Sarcoidosis of the breast: an unusual clinical presentation

Introdução: a sarcoidose é uma doença granulomatosa sistêmica crônica de etiologia desconhecida. A mama pode ser envolvida em menos de 1% dos casos e, muitas vezes, imita os carcinomas ao exame clínico. Relato de caso: aqui, os autores relatam uma mulher de 54 anos que teve história de eritema nodoso, apresentou quadro clinico sugestivo de mastalgia, cuja mamografia e ultra-somapresentaram densidades parenquimatosas heterogêneas inespecíficas ilaterais. O estudo histopatológico revelou granulomas de células gigantes não-caseosos. Especificamente, os níveis séricos de enzima conversora de angiotensina (ECA) estavam elevados e uma TC apresentou pequenos nódulos pulmonares bilaterais distribuídos ao longo da pleura e feixes broncovasculares (padrãoperilinfático), porém sem gânglios bilaterais hilar e mediastinal. A paciente foi tratado com prednisolona e metotrexato, e atualmente está assintomática. Conclusão: o envolvimento mamário por sarcoidose, embora raro, deve ser considerado ao lidar com lesões granulomatosas da mama

Repeated Assessment of Exploration and Novelty Seeking in the Human Behavioral Pattern Monitor in Bipolar Disorder Patients and Healthy Individuals

Exploration and novelty seeking are cross-species adaptive behaviors that are dysregulated in bipolar disorder (BD) and are critical features of the illness. While these behaviors have been extensively quantified in animals, multivariate human paradigms of exploration are lacking. The human Behavioral Pattern Monitor (hBPM), a human version of the animal open field, identified a signature pattern of hyper-exploration in manic BD patients, but whether exploratory behavior changes with treatment is unknown. The objective of this study was to assess the sensitivity of the hBPM to changes in manic symptoms, a necessary step towards elucidating the neurobiology underlying BD.Twelve acutely hospitalized manic BD subjects and 21 healthy volunteers were tested in the hBPM over three sessions; all subjects were retested one week after their first session and two weeks after their second session. Motor activity, spatial and entropic (degree of unpredictability) patterns of exploration, and interactions with novel objects were quantified. Manic BD patients demonstrated greater motor activity, extensive and more unpredictable patterns of exploration, and more object interactions than healthy volunteers during all three sessions. Exploration and novelty-seeking slightly decreased in manic BD subjects over the three sessions as their symptoms responded to treatment, but never to the level of healthy volunteers. Among healthy volunteers, exploration did not significantly decrease over time, and hBPM measures were highly correlated between sessions.Manic BD patients showed a modest reduction in symptoms yet still demonstrated hyper-exploration and novelty seeking in the hBPM, suggesting that these illness features may be enduring characteristics of BD. Furthermore, behavior in the hBPM is not subject to marked habituation effects. The hBPM can be reliably used in a repeated-measures design to characterize exploration and novelty seeking and, in parallel with animal studies, can contribute to developing treatments that target neuropsychiatric disease

Photo-Detectors for Time of Flight Positron Emission Tomography (ToF-PET)

We present the most recent advances in photo-detector design employed in time of flight positron emission tomography (ToF-PET). PET is a molecular imaging modality that collects pairs of coincident (temporally correlated) annihilation photons emitted from the patient body. The annihilation photon detector typically comprises a scintillation crystal coupled to a fast photo-detector. ToF information provides better localization of the annihilation event along the line formed by each detector pair, resulting in an overall improvement in signal to noise ratio (SNR) of the reconstructed image. Apart from the demand for high luminosity and fast decay time of the scintillation crystal, proper design and selection of the photo-detector and methods for arrival time pick-off are a prerequisite for achieving excellent time resolution required for ToF-PET. We review the two types of photo-detectors used in ToF-PET: photomultiplier tubes (PMTs) and silicon photo-multipliers (SiPMs) with a special focus on SiPMs

Interactive effects of mGlu5 and 5-HT2A receptors on locomotor activity in mice

RationaleMetabotropic glutamate (mGlu) receptors have been suggested to play a role in neuropsychiatric disorders including schizophrenia, drug abuse, and depression. Because serotonergic hallucinogens increase glutamate release and mGlu receptors modulate the response to serotonin (5-HT)(2A) activation, the interactions between serotonin 5-HT(2A) receptors and mGlu receptors may prove to be important for our understanding of these diseases.ObjectiveWe tested the effects of the serotonergic hallucinogen and 5-HT(2A) agonist, 2,5-dimethoxy-4-methylamphetamine (DOM), and the selective 5-HT(2A) antagonist, M100907, on locomotor activity in the mouse behavioral pattern monitor (BPM) in mGlu5 wild-type (WT) and knockout (KO) mice on a C57 background.ResultsBoth male and female mGlu5 KO mice showed locomotor hyperactivity and diminished locomotor habituation compared with their WT counterparts. Similarly, the mGlu5-negative allosteric modulator 2-methyl-6-(phenylethynyl)pyridine (MPEP) also increased locomotor hyperactivity, which was absent in mGlu5 KO mice. The locomotor hyperactivity in mGlu5 receptor KO mice was potentiated by DOM (0.5 mg/kg, subcutaneously (SC)) and attenuated by M100907 (1.0 mg/kg, SC). M100907 (0.1 mg/kg, SC) also blocked the hyperactivity induced by MPEP.ConclusionsThese studies demonstrated that loss of mGlu5 receptor activity either pharmacologically or through gene deletion leads to locomotor hyperactivity in mice. Additionally, the gene deletion of mGlu5 receptors increased the behavioral response to the 5-HT(2A) agonist DOM, suggesting that mGlu5 receptors either mitigate the behavioral effects of 5-HT(2A) hallucinogens or that mGlu5 KO mice show an increased sensitivity to 5-HT(2A) agonists. Taken together, these studies indicate a functional interaction between mGlu5 and 5-HT(2A) receptors

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

A pan-European epidemiological study reveals honey bee colony survival depends on beekeeper education and disease control

Reports of honey bee population decline has spurred many national efforts to understand the extent of the problem and to identify causative or associated factors. However, our collective understanding of the factors has been hampered by a lack of joined up trans-national effort. Moreover, the impacts of beekeeper knowledge and beekeeping management practices have often been overlooked, despite honey bees being a managed pollinator. Here, we established a standardised active monitoring network for 5 798 apiaries over two consecutive years to quantify honey bee colony mortality across 17 European countries. Our data demonstrate that overwinter losses ranged between 2% and 32%, and that high summer losses were likely to follow high winter losses. Multivariate Poisson regression models revealed that hobbyist beekeepers with small apiaries and little experience in beekeeping had double the winter mortality rate when compared to professional beekeepers. Furthermore, honey bees kept by professional beekeepers never showed signs of disease, unlike apiaries from hobbyist beekeepers that had symptoms of bacterial infection and heavy Varroa infestation. Our data highlight beekeeper background and apicultural practices as major drivers of honey bee colony losses. The benefits of conducting trans-national monitoring schemes and improving beekeeper training are discussed

ANALISIS KESESUAIAN KAWASAN WISATA PANTAI PASIR PUTIH DI KECAMATAN KAKULUK MESAK KABUPATEN BELU

Abstrak - Kegiatan wisata pantai Pasir Putih di Kecamatan Kakuluk Mesak mampu menunjang perekonomian masyarakat sekitar pantai, namun jika tidak dikelola berdasarkan kesesuaian dan daya dukung kawasan maka akan memberikan dampak yang tidak berkelanjutan baik pada sisi lingkungan, aktivitas wisata maupun pendapatan masyarakat. Untuk itu penelitian ini bertujuan untuk mengetahui nilai kesesuaian wisata pantai Pasir Putih di Kecamatan Kakuluk Mesak, Kabupaten Belu. Pengambilan data dilakukan pada bulan Juni-Juli 2021 di kawasan wisata pantai Pasir Putih dengan pembagian lokasi pengambilan data menjadi empat lokasi pengamatan dan menggunakan teknik purposive sampling dalam penentuan lokasinya. Metode yang digunakan dalam penelitian adalah metode deskriptif kuantitatif yaitu memberikan gambaran terhadap keadaan yang sebenarnya. Parameter kesesuaian yang dinilai dalam penelitian ini diantaranya kedalaman perairan, kecerahan perairan, kecepatan arus, tipe pantai, lebar pantai, substrat dasar perairan, penutupan lahan, kemiringan pantai, biota berbahaya, dan ketersediaan air tawar. Hasil penelitian menunjukkan bahwa lokasi satu dan lokasi empat termasuk dalam kategori sangat sesuai (S1) untuk kegiatan wisata pantai dengan memiliki nilai kesesuaian wisata yang sama sebesar 86%; sedangkan lokasi dua dan lokasi tiga dikategorikan sesuai (S2) untuk dilakukan kegiatan wisata pantai dengan masing-masing nilai kesesuaian wisata sebesar 75% dan 81%. Dengan demikian, kegiatan wisata pantai yang ada di pantai Pasir Putih sudah sesuai dengan parameter kesesuaian wisata pantai. Kata Kunci: Kesesuaian, Wisata Pantai, Aktivitas Wisata.   Abstract - Pasir Putih beach tourism activities in the Kakuluk Mesak Sub-district can support the economy of the community around the coast, but if it is not managed based on the suitability and carrying capacity of the area, it will have an unsustainable impact on the environment, tourism activities, and community income. For this reason, this study aims to determine the suitability value of Pasir Putih beach tourism in the Kakuluk Mesak Sub-district, Belu Regency. Data collection was carried out in June-July 2021 in the Pasir Putih beach tourist area by dividing the data collection locations into four observation locations and using the purposive sampling technique in determining the location. The method used in this research is a descriptive quantitative method, which is to provide an overview of the actual situation. The suitability parameters assessed in this study include water depth, water brightness, current velocity, beach type, beach width, bottom substrate, land cover, coastal slope, hazardous biota, and freshwater availability. The results showed that location one and location four were included in the very suitable category (S1) for beach tourism activities with the same tourism suitability value of 86%; while location two and location three are categorized according to (S2) for beach tourism activities with tourism suitability values ​​of 75% and 81%, respectively. Thus, beach tourism activities on Pasir Putih beach are under the parameters of suitability of beach tourism. Keywords: Suitability, Beach Tourism, Tourism Activitie