Miracle-dz/UniFAR-FTUs huggingface dataset:
Treating cognitive impairments in primary central nervous system infections: A systematic review of pharmacological interventions

Background: This research synthesized scientific evidence on the use of pharmacotherapy as intervention to reduce cognitive impairments in adult patients with primary central nervous system (CNS) infections. Methods: We searched for experimental studies published in English prior to October 2021 in MEDLINE, Embase and Cochrane databases. We included non-randomized studies (NRS) and randomized control trials (RCT) of pharmacotherapy versus placebo, drug, or a combination of drugs in adults with primary CNS infection. The certainty of the evidence was rated according to GRADE guidelines. Results: We included 8 RCTs and 1 NRS, involving a total of 805 patients (50.77% male patients; mean age 42.67 ± 10.58) with Lyme disease (LD), herpes simplex virus type 1 (HSV-1), or Creutzfeldt–Jakob disease (CJD) studying the efficacy of antibiotics, antiviral, and non-opioid analgesic drugs, respectively. In patients with LD, antibiotics alone or in combination with other drugs enhanced certain cognitive domains relative to placebo. In patients with HSV-1, the results were inconsistent. In patients with CJD, flupirtine maleate enhanced baseline cognitive scores. The quality of RCT studies was low, and the quality of NRS of intervention was very low, suggesting low and very low certainty in the reported results. Conclusion: There is limited evidence and low certainty regarding the efficacy of antimicrobials and analgesics in reducing cognitive impairments in patients with LD, HSV-1, and CJD. Future efforts must be aimed at enhancing attention to clinical trial methodology and reporting, as well as reaching a consensus on outcome measures and the endpoint of clinical trials relevant to patients.
Network-centric emergency response: The challenges of training for a new command and control paradigm

The last two decades have seen technological innovations that have revolutionized the collection and transfer of information, permitting access to and dissemination of massive amounts of data with unprecedented speed and efficiency. These innovations have been incorporated into virtually every aspect of modern society, from personal communications, to commercial and business processes, to governmental function and military operations. The concept of network-centric warfare (NCW) grew out of these new capabilities and has been a prominent topic in strategic and operational discussions in the US military since the late 1990s. In recent years, the concepts behind NCW have been increasingly applied to emergency response, particularly as responders prepare for an increasingly complex threat spectrum in a post-9/11 world. As emergency responders adopt the technological innovations and organizational concepts that enable network-centric operations, attention should be paid to the lessons learned by the US armed forces in the application of the network-centric approach to war-fighting. Emergency operations centers (EOCs), incident command centers (ICCs), and field personnel will require extensive training and experimentation to sort out the impact of this new technology. They must develop protocols and procedures to leverage maximum advantage, while avoiding the undesirable and damaging effects of that technology improperly applied. Because most emergency response organizations lack the vast training resources of the US military, they must be innovative and adaptable in taking advantage of every opportunity to train their personnel in the assimilation of this new technology.
Developing an astrocyte-selective AAV-ADAMTS4 gene therapy to promote repair after spinal cord injury

Spinal cord injury (SCI) affects an estimated 2.5 million people worldwide yet no effective regenerative therapies are available to victims. Astrocytes play a critical role in the secondary injury pathogenesis of SCI. Reactive astrocytes are key contributors to the deposition of chondroitin sulphate proteoglycans (CSPGs) after injury, which are potent inhibitors to axon regeneration and plasticity. A disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4) is a human enzyme that catalyses the proteolysis of CSPG protein cores. Infusion of ADAMTS4 into the damaged spinal cord was previously shown to improve functional recovery after SCI; however, this therapy is limited in its enzyme form. Gene therapy is a method that allows for long-term expression of therapeutic molecules. Adeno-associated viral (AAV) vector gene therapy, in particular, has emerged as the vector of choice for safe, robust and long-term transgene expression in the central nervous system (CNS). Since astrocytes play an important role in SCI pathology, the first objective of this thesis involved the creation of an AAV vector capable of producing robust transgene expression selectively in spinal cord astrocytes. An expression cassette containing a destabilised yellow fluorescent reporter (dYFP) reporter transgene under the control of a GFAP promoter was packaged into the astrocyte tropic AAV serotypes: AAV5, AAV9, and AAVRec2. In cell culture and slice culture experiments, AAV5 was superior in terms of transduction efficiency, transgene expression, and astrocyte selectivity. Due to the packaging constraints of AAV vectors, an additional AAV5 vector was created that contained the shorter GFAP variant GfaABC1D, which equalled the qualities observed by the full-sized promoter. In a clinically relevant rodent model of spinal cord contusion injury, AAV5 vectors with either promoter elicited robust, widespread, astrocyte-selective transgene expression without negatively impacting behavioural scores. An expression cassette containing the ADAMTS4 gene under the control of the GfaABC1D promoter was subsequently packaged into an AAV5 vector for astrocyte-mediated degradation of CSPGs in vitro and in vivo. Sustained expression of ADAMTS4 expression was achieved in vivo, which led to widespread degradation of CSPGs. AAV-ADAMTS4 resulted in significantly decreased lesion size, increased neuroplasticity and improved functional recovery after moderate contusive SCI. Whilst histologically, the effects of AAV-ADAMTS4 appeared to be large, improvements to motor functions were only modest. The last objective included hindlimb-specific exercise rehabilitation as a method to drive and strengthen the formation of beneficial connections whilst pruning aberrant connections. Indeed, the combination of hindlimb rehabilitation with AAV-ADAMTS led to enhanced functional recovery after SCI. Thus, widespread and long-term degradation of CSPGs through AAV-ADAMTS4 gene therapy, from a single administration, represents a promising candidate for clinical translation.
INCREASED PROSTATE SMOOTH MUSCLE CONTRACTIONS AND REDUCED RELAXATIONS IN MIDDLE-AGED RATS.

The increase in elderly population is becoming a worldwide phenomenon. Clinical studies suggest a strong relationship between aging and genitourinary tract diseases, being the benign prostatic hyperplasia (BPH) the most prevalent disease in men [1]. Besides prostate enlargement, BPH is characterized by increased smooth muscle tone, thus contributing to overactive bladder and lower urinary tract symptoms (LUTS). -adrenoceptors are highly expressed in prostate of various animal species. ATP, via purinergic P2X1 receptors, also contributes to the contractile response, and is considered a co-transmitter with noradrenaline in prostate. Other neurotransmitters and signalling regulate the tone of prostatic smooth muscle including Rho-kinase, nitric oxidecGMP and β-adrenoceptor-cAMP pathways. Previous studies showed aging-dependent reduction of prostate nitrergic innervation and distribution of autonomic receptors [2,3]. The aim of the present study was to evaluate the influence of aging in the prostatic smooth muscle (PSM) reactivity in middle-aged rats, looking at both the relaxant and contractile machinery.
The development, nutrition, and management of the young calf

This volume examines the raising of dairy calves, giving an account of all aspects of calf rearing from the rudiments of anatomy and development through the practicalities of feeding and housing. Beginning with an overview of how the calf's digestive system develops, it highlights the period of transition from preruminant to ruminant digestion. The authors provide information necessary to understand the nutritional needs and restrictions during the liquid-feeding phase in the young calf, as well as those factors that govern the development of a functional rumen. Major emphasis is given to the energy and protein requirements of the young calf, with attention to the effects of environmental temperature on energy requirements. The book discusses the management, nutrition, and care of the pregnant cow as well as calving management necessary to deliver a healthy calf. Other topics include liquid feeding systems, formulation and use of milk replacers and starter feeds, the weaning process, housing principles, and the interactions of nutrition and disease.
A Comparison of High-Dose Cytarabine During Induction Versus Consolidation Therapy in Newly Diagnosed AML

Abstract The proportion of patients with acute myeloid leukemia (AML) cured is increased by administering high-dose cytarabine (HiDAC). It remains uncertain whether to administer HiDAC as induction or consolidation, and whether ≥1 cycle of HiDAC is required. Our retrospective study of 416 adult AML patients, excluding good risk cytogenetics, compared a single cycle of HiDAC-based therapy followed by 2 cycles of standard-dose cytarabine (SDAC) (HiDAC induction cohort) with SDAC-based chemotherapy followed by 2 cycles of HiDAC-based chemotherapy (HiDAC consolidation cohort). Complete remission (CR) rate was greater in the HiDAC induction cohort (90% vs 78%, P < 0.01) which did not lead to an improved overall survival (48% vs 43%, P = 0.18) or disease-free survival (DFS) (39% vs 45%, P = 0.95). We noted that, after censoring for allogeneic hematopoetic stem cell transplant (alloHSCT) in CR1, the cumulative incidence of relapse was lower in the HiDAC consolidation cohort in patients with intermediate risk cytogenetics (68% vs 44%, P = 0.01), which lead to a greater DFS (30% vs 47%, P = 0.095). In the patients with adverse risk cytogenetics, the RR was numerically greater in the HiDAC consolidation cohort (52% vs 80%, P = 0.60) which lead to a lower DFS (27% vs 4%, P = 0.11). Our data show that, although the HiDAC induction cohort (1 cycle of HiDAC) achieved a greater CR rate, there were no overall survival differences between the 2 cohorts, and that the HiDAC consolidation cohort (2 cycles of HiDAC) had a lower RR and greater DFS in those patients with intermediate risk cytogenetics who did not undergo alloHSCT in CR1.
The value of routinely combining the Rotterdam European Randomized Study of Screening for Prostate Cancer Risk Calculators with multiparametric magnetic resonance imaging to predict clinically significant prostate cancer remains uncertain

Multiparametric magnetic resonance imaging (mpMRI) has emerged as a most useful tool for triaging patients with a suspicion of harbouring prostate cancer (PCa). mpMRI findings are ranked by the Prostate Imaging Reporting and Data System (PI-RADS) which has been refined into the current PI-RADs 2 version, this topic having been reviewed recently by Roberts et al . in 2018 (1). mpMRI also has the ability to localise non-palpable cancer within the prostate, which if performed before a prostate biopsy will increase the diagnosis of significant PCa (2-4).
Is wet cupping effective in decreasing persistent nonspecific low back pain in adults

Objective: The objective of this selective EBM review is to determine whether or not “Is wet cupping effective in decreasing persistent nonspecific low back pain in adults? ” Study Design: Review of 3 RCTs published between 2009current, all in the English language. Data Sources: Three RCTs analyzed the effectiveness of wet cupping on the reduction of persistent nonspecific low back pain (PNSLBP) compared to a control group using other various analgesic therapies. All studies were found on EBSCOhost and were selected based on relevance to the question and being a POEM. Outcomes measured: All of the articles analyzed the effectiveness of wet cupping in decreasing persistent nonspecific low back pain. The Present Pain Intensity Scale (PPI), Medication Quantification Scale (MQS), Oswestry Disability Questionnaire/Index (ODQ/ODI), and Numeric Rating Scale (NRS). Statistical significance was measured using ANCOVA, Wilcoxon rank-sum test, independent t tests, and NNT. Results: All 3 studies showed a statistically significant decrease in low back pain post intervention on at least one measured outcome. Farhadi et al found a statistically significant change (p<0.01) on all 3 scales at 3 months post intervention. Albedah et al also found that there was a statistically significant decrease in low back pain (p=0.0001) on all 3 scales at both primary end point and follow up. Kim et al showed that this decrease was not significant on the NRS scale, both at primary end point (p=0.37) and follow up (p=0.15), as well as the ODQ scale at both points of analysis (p>0.05). There was a significant decrease in low back pain on the PPI scale at both primary end point and follow up (p<0.01). Conclusion: The RCTs discussed in this review suggest that wet cupping may be an effective treatment for PNSLBP. The inconclusive results in Kim et al complicate the ability to confirm or rebut the hypothesis. Further studies are also warranted to implement a placebo effect, determine the number of sessions for maximum length of analgesia, as well as utilize wet cupping as an additional treatment to other forms of therapeutic modalities.
Effect of Nepeta bracteata Benth. on Chronic Obstructive Pulmonary Disease: A Triple-Blinded, Randomized Clinical Trial

Background: Chronic obstructive pulmonary disease (COPD) imposes a substantial, direct, and indirect economic burden and health complications on healthcare systems. It seems that Persian medicine could facilitate the process of new drug discoveries through reverse pharmacology for the treatment of chronic respiratory diseases. Objectives: This study aimed to determine the preliminary efficacy of Nepeta bracteata Benth. (N. bracteata) in patients with mild to moderate COPD. Methods: In a four-week, triple-blind, randomized, placebo-controlled trial, 78 patients with mild to moderate COPD were randomly allocated to receive either 10 ml syrup of N. bracteata or placebo three times a day, as an add-on to their routine treatment (longacting beta2-agonist and inhaled corticosteroid). The Spirometry was performed on patients at baseline and end of the intervention to evaluate the effect of the treatment. Forced Expiratory Volume in the first second (FEV1) and FEV1/Forced Vital Capacity (FVC) ratio were considered the primary outcomes. COPD Assessment Test (CAT) was also used for the subjective evaluation of patients’ responses. Results: 64 patients completed the study. The results showed a significant improvement in the CAT score in the N. bracteata group (-9.05) compared to the placebo (-2.78) and control (-2.05) groups (P value = 0.001). The comparison of FEV1 and FEV1/FVC changes showed a significant difference in the N. bracteata group. However, when comparing the three groups, the difference was not statistically significant at the beginning and four weeks after the intervention. Conclusions: It seems that the appropriate response of COPD patients to this drug, especially regarding the quality of life, could make it a choice for complementary therapy in chronic respiratory diseases.
LES HISTONES DEACETYLASES DE TOXOPLASMA GONDII : IMPLICATION DANS LA PHYSIOLOGIE DES APICOMPLEXES ET EVALUATION EN TANT QUE NOUVELLES CIBLES THERAPEUTIQUES

Les modifications d'histones chez T. gondii representent un des mecanismes majeurs pour controler la transcription des genes et l'acetylation de certaines histones est impliquee dans le phenomene de differenciation parasitaire qu'est l'interconversion. Nous avons utilise un inhibiteur d'histones deacetylases, FR235222, comme outil afin de clarifier l'implication de l'acetylation des histones chez T. gondii. Le sequencage d'un mutant resistant a la FR235222 a permis d'identifier TgHDAC3 comme cible preferentielle de cet iHDAC. Le domaine d'interaction est specifique de la famille des Apicomplexa ce qui explique la selectivite de cette molecule pour T. gondii et d'autres Apicomplexes dont Plasmodium sp. Sur tachyzoites traites, FR235222 augmente le taux d'acetylation des histones de certains genes dont 1/3 est specifique des stades sporozoites ou bradyzoites avec une surexpression de ces genes apres traitement par FR235222. L'activite antiparasitaire de differents iHDAC a ete testee parallelement sur les deux stades importants en pathologie humaine: le tachyzoite et le kyste. Sur le tachyzoite, seuls les tetrapeptides cycliques presentent une forte activite antiparasitaire avec des EC50 d'environ 10 nM. Les kystes ex-vivo traites avec FR235222, sont non infectants: absence de toxoplasmose chez la souris re-inoculee avec ces kystes. En conclusion, FR235222 presente une activite dirigee contre l'HDAC3 de T. gondii et une specificite envers les Apicomplexes. En interferant avec le cycle naturel du parasite, cette molecule induit la mort des tachyzoites in vitro et supprime le pouvoir infectant des kystes in vivo. Ce travail ouvre une voie prometteuse dans la strategie therapeutique des pathologies a Apicomplexes.
Dynamics of networks during absence seizure's on- and offset in rodents and man

Network mechanisms relevant for the generation, maintenance and termination of spike-wave discharges (SWD), the neurophysiological hallmark of absence epilepsy, are still enigmatic and widely discussed. Within the last years, however, improvements in signal analytical techniques, applied to both animal and human fMRI, EEG, MEG, and ECoG data, greatly increased our understanding and challenged several, dogmatic concepts of SWD. This review will summarize these recent data, demonstrating that SWD are not primary generalized, are not sudden and unpredictable events. It will disentangle different functional contributions of structures within the cortico-thalamo-cortical system, relevant for the generation, generalization, maintenance, and termination of SWD and will present a new “network based” scenario for these oscillations. Similarities and differences between rodent and human data are presented demonstrating that in both species a local cortical onset zone of SWD exists, although with different locations; that in both some forms of cortical and thalamic precursor activity can be found, and that SWD occur through repetitive cyclic activity between cortex and thalamus. The focal onset zone in human data could differ between patients with varying spatial and temporal dynamics; in rats the latter is still poorly investigated.
Who cosleeps? Does high maternal body weight and duvet use increase the risk of sudden infant death syndrome when bed sharing?

cosleeps? Does high maternal body weight and duvet use increase the risk of sudden infant death syndrom when The data reported in the present article come from the New Zealand Cot Death Study undertaken between 1987 and 1990 – the first large case-control study done before the worldwide campaign to reduce the modifiable risk factors for sudden infant death syndrome. This was the first study that identified bed sharing as a potential risk factor for sudden infant death syndrome. Many studies have since been pub-lished on the topic. The present report focuses on three factors that have been less studied or have yielded conflicting results: the characteristics of those who bed share; the influence of maternal body weight; and the use of duvets during bed sharing. conjunction bed
Endogenous retroviruses and the immune system

Initial sequencing of the human and mouse genomes revealed that substantial fractions were composed of retroelements (REs) and endogenous retroviruses (ERVs), the latter being relics of ancestral retroviral infection. Further study revealed ERVs constitute up to 10% of many mammalian genomes. Despite this abundance, comparatively little is known about their interactions, beneficial or detrimental, with the host. This thesis details two distinct sets of interactions with the immune system. Firstly, the presentation of ERV-derived peptides to developing lymphocytes was shown to exert a control on the immune response to infection with Friend Virus (FV). A self peptide encoded by an ERV negatively selected a significant fraction of polyclonal FV-specific CD4+ T cells and resulted in an impaired immune response. However, CD4+ T cell-mediated antiviral activity was fully preserved and repertoire analysis revealed a deletional bias according to peptide affinity, resulting in an effective enrichment of high-affinity CD4+ T cells. Thus, ERVs exerted a significant influence on the immune response, a mechanism that may partially contribute to the heterogeneity seen in human immune responses to retroviral infections. Secondly, a requirement for specific antibodies was shown in the control of ERVs. In a range of mice displaying distinct deficiencies in antibody production, products from the intestinal microbiota potentially induce ERV expression. Subsequent recombinational correction of a defective murine leukaemia virus (MLV) results in the emergence of infectious virus. In the long term, this leads to retrovirus-induced lymphomas and morbidity. ERVs, therefore, provide a potential link between the intestinal microbiota and a range of pathologies, including cancer. Finally, a new computational tool, REquest, was developed for use in the above studies. REquest allows the mining of retroelement (RE) and ERV expression data from the majority of commercially available human and murine microarray platforms and allows rapid hypothesis testing with publicly available data.
The Role of Drug Transporters in Statin-Induced Myopathy

s: Knauer MJ, Kim RB and Tirona RG. Transport Function and pH Dependant Transport of Organic Anion Transporting Polypeptide 2B1 Transcriptional Start Site Variants. ISSX MDO, Noordwijk Aan Zee, Netherlands, 2012. Knauer MJ, Girdwood AJ, Kim RB and Tirona RG. Regulation of Expression and Transport Function of Organic Anion Transporting Polypeptide 2B1 Transcriptional Start Site Variants. Canadian Society of Pharmacology and Therapeutics, Toronto, ON, 2012. Knauer MJ, Girdwood AJ, Kim RB and Tirona RG. Regulation of Expression and Transport Function of Organic Anion Transporting Polypeptide 2B1 Transcriptional Start Site Variants. AAPS, Washington, DC, 2011.
Anatomy, Histology, and Physiology of the Canine Prostate Gland

The prostate gland is the only male accessory gland in dogs and is responsible for secreting the prostatic fluid. Morphologically, the canine prostate gland lacks differentiation into zones, presenting a uniform parenchyma along the longitudinal axis. The luminal epithelial cells secrete a liquid rich in calcium, citric acid, simple sugars, and different enzymes as a component of the seminal plasma. Since the prostatic diseases are very common in small animal practice, there are many information regarding mechanisms of the different prostatic conditions and lack of information regarding the anatomy, histology, and physiology of the canine prostate gland. Thus, this chapter aims to meticulously describe the anatomy, histology, and physiology of the canine prostate gland.