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Major changes in intra- and extracellular pH homoeostasis are shared features of most solid tumours. These changes stem in large part from the metabolic shift of most cancer cells towards glycolytic metabolism and other processes associated with net acid production. In combination with oncogenic signalling and impact from factors in the tumour microenvironment, this upregulates acid-extruding plasma membrane transport proteins which maintain intracellular pH normal or even more alkaline compared with that of normal cells, while in turn acidifying the external microenvironment. Mounting evidence strongly indicates that this contributes significantly to cancer development by favouring e.g. cancer cell migration, invasion and chemotherapy resistance. Finally, while still under-explored, it seems likely that non-cancer cells in the tumour microenvironment also exhibit altered pH regulation and that this may contribute to their malignant properties. Thus, the physical tumour microenvironment and the cancer and stromal cells within it undergo important reciprocal interactions which modulate the tumour pH profile, in turn severely impacting on the course of cancer progression. Here, we summarize recent knowledge of tumour metabolism and the tumour microenvironment, placing it in the context of tumour pH regulation, and discuss how interfering with these properties may be exploited clinically.

Viscous effects on an ideal gas flow in a supersonic convergent–divergent nozzle are a well-studied subject in classical gas dynamics. However, the ideal assumption fails on fluids that exhibit complex behaviours such as near-critical-region and non-ideal dense vapours. Under those conditions, a realistic equation of state (EOS) plays a vital role for a precise and realistic computation. This work examines the problem for solving the quasi-one-dimensional viscous compressible flow using a realistic EOS. The governing equations are discretised and solved using the fourth-order Runge–Kutta method coupled with a state-of-the-art EOS to calculate the thermodynamic properties. The role of the Grüneisen parameter along with viscous and real gas effects and their influence on the sonic point formation are discussed. The study shows that the flow may not achieve the supersonic regime for any pressure ratio depending on the combination of that parameter and the normalised friction factor. In addition, the analysis yields the discharge coefficient and the isentropic nozzle efficiency, which may achieve maximum values as a function of the stagnation conditions. Finally, the study also evaluates the formation and intensity of normal shock waves by using the Rankine–Hugoniot relations, which now depend on the real gas and viscous effects in opposition to the inviscid solution. Moreover, the methodology used captures the sonic point and shock wave position by a space marching algorithm using the Brent method for scalar minimisation. Experimental data available in the open literature corroborate the approach.

Bladder cancer associated protein (Blcap) expression is commonly down-regulated in invasive bladder cancer, and may have prognostic value given that its expression is negatively correlated with patient survival. We have previously investigated the expression patterns and cellular localization of Blcap in bladder cancer, where we found that about 20% of the lesions examined displayed strong nuclear expression of Blcap, and that this phenotype was associated with overall poor disease outcome. Here we report on the analysis of possible functional associations between nuclear expression of Blcap and canonical signaling pathways. We performed serial immunohistochemistry (IHC) analysis of bladder tissue samples, with serial sections stained with phospho-specific antibodies recognizing key signaling intermediates, such as P-Stat3, P-Akt, and P-Erk1/2, among others, in an immunophenotyping approach we have established and reported previously. Using this approach, we found that nuclear localization of Blcap was associated with expression of P-Stat3. A parallel analysis, cytokine profiling of bladder tumor interstitial fluids of samples expressing (or not) Blcap, showed interleukin (IL)-6, IL-8, and monocyte chemotactic protein 1 (MCP-1) to be correlated with nuclear expression of Blcap, independently supporting a role for Stat3 signaling in localization of Blcap. Multiple indirect immunofluorescence analysis of tissue biopsies confirmed that Blcap co-localized with Stat3. Furthermore, we could also demonstrate, using an in situ proximity ligation assay that Blcap and Stat3 are in close physical proximity of each other in bladder tissue, and that Blcap physically interacts with Stat3 as determined by co-immunoprecipitation of these proteins. Our data indicates that Blcap is a novel Stat3 interaction partner and suggests a role for Blcap in the Stat3-mediated progression of precancerous lesions to invasive tumors of the bladder.

Apocrine carcinoma of the breast is a distinctive malignancy with unique morphological and molecular features, generally characterized by being negative for estrogen and progesterone receptors, and thus not electable for endocrine therapy. Despite the fact that they are morphologically distinct from other breast lesions, no standard molecular criteria are currently available for their diagnosis. Using gel-based proteomics in combination with mass spectrometry and immunohistochemistry we have identified two novel markers, HMGCS2 and FABP7 that categorize the entire breast apocrine differentiation spectrum from benign metaplasia and cysts to invasive stages. Expression of HMGCS2 and FABP7 is strongly associated with apocrine differentiation; their expression is retained by most invasive apocrine carcinomas (IAC) showing positive immunoreactivity in 100% and 78% of apocrine carcinomas, respectively, as compared to non-apocrine tumors (16.7% and 6.8%). The nuclear localization of FABP7 in tumor cells was shown to be associated with more aggressive stages of apocrine carcinomas. In addition, when added to the panel of apocrine biomarkers previously reported by our group: 15-PGDH, HMGCR and ACSM1, together they provide a signature that may represent a golden molecular standard for defining the apocrine phenotype in the breast. Moreover, we show that combining HMGCS2 to the steroidal profile (HMGCS2+/Androgen Receptor (AR)+/Estrogen Receptor(ER)-/Progesteron Receptor (PR)- identifies IACs with a greater sensitivity (79%) as compared with the steroidal profile (AR+/ER-/PR-) alone (54%). We have also presented a detailed immunohistochemical analysis of breast apocrine lesions with a panel of antibodies against proteins which correspond to 10 genes selected from published transcriptomic signatures that currently characterize molecular apocrine subtype and shown that except for melanophilin that is overexpressed in benign apocrine lesions, these proteins were not specific for morphological apocrine differentiation in breast.

Sporotrichosis is a fungal infection of man and animals caused by Sporothrix complex. It usually presents as a lymphocutaneous form, but disseminated disease may occur. Given the paucity of data about HIV/AIDS and sporotrichosis co-infection, a systematic review of reported cases of HIV-associated sporotrichosis found via Pubmed (1984–2013) was done. A total of 39 papers were included, and 58 patients’ data analyzed. Thirty-three (56.9 %) cases were from Brazil and 18 (31 %) from the USA. Patients’ mean age was 37.8 ± 10.4 years; males predominated (84.5 %). The median CD4 + cell count was 97 cells/mm 3 . The most common clinical forms were disseminated and disseminated cutaneous with 33 (56.9 %) and 10 (17.5 %) patients, respectively. There was a correlation between CD4 + count and clinical categories ( p  = 0.002). Mortality was 30 % and there was a correlation between central nervous system involvement and death ( p  < 0.001).

The purpose of this study was to evaluate the bioactive compounds and antioxidant activity of extracts from araçá (Psidium cattleianum), butiá (Butia eriospatha), and pitanga (Eugenia uniflora) fruits with different flesh colors (i.e., purple, red, and orange), and blackberries (Rubus sp.; cv. Xavante and Cherokee) collected in the southern region of Brazil. The content of ascorbic acid, total carotenoids, and phenolics were determined. The profile of the phenolic compounds was assessed by high-performance liquid chromatography combined with diode array detection (HPLC-DAD). The antioxidant activity was determined using the ferric-reducing antioxidant power (FRAP) assay, 2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH) assay, total reactive antioxidant potential (TRAP) assay, and total antioxidant reactivity (TAR) assay. The Xavante blackberry and purple-fleshed pitanga showed the highest total phenolic content [816.50 mg gallic acid equivalents (GAE)/100g and 799.80 mg GAE/100g, respectively]. The araçá and red-fleshed pitanga showed the highest carotenoid content (6.27 ug β-carotene/g and 5.86 ug β-carotene/g, respectively). The fruits contained several phenolic compounds such as quercetin derivatives, quercitrin, isoquercitrin, and cyanidin derivatives, which may contribute differentially to the antioxidant capacity. The highest scavenging activity in the DPPH assay was found for purple-fleshed pitanga (IC50 36.78 mg/L), blackberries [IC50 44.70 (Xavante) and IC50 78.25 mg/L (Cherokee)], and araçá (IC50 48.05 mg/L), which also showed the highest FRAP, followed by orange- and red-fleshed pitanga. Our results revealed that some fruits grown in southern Brazil such as purple-fleshed pitanga, blackberries, and araçá are rich sources of phenolic compounds and have great antioxidant activity.

Chikungunya (CHIKV) is a reemerging arboviral disease and represents a global health threat because of the unprecedented magnitude of its spread. Diagnostics strategies rely heavily on reverse transcriptase-polymerase chain reaction (RT-PCR) and antibody detection by enzyme-linked Immunosorbent assay (ELISA). Rapid diagnostic tests (RDTs) are available and promise to decentralize testing and increase availability at lower healthcare system levels. We aim to identify the extent of research on CHIKV RDTs, map the global availability of CHIKV RDTs, and evaluate the accuracy of CHIKV RDTs for the diagnosis of CHIKV. We included studies reporting symptomatic individuals suspected of CHIKV, tested with CHIKV RDTs, against the comparator being a validated laboratory-based RT-PCR or ELISA assay. The primary outcome was the accuracy of the CHIKV RDT when compared with reference assays. Medline, EMBASE, and Scopus were searched from inception to 13 October 2021. National regulatory agencies (European Medicines Agency, US Food and Drug Administration, and the Brazilian National Health Surveillance Agency) were also searched for registered CHIKV RDTs. Seventeen studies were included and corresponded to 3,222 samples tested with RDTs between 2005 and 2018. The most development stage of CHIKV RDTs studies was Phase I (7/17 studies) and II (7/17 studies). No studies were in Phase IV. The countries that manufacturer the most CHIKV RDTs were Brazil (n = 17), followed by the United States of America (n = 7), and India (n = 6). Neither at EMA nor FDA-registered products were found. Conversely, the ANVISA has approved 23 CHIKV RDTs. Antibody RDTs (n = 43) predominated and demonstrated sensitivity between 20% and 100%. The sensitivity of the antigen RDTs ranged from 33.3% to 100%. The landscape of CHIKV RDTs is fragmented and needs coordinated efforts to ensure that patients in CHIKV-endemic areas have access to appropriate RDTs. Further research is crucial to determine the impact of such tests on integrated fever case management and prescription practices for acute febrile patients.

Food ingestion is one of the defining behaviours of all animals, but its quantification and analysis remain challenging. This is especially the case for feeding behaviour in small, genetically tractable animals such as Drosophila melanogaster . Here, we present a method based on capacitive measurements, which allows the detailed, automated and high-throughput quantification of feeding behaviour. Using this method, we were able to measure the volume ingested in single sips of an individual, and monitor the absorption of food with high temporal resolution. We demonstrate that flies ingest food by rhythmically extending their proboscis with a frequency that is not modulated by the internal state of the animal. Instead, hunger and satiety homeostatically modulate the microstructure of feeding. These results highlight similarities of food intake regulation between insects, rodents, and humans, pointing to a common strategy in how the nervous systems of different animals control food intake. Feeding is an important behaviour, but its quantification remains challenging, particularly in small animal models like Drosophila melanogaster . Here the authors describe a method which uses capacitive sensing for automated high-resolution measuring of feeding behaviour in individual flies.

Changes in postural control associated with clinical practice or specific conditions such as the presence of neck pain remain unexplored in dental students. Therefore, this study aimed to explore the time-course changes in postural control complexity among dental students enrolled in clinical practice, comparing those with and without neck pain. We used an online Nordic Musculoskeletal Questionnaire for group allocation and center of pressure (CoP) oscillations with a tri-axial Bertec force plate. Baseline data were acquired from dental students with neck pain (NP) ( n  = 21) and asymptomatic in a control group ( n  = 23), before starting their clinical practice, and assessments were repeated after their first semester. CoP fluctuations were determined through the calculation of sample entropy. Both groups had similar postural control at baseline, but asymptomatic students exhibited more irregular CoP AP ( p  = 0.013) and ML ( p  = 0.015) oscillations, while students with neck pain showed a more rigid pattern ( p  = 0.004) in the AP direction at the endpoint. Our results showed that dental students’ postural control complexity decreased during the first semester of clinical practice. Over time, asymptomatic students exhibited more random postural control patterns, while students with neck pain demonstrated more rigid postural control during upright stance, indicating that postural control complexity differs between students with and without neck pain when exposed to clinical training.