The findings provide partial support for an attentional bias for thin body images in body dissatisfied individuals. Moreover, the results provide further evidence for eye-tracking methodology as a more sensitive measure of cognitive biases than reaction time. Further examination of the relationship between cognitive biases and body dissatisfaction remains an important area of study as both are risk factors for eating disorders and can inform treatment interventions.