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Even though the impact of the position of response options on answers to multiple-choice items has been investigated for decades, it remains debated. Research on this topic is inconclusive, perhaps because too few studies have obtained experimental data from large-sized samples in a real-world context and have manipulated the position of both correct response and distractors. Since multiple-choice tests' outcomes can be strikingly consequential and option position effects constitute a potential source of measurement error, these effects should be clarified. In this study, two experiments in which the position of correct response and distractors was carefully manipulated were performed within a Chilean national high-stakes standardized test, responded by 195,715 examinees. Results show small but clear and systematic effects of options position on examinees' responses in both experiments. They consistently indicate that a five-option item is slightly easier when the correct response is in A rather than E and when the most attractive distractor is after and far away from the correct response. They clarify and extend previous findings, showing that the appeal of all options is influenced by position. The existence and nature of a potential interference phenomenon between the options' processing are discussed, and implications for test development are considered.

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Background: The purpose of this study was to understand the experiences of Black patients with cancer in health care by comparing drivers of high and low ratings. Methods: Semistructured in‐depth interviews were conducted with 18 Black patients with cancer recruited from cancer survivorship support groups and Facebook between May 2019 and March 2020. Interviews were coded across all transcripts by using a thematic analysis approach before comparing low‐ and high‐rating groups. Results: There were three major themes that influenced whether patients rated their care as low or high, which included the patient–provider relationship, health care staff interactions, and cancer care coordination. For example, the high‐rating group described good communication with the health care team as physicians listening to their needs, being responsive to their concerns, and providing recommendations on how to address side effects. In contrast, the low‐rating group described poor communication with their health care team as their needs being dismissed and being excluded from decision‐making processes. Additionally, there were two distinct themes that influenced patients' low ratings: insurance and financial toxicity issues and experiences of health care discrimination. Conclusions: In an effort to promote equitable cancer care experiences for Black patients, it is important that health systems work to prioritize patient interactions with health care providers and staff, comprehensive care management for patients with cancer, and reductions in the financial burden of caring for cancer. In this qualitative analysis, three factors were found that influenced both low ratings and high ratings, but there were two distinct factors that influenced low ratings. This study lays out various ways health care teams may improve patient care experiences for Black patients with cancer and positively affect health care outcomes. [ABSTRACT FROM AUTHOR]

Evidence suggests children HIV‐exposed and uninfected (CHEU) experience poor growth. We analysed child anthropometrics and explored factors associated with stunting among Malawian CHEU. Mothers with HIV and their infants HIV‐exposed were enroled in a nationally representative prospective cohort within the National Evaluation of Malawi's Prevention of Mother‐to‐Child HIV Transmission Programme after Option B+ implementation (2014–2018). Anthropometry was measured at enrolment (age 1–6 months), visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight‐for‐age (WAZ) and length‐for‐age (LAZ) z‐scores were calculated using World Health Organization Growth Standards; underweight and stunting were defined as WAZ and LAZ more than 2 standard deviations below the reference median. Multivariable logistic regression restricted to CHEU aged 24 months (±3 months) was used to identify factors associated with stunting. Among 1211 CHEU, 562/1211 attended visit 2, of which 529 were aged 24 months (±3 months) and were included. At age 24 months, 40.4% of CHEU were stunted and/or underweight, respectively. In multi‐variable analysis, adjusting for child age and sex, the odds of stunting were higher among CHEU with infectious disease diagnosis compared to those with no diagnosis (adjusted odds ratio = 3.35 [95% confidence interval: 1.82–6.17]), which was modified by co‐trimoxazole prophylaxis (p = 0.028). Infant low birthweight was associated with an increased odds of stunting; optimal feeding and maternal employment were correlated with reduced odds. This is one of the first studies examining CHEU growth since Option B+. Interventions to improve linear growth among CHEU should address their multi‐faceted health risks, alongside maternal ART prescription, and follow‐up of mother‐child pairs. Key messages: Understanding the health risks of children HIV‐exposed and uninfected (CHEU) and the impact on their growth is of paramount importance for optimizing their health.This is one of the first studies examining correlates of CHEU growth since the implementation of Option B+ and uses a random subsample of a nationally representative cohort of women with HIV and CHEU in Malawi.Factors associated with stunting included infant low birthweight, optimal feeding, co‐trimoxazole prophylaxis, and maternal employment.Interventions targeting modifiable risk factors, alongside maternal antiretroviral therapy, and improved nutritional follow‐up of CHEU will contribute to improving CHEU growth in Malawi. [ABSTRACT FROM AUTHOR]

Objectives: The authors aim to evaluate the "point-of-care" transfontanellar ultrasound (TU) as an extension to pediatric physical examination and suggest a TU teaching protocol. Methods: The students were randomly divided into two groups, group A (12 participants) and group B (15 participants). The first group only received theoretical training, while the second group received theoretical and practical training. A third group, group C, included 15 pediatricians and interns who also received theoretical and practical training. All the participants underwent multiple-choice testing before and after a four-hour short course on TU. Six months later, another evaluation was performed to analyze the retained knowledge. Furthermore, a questionnaire based on the Likert scale was administered to evaluate satisfaction. Results: The cognitive evaluation (maximum score = 10 points) before and after training increased in group A from 4,0 ± 1,04 to 7,5 ± 1,2 (p < 0.001) and, 6 months later, to 6,5 ± 1,16 (p < 0.003); in group B from 3,8 ± 1,24 to 8,8 ± 1,01 (p < 0.001) and, 6 months later, to 8,46 ± 0,91 (p < 0.001); and in group C from 6,0 ± 0,75 to 9,0 ± 0,75 (p < 0.001) and, 6 months later, to 8,8 ± 0,77 (p < 0.001). The average satisfaction estimated by the Likert scale was over 80% for all questions. Conclusion: Cognitive assessment before and after classes and training reveals progress in learning, with knowledge retention in 6 months. Theoretical-practical courses are well accepted. [ABSTRACT FROM AUTHOR]

Widespread use of antiretroviral drugs for pregnant/breastfeeding females with human immunodeficiency virus (HIV) has led to declining vertical transmission. Despite being HIV-uninfected, the increasing number of children who are HIV-exposed and uninfected (CHEU) often present with developmental alterations. We review seminal and recent evidence on the neurological development of CHEU and associations with early life HIV/antiretroviral exposure. Our conceptual model highlights the numerous exposures and universal risk factors for CHEU developmental disorders. Early studies suggest a significant association between HIV exposure and neurological abnormalities, varying according to the burden of HIV-specific exposures and other risk factors. More recent observations from the modern era are inconsistent, although some studies suggest specific antiretrovirals may adversely affect neurological development of CHEU. As the CHEU population continues to grow, alongside simultaneous increases in types and combinations of antiretrovirals used in pregnancy, long-term monitoring of CHEU is necessary for understanding the effects of HIV/antiretroviral exposure on CHEU developmental outcomes. What this paper adds Evidence on the neurological development of children who are human immunodeficiency virus (HIV)-exposed and uninfected (CHEU) is synthesized. Comparisons are made to children who are HIV-unexposed, across treatment eras and settings, and by antiretroviral drug regimens and drug classes. CHEU exposures are complex and include HIV-specific and universal risk factors which may affect development during the early years of life. [ABSTRACT FROM AUTHOR]

Anamnesis: A 5-year-old mixed breed entire bitch was presented with bloody vaginal discharge and abdominal distension. Clinical and laboratory findings: Physical examination and abdominal ultrasonography suggested the presence of a left ovarian tumor. At histopathological examination it was diagnosed as granulosa cell tumor. Treatment approach: An exploratory laparotomy was performed followed by ovariohysterectomy to remove the intra-abdominal mass. Conclusion: The clinical, ultrasonographic and histologic signs in this case support other literature reports. Ultrasonography, in combination with histopathologic analysis is a fundamental tool for detection of ovarian tumors, especially tumors of the granulosa cells. [ABSTRACT FROM AUTHOR]

This paper brings advances in weather data collection and modeling, and developments in socioeconomic climate microsimulations to bear on the analysis of the implications of climate change (CC) in the design of public policies to combat food insecurity. It uses new downscaled predictions of future climate in 2050, derived from three Earth System Models calibrated with a new historical weather station dataset for Peru. This climate data is used in a three-stage socioeconomic microsimulation model that includes climate risk, and deals with the endogeneity of incomes and simultaneity of expected food consumption and its variability. We estimate the impact of CC on agricultural yields, and find results consistent and fully bounded within what the global simulations literature has found, with yields falling up to 13% in some regions. However, we show that these drops (and increases) in yields translate to much smaller changes in food consumption, and also surprisingly, to very minor impacts on vulnerability to food insecurity. The document explores what explains this surprising result, showing that in addition to characteristics that are specific to Peru, there are household and market mediating mechanisms that are available in all countries, which explain how changes in yields, and corresponding farm incomes have a reduced impact in vulnerability to food insecurity. Finally, in light of these findings, we explore which policies might have greater impact in reducing food insecurity in contexts of hunger prevalence. [ABSTRACT FROM AUTHOR]

Background: Fibrosis is present in several pathologies associated with mammary carcinogenesis. Objective: To evaluate and quantify the fibrosis present in malignant and benign mammary neoplasms in bitches. Methods: Eighty-three samples were divided according to histopathological diagnosis into benign (n= 21) and malignant (n= 62) neoplasms. Haematoxylin-eosin and Masson's trichrome were used to locate the connective tissue, and the extent of fibrosis was assessed with image software. Results: Benign neoplasms were classified into adenomas (cystic, complex, and tubular), benign mixed tumor, and ductal and lobular hyperplasia. Malignant neoplasms were classified as carcinomas (complex, mixed tumor, in situ tubular, tubulopapillary, and solid). Grade I was the most prevalent histopathological class, followed by grade II and III. Fibrosis was classified as severe, moderate, or discrete. No significant (p>0.05) difference was observed for the percentage of fibrosis between malignant and benign group neoplasms. However, difference (p=0.028) was found for fibrosis percentage between histopathological subtypes of tumors. The benign subtype of lobular hyperplasia presented differences between cystic adenoma and benign mixed tumor. The in situ malignant tubular carcinoma subtype presented differences between solid and tubulopapillary carcinoma. Conclusions: Fibrosis in canine mammary tumors can be estimated with Massons's trichrome staining. [ABSTRACT FROM AUTHOR]

Abstract: Adaptive evolution in response to one selective challenge may disrupt other important aspects of performance. Such evolutionary trade‐offs are predicted to arise in the process of local adaptation, but it is unclear if these phenotypic compromises result from the antagonistic effects of simple amino acid substitutions. We tested for trade‐offs associated with beneficial mutations that confer tetrodotoxin (TTX) resistance in the voltage‐gated sodium channel (NaV1.4) in skeletal muscle of the common garter snake (Thamnophis sirtalis). Separate lineages in California and the Pacific Northwest independently evolved TTX‐resistant changes to the pore of NaV1.4 as a result of arms race coevolution with toxic prey, newts of the genus Taricha. Snakes from the California lineage that were homozygous for an allele known to confer large increases in toxin resistance (NaV1.4LVNV) had significantly reduced crawl speed compared to individuals with the ancestral TTX‐sensitive channel. Heterologous expression of native snake NaV1.4 proteins demonstrated that the same NaV1.4LVNV allele confers a dramatic increase in TTX resistance and a correlated decrease in overall channel excitability. Our results suggest the same mutations that accumulate during arms race coevolution and beneficially interfere with toxin‐binding also cause changes in electrophysiological function of the channel that may affect organismal performance. This trade‐off was only evident in the predator lineage where coevolution has led to the most extreme resistance phenotype, determined by four critical amino acid substitutions. If these biophysical changes also translate to a fitness cost—for example, through the inability of T. sirtalis to quickly escape predators—then pleiotropy at this single locus could contribute to observed variation in levels of TTX resistance across the mosaic landscape of coevolution. [ABSTRACT FROM AUTHOR]

Development of cervical cancer is associated with persistent infections by high-risk human papillomavirus (HPV). Although current HPV L1-based prophylactic vaccines prevent infection, they do not help to eliminate prevalent infections or lesions. Our aims were (i) to generate a vaccine combining prophylactic and therapeutic properties by producing chimeric capsomers after fusion of the L1 protein to different fragments of E2 from HPV 16, and (ii) to evaluate their capacity to generate an antitumoral cellular response, while conserving L1 neutralizing epitopes. Chimeric proteins were produced in Escherichia coli and purified by glutathione S-transferase (GST)-affinity chromatography. Their structure was characterized using size exclusion chromatography, sucrose gradient centrifugation, electron microscopy, and anti-L1 enzyme-linked immunosorbent assay. All chimeric proteins form capsomers and heterogeneous aggregates. One, containing part of the carboxy-terminal domain of E2 and its hinge region (L1Δ+E2H/NC, aa 206-307), conserved the neutralizing epitope H16.V5. We then evaluated the capacity of this chimeric protein to induce a cytotoxic T-cell response against HPV 16 E2. In 51Cr release cytotoxicity assays, splenocytes from C57BL/6 immunized mice recognized and lysed TC-1/E2 cells, which express and present endogenously processed E2 peptides. Moreover, this E2-specific cytotoxic response inhibited the growth of tumors of TC-1/E2 cells in mice. Finally, we identified an epitope (aa 292-301) of E2 involved in this cytotoxic response. We conclude that the L1Δ+E2H/NC chimeric protein produced in bacteria can be an effective and economically interesting candidate for a combined prophylactic and therapeutic vaccine that could help eliminating HPV16-positive low-grade cervical lesions and persistent viral infections, thus preventing the development of lesions and, at the same time, the establishment of new infections. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Justicia spicigera is used for the empirical treatment of cervical cancer in Mexico. Recently, we showed that Justicia spicigera extracts exerted cytotoxic and antitumoral effects and the major component of this extract was kaempferitrin (KM). Materials and methods: The cytotoxic and apoptotic effect of KM on human cancer cells and human nontumorigenic cells were evaluated using MTT and TUNEL assays, and Annexin V/Propidium iodide detection by flow cytometry. The effect of KM on cell cycle was analyzed by flow cytometry with propidium iodide. The apoptotic and cell cycle effects were also evaluated by western blot analysis. Also, different doses of KM were injected intraperitoneally daily into athymic mice bearing tumors of HeLa cells during 32 days. The growth and weight of tumors were measured. Results: KM induces high cytotoxic effects in vitro and in vivo against HeLa cells. The general mechanisms by which KM induces cytotoxic effects include: cell cycle arrest in G1 phase and apoptosis via intrinsic pathway in a caspase dependent pathway. Also, KM exerts chemopreventive and antitumor effects. Conclusion: KM exerts cytotoxic and antitumor effects against HeLa cells. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Phoradendron serotinum is commonly used in Mexican traditional medicine for the empirical treatment of cancer. However, there are no studies regarding the antitumoral or immunomodulatory activities of Phoradendron serotinum. Materials and methods: The in vivo toxicity of ethanolic extracts of Phoradendron serotinum (PSE) was evaluated in mice according to the Lorke procedure. The in vitro immunomodulatory effects of PSE were evaluated estimating the effects of PSE on the pinocytosis, NO production and lysosomal enzyme activity in murine macrophages RAW 264.7. The effects of PSE on the proliferation of murine splenocytes and NK cell activity were also assayed. The cytotoxic effects on TC-1 (lung murine cancer cells) were evaluated using the MTT assay, whereas the apoptotic effect of PSE on TC-1 cells was evaluated using TUNEL assay. Also, different doses of PSE were injected intraperitoneally daily into C57BL/6 mice bearing tumors of TC-1 cells during 25 days. The growth and weight of tumors was measured. In addition, the levels of IL-2, IL-6, IL-12, IL-23 and IFN-γ in murine serum and supernatants of K562 cell—murine splenocyte cocultures were measured. Results: PSE stimulated the proliferation, pinocytosis and lysosomal enzyme activity in murine macrophages with a similar potency than lypopolisaccharides 1μg/ml. In addition, PSE stimulated the proliferation of murine splenocytes and induced the NK cell activity. PSE showed cytotoxic (IC50 =1.9μg/ml) and apoptotic effects against TC-1 cells. The LD50 was 125mg/kg by intraperitoneal route (i.p.) and 375mg/kg by oral route. PSE administrated at 1, 5 and 10mg/kg i.p. inhibited the tumor growth by 18%, 40% and 69%, respectively, in mice bearing TC-1 tumor. PSE increased the in vitro and in vivo release of IL-2, IL-6 and IFN-γ but lacked effect on IL-12 and IL-23 release. Conclusions: Phoradendron serotinum shows moderate toxic effects in vivo, exerts cytotoxic and apoptotic effects on TC-1 cells. Phoradendron serotinum also has antitumor effects in mice bearing TC-1 tumor and induces immunomodulatory activities in vivo. The results suggest that antitumoral effects of PSE are related with the production of immunity-related cytokines. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Medicinal plants are an important source of antitumor compounds. This study evaluated the acute toxicity in vitro and in vivo, as well as the cytotoxic, antitumor and immunomodulatory effects of ethanolic extracts of Justicia spicigera leaves (JSE). Materials and methods: The in vitro and in vivo toxicity of JSE was evaluated with comet assay in peripheral blood mononuclear cells (PBMC) and acute toxicity in mice, according to the Lorke procedure, respectively. The apoptotic effect of JSE on human cancer cells and human noncancerous cells was evaluated using flow cytometry with annexin-Alexa 488/propidium iodide. Also, different doses of JSE were injected intraperitoneally daily into athymic mice bearing tumors of HeLa cells during 18 days. The growth and weight of tumors were measured. The in vitro immunomodulatory effects of JSE were evaluated estimating the effects of JSE on the phagocytosis of the yeast Saccharomyces cerevisiae, NO production and H2O2 release in macrophages, as well as the proliferation of splenocytes and NK activity. Results: The comet assay showed that only JSE tested at 200 and 1000μg/ml induced a significantly DNA damage in PBMC, compared to untreated cells, whereas the LD50 was >5000mg/kg by intraperitoneal route (i.p.) and by oral route. JSE showed pro-apoptotic (Annexin/PI) effects by 35% against HeLa cells, but lack toxic effects against human normal cells. JSE administrated at 10, 50 and 100mg/kg i.p. inhibited the tumor growth by 28%, 41% and 53%, respectively, in mice bearing HeLa tumor. JSE stimulated, in a concentration dependent manner, the phagocytosis of Saccharomyces cerevisiae yeasts, the NO production and H2O2 release by human differentiated macrophages. In addition, JSE stimulated the proliferation of murine splenocytes and induced the NK cell activity. Conclusion: Justicia spicigera shows low toxic effects in vitro and in vivo, exerts apoptotic effects on HeLa cells, has antitumor effects in mice bearing HeLa tumor and induces immunomodulatory activities in vitro. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmagological relevance: Medicinal plants are an important source of antitumor compounds. This study evaluated the acute toxicity in mice, as well as the cytotoxic and antitumoral effects of methanolic extracts of Croton lechleri leaves (CLE). Materials and methods: The cytotoxicity of CLE on human cancer cell lines and human non-cancerous cells was evaluated using the MTT and apoptosis assays. Apoptosis induced by CLE on human cancer cell lines was determined using flow cytometry with annexin-Alexa 488/propidium iodide. The acute toxicity in mice was performed according to the Lorke procedure. Different doses of CLE were injected intraperitoneally daily into athymic mice bearing tumor during 18 days. The growth and weight of tumors was measured. Results: CLE showed low IC50 values on HeLa (17μg/ml) cells but lack toxic effects against human normal cells. Induction of cell death in HeLa cells by CLE was confirmed by an increase of apoptosis (Annexin/PI) by 30% compared to untreated cells. The LD50 was 356mg/kg by intraperitoneal route (i.p.) and 500mg/kg by oral route. CLE administrated at 1, 10 and 50mg/kg i.p. inhibited the tumor growth by 38%, 48% and 59%, respectively, in mice bearing HeLa tumor. Conclusion: Croton lechleri shows moderate toxic effects in vivo, exerts cytotoxic effects on HeLa cells and has antitumor effects in mice bearing HeLa tumor. [ABSTRACT FROM AUTHOR]