TH1-Polarized TFH Cells Delay Naturally-Acquired Immunity to Malaria

Humoral immunity is a critical effector arm for protection against malaria but develops only slowly after repeated infections. T cell-mediated regulatory dynamics affect the development of antibody responses to Plasmodium parasites. Here, we hypothesize that T follicular helper cell (TFH) polarization generated by repeated Plasmodium asexual blood-stage infections delays the onset of protective humoral responses. IFN-γ production promotes polarization toward TFH1 and increased generation of regulatory follicular helper cells (TFR). Delineating the mechanisms that drive TH1 polarization will provide clues for appropriate induction of lasting, protective immunity against malaria

In Pursuit of Communication without Broca's or Wernicke's area

This case study presents a treatment approach with innovative software for an individual with apraxia of speech and global aphasia from a severe anoxic injury. This paper proposes that aspects of the ability to communicate are available even when core capacities of the language system are dysfunctional (Willems, Benn, Hagoort, Toni, & Varley, 2011). Most of the literature reports that prognosis is bleak for individuals diagnosed as globally aphasic and remain so at one month post. The expected course of recovery is improved comprehension but little functional speech (Sarno, Silverman & Sands, 1970). As such, this treatment was designed to use non-lexical routes toward communication and thereby achieve a better outcome

Kemampuan Menarik Kesimpulan Berdasarkan Tabel Dan Grafik Fisika Pada Peserta Didik Kelas X(MIA) SMA Barrang Lompo

Penelitian ini adalah penelitian Ex-Post Facto yang bersifat deskriptif-survei Subjek penelitian ini adalah peserta didik kelas X(MIA) SMA Barrang Lompo yang terdaftar pada tahun 2014/2015 dengan jumlah peserta didik 43 orang dengan 21 orang peserta didik sebagai sampel penelitian.Teknik pengumpulan data yang dilakukan dalam penelitan ini adalah data mengenai kemampuan menarik kesimpulan berdasarkan tabel dan grafik peserta didik yang diambil dengan cara memberikan tes uraian tertulis. Pemberian skor dirangkum dengan menggunakan lembar observasi. Data yang terkumpul diolah dengan menggunakan statistik deskriptif untuk memperoleh gambaran secara kuantitatif. Berdasarkan hasil analisis data dan pembahasan diperoleh skor rata-rata kemampuan menarik kesimpulan berdasarkan tabel dan grafik peserta didik adalah sebesar 41,52 dari skor ideal yaitu 60. Dari 21 orang peserta didik, umumnya memiliki kemampuan menarik kesimpulan berdasarkan tabel dan grafik berada pada kateogri sedang

Влияние фосфатных связующих на физико-механические свойства периклазохромитовых огнеупоров

У данній статті наведено та порівняно фізико-механічні властивості периклазо-хромітових матеріалів в залежності від різних типів фосфатних зв’язуючих та введення різних домішок. Визначено, що найбільш раціональним є введення триполіфосфату натрію.In given clause are resulted and the physycal-mechanical properties periclase-cgromite of materials are compared depending on different of types phosphate binding and introduction of the various additives. Is determined, that most rational is the introduction treepolyphosphate sodume

Efficacy and safety of ultra-low dose 0.005% estriol vaginal gel for the treatment of vulvovaginal atrophy in postmenopausal women with early breast cancer treated with nonsteroidal aromatase inhibitors: a phase II, randomized, double-blind, placebo-controlled trial

Objective: To assess the efficacy and safety of ultra-low dose 0.005% estriol vaginal gel in women with breast cancer receiving nonsteroidal aromatase inhibitors (NSAIs) and experiencing treatment-related vulvovaginal symptoms and signs. Methods: Women with hormone receptor-positive early breast cancer receiving NSAIs were randomized to either estriol vaginal gel or placebo for 12 weeks. Vaginal maturation, vaginal pH, and total and individual scores of symptoms and signs of vulvovaginal atrophy were assessed at baseline and at weeks 3 and 12; sexual functioning was also evaluated using the Female Sexual Functioning Index (FSFI) questionnaire, as well as circulating estrogens, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Results: Sixty-one women with a mean age of 59 years were included: 50 received 0.005% estriol vaginal gel and 11 received placebo. Active treatment significantly improved maturation value and pH, vaginal dryness and global scores of symptoms and signs. Active treatment also increased the total FSFI score and all the FSFI domains, with the exception of pain. Small oscillations were observed in FSH and LH, which remained within the postmenopausal range. Estriol levels increased initially and normalized by week 12, and estradiol and estrone remained mostly undetectable throughout the study. Conclusions: Ultra-low dose 0.005% estriol vaginal gel showed efficacy in improving the symptoms and signs of vulvovaginal atrophy. These results, together with minimal oscillations in hormonal levels throughout the treatment, support the use of ultra-low dose 0.005% estriol vaginal gel as a treatment option for vulvovaginal atrophy in women with breast cancer receiving NSAIs with an indication for treatment with vaginal estrogens

IP and virtual assistants

Este artigo considera as implicações dos assistentes virtuais para a lei de propriedade intelectual. A Quarta Revolução Industrial e as consequências da pandemia da COVID-19 foram caracterizada por um aumento no comércio eletrônico por meio do uso de assistentes virtuais (“VAs”). Chatbots como o ChatGPT ou o Bard do Google e alto-falantes inteligentes como a ALEXA, Siri ou Google Assistant podem ser muito úteis para os usuários, aumentando os ganhos de eficiência, economizando tempo e custos. No entanto, os chatbots baseados em IA generativa são alimentados com conjuntos de dados em massa que podem aumentar o risco de violação dos direitos de PI e desafiar os conceitos fundamentais dos direitos de PI relacionados a direitos autorais, marcas registradas, patentes e designs. Constata-se que a lei de PI deve continuar a desenvolver à medida que os VAs desafiam a dinâmica tradicional do mercado.This paper considers the implications of virtual assistants for intellectual property law. The Fourth Industrial Revolution and the aftermath of the COVID-19 pandemic has been characterised by a rise in e-commerce through the use of virtual assistants (‘VAs’). Chatbots such as ChatGPT or Google’s Bard and smart speakers such as ALEXA, Siri or Google Assistant can be very useful for users by increasing efficiency gains, saving time and costs. However, the chatbots that are based on generative AI, are fed on mass data sets that can increase the risk of IP rights infringement and challenge fundamental concepts within IP rights relating to copyright, trade marks, patents and designs. It is found that IP law must continue to develop as VAs challenge traditional market dynamics

Leukemia inhibitory factor promotes human first trimester extravillous trophoblast adhesion to extracellular matrix and secretion of tissue inhibitor of metalloproteinases-1 and -2

BACKGROUND: Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that is essential for blastocyst implantation in mice. It has been suggested that LIF may play a role in human first trimester extravillous trophoblast (EVT) invasion. The aim of the present study was to establish whether LIF induces changes in EVT function related to invasiveness. METHODS: Primary first trimester human EVT cell cultures were treated with/without LIF and the effects on cell adhesion to fibronectin (FN), vitronectin (VN) and laminin (LN) were assessed. Transcript levels of integrin subunits that mediate cell adhesion to these extracellular matrix (ECM) elements were determined by real-time RT-PCR. Matrix metalloproteinase (MMP)2 and MMP9 secretion was assessed by gelatine zymography and tissue inhibitors matrix metalloproteinase (TIMP) -1 and TIMP-2 secretion by enzyme-linked immunosorbent assay. RESULTS: EVT cells showed increased adhesion to FN, VN and LN ECM elements in response to LIF (20, 20 and 29%, respectively, P < 0.05 FN and VN compared to control; and P < 0.001 LN compared to control). Integrin beta(4) mRNA levels decreased by 50% following LIF treatment (P < 0.001 versus control). MMP2 and MMP9 secretion was not affected by LIF but LIF did increase secretion of TIMP-1 and -2 (P < 0.001 versus control). LIF stimulated the phosphorylation of signal transducer and activator of transcription (STAT) 3 protein while it did not affect STAT3 protein abundance. The addition of a LIF inhibitor attenuated the LIF-induced STAT3 phosphorylation in EVT. CONCLUSION: The results suggest that LIF can regulate EVT invasion, suggesting an important role in early placental development

Oxygen, the Janus gas; its effects on human placental development and function

The accumulation of oxygen in the earth's atmosphere enabled metabolic pathways based on high-energy electron transfers that were capable of sustaining complex multicellular organisms to evolve. This advance came at a price, however, for the high reactivity of oxygen posed a major challenge as biological molecules became susceptible to oxidative damage, resulting in potential loss of function. Many extant physiological systems are therefore adapted, and homeostatically regulated, to supply sufficient oxygen to meet energy demands whilst also protecting cells, and mitochondria in particular, from excessive concentrations that could lead to oxidative damage. The invasive form of implantation displayed by the human conceptus presents particular challenges in this respect. During the first trimester, the conceptus develops in a low oxygen environment that favours organogenesis in the embryo, and cell proliferation and angiogenesis in the placenta. Later in pregnancy, higher oxygen concentrations are required to support the rapid growth of the fetus. This transition, which appears unique to the human placenta, must be negotiated safely for a successful pregnancy. Normally, onset of the maternal placental circulation is a progressive periphery-centre phenomenon, and is associated with extensive villous regression to form the chorion laeve. In cases of miscarriage, onset of the circulation is both precocious and disorganized, and excessive placental oxidative stress and villous regression undoubtedly contribute to loss of the pregnancy. Comparison of experimental and in vivo data indicates that fluctuations in placental oxygen concentration are a more powerful stimulus for the generation of oxidative stress than chronic hypoxia alone. Placental oxidative and endoplasmic reticulum stress appear to play key roles in the pathophysiology of complications of pregnancy, such as intrauterine growth restriction and preeclampsia, through their adverse impacts on placental function and growth. Establishing an inviolable maternal blood supply for the second and third trimesters is therefore one of the most crucial aspects of human placentation