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Topical azelaic acid and oral tetracycline were compared in a 6-month double-blind study for treatment of acne vulgaris in 45 male subjects with clinical acne. Their acne was graded, inflamed or non-inflamed, lesions were counted and the density of their skin microflora was measured. Both treatments were of benefit and produced only a few minor side-effects. Although oral tetracycline was more effective than azelaic acid, the differences were only just significant. The average reduction in numbers of cutaneous micrococcaceae and Propionibacterium sp. with azelaic acid treatment was 224 and 30-fold, respectively. In a separate group of 11 male subjects with physiological acne the effect of azelaic acid on sebum excretion rate was assessed, and little change was detected. [ABSTRACT FROM AUTHOR]

Four hundred and twenty patients with moderate to severe acne vulgaris were treated with oral erythromycin and topical benzoyl peroxide to determine the optimum dose regimes. Our results show that the response was significantly less in patients with a greater severity of acne, with truncal acne and in those with a higher sebum excretion rate. There was a significantly better clinical result in patients given 1g erythromycin daily than in those given 0.5 g daily (plus topical therapy in both groups). The relapse rate on stopping antibiotics is also significantly less in patients given 1 g daily and this dosage did not produce any increase in side effects. We suggest that any patient requiring oral antibiotics should initially be given 1 g daily of erythromycin (or tetracycline) for up to six months, plus topical therapy. [ABSTRACT FROM AUTHOR]

Despite significant advancements in ocular drug delivery, challenges persist in treating posterior segment diseases like macular edema (ME) and age-related macular degeneration (AMD). Suprachoroidal (SC) injections are a promising new method for targeted drug delivery to the posterior segment of the eye, providing direct access to the choroid and retina while minimizing systemic exposure and side effects. This review examines the anatomical and physiological foundations of the SC space; evaluates delivery devices such as microcatheters, hypodermic needles, and microneedles; and discusses pharmacokinetic principles. Additionally, advancements in gene delivery through SC injections are explored, emphasizing their potential to transform ocular disease management. This review also highlights clinical applications in treating macular edema, diabetic macular edema, age-related macular degeneration, choroidal melanoma, and glaucoma. Overall, SC injections are emerging as a promising novel route for administering ophthalmic treatments, with high bioavailability, reduced systemic exposure, and favorable safety profiles. Key therapeutic agents such as triamcinolone acetonide, dexamethasone, AAV-based gene therapy, and axitinib have shown promise. The field of suprachoroidal injection is progressing rapidly, and this review article, while attempting to encapsulate most of the published preclinical and clinical studies, mainly focuses on those that are published within 2023 and 2024. [ABSTRACT FROM AUTHOR]

Examines the double blind and laboratory trial of tetracycline, oestrogen-cyproterone acetate (OCA) for the treatment of acne. Treatment comparison between the use of tetracycline and OCA; Effectivity of OCA in treating acne among women; Variations of inflammation intensities manifested on inflamed acne lesions.

Forty-eight patients participated in a 3-month double-blind study to compare the effect of orally administered zinc sulphate/citrate complex and tetracycline hydrochloride in acne vulgaris, Tetracycline significantly reduced the overall grade, and the number of non-inflamed lesions, papules and pustules by the third month. It also reduced significantly the non-inflamed lesions and papules at the end of the second month. In contrast, zinc therapy only had a significant effect on the pustules at the third month. The results indicate that tetracycline is far superior to the zinc complex in patients with moderately severe acne. [ABSTRACT FROM AUTHOR]

Greater than 50% of dogs with thyroid tumors present with surgically unresectable disease for which external beam radiotherapy has been reported to prolong survival. The success of131I for control of thyroid tumors in cats and in humans suggests such therapy may also play a role in the management of canine thyroid cancer.Thirty-nine dogs with WHO stage II/III(invasive or ectopic; n = 32) or IV(metastatic; n = 7) thyroid tumors were treated with131I alone. Changes in thyroid function,99MTc-pertechnetate(99MTc) scintigraphic changes, and tumor response were recorded. Dogs with ventral cervical tumors were evaluated for feasibility of surgical resection following131I.Median overall survival was 839 days and 366 days for dogs with stage II/III and stage IV tumors, respectively. Thyroid hormone status, site and surgical resection were not associated with outcome in dogs with stage II/III tumors. Three dogs developed severe bone marrow suppression.These findings suggest131I should be investigated more thoroughly in dogs with thyroid tumors not considered surgical candidates to more clearly characterize the indications for therapy and followup recommendations.131I dosimetry in dogs with thyroid tumors remains problematic. Administration of131I is currently based on empiric recommendations and, in general, the treatment is well tolerated although additional studies are indicated to optimize response and minimize toxicity. [ABSTRACT FROM AUTHOR]

Human African trypanosomiasis is a neglected tropical disease caused by the extracellular protozoan parasite Trypanosoma brucei, and targeted for eradication by 2030. The COVID-19 pandemic contributed to the lengthening of the proposed time frame for eliminating human African trypanosomiasis as control programs were interrupted. Armed with extensive antigenic variation and the depletion of the B cell population during an infectious cycle, attempts to develop a vaccine have remained unachievable. With the absence of a vaccine, control of the disease has relied heavily on intensive screening measures and the use of drugs. The chemotherapeutics previously available for disease management were plagued by issues such as toxicity, resistance, and difficulty in administration. The approval of the latest and first oral drug, fexinidazole, is a major chemotherapeutic achievement for the treatment of human African trypanosomiasis in the past few decades. Timely and accurate diagnosis is essential for effective treatment, while poor compliance and resistance remain outstanding challenges. Drug discovery is on-going, and herein we review the recent advances in anti-trypanosomal drug discovery, including novel potential drug targets. The numerous challenges associated with disease eradication will also be addressed. [ABSTRACT FROM AUTHOR]

Skin conditions are a significant cause of fatal and nonfatal disease burdens globally, ranging from mild irritations to debilitating diseases. Oxidative stress, which is an imbalance between reactive oxygen species and the cells' ability to repair damage, is implicated in various skin diseases. Antioxidants have been studied for their potential benefits in dermatologic health, but the evidence is limited and conflicting. Herein, we conducted a systematic review of controlled trials, meta-analyses, and Cochrane review articles to evaluate the current evidence on the utility of antioxidant supplementation for adjunct prevention and treatment of skin disease and to provide a comprehensive assessment of their role in promoting dermatologic health. The Cochrane Library, PubMed, EMBASE, and Epistemonikos databases were queried. Eligibility criteria included (1) primary focus on nanoparticle utility for skin cancer; (2) includes measurable outcomes data with robust comparators; (3) includes a number of human subjects or cell-line types, where applicable; (4) English language; and (5) archived as full-text journal articles. A total of 55 articles met the eligibility criteria for the present review. Qualitative analysis revealed that topical and oral antioxidant supplementation has demonstrated preliminary efficacy in reducing sunburns, depigmentation, and photoaging. Dietary exogenous antioxidants (namely vitamins A, C, and E) have shown chemopreventive effects against skin cancer. Antioxidant supplementation has also shown efficacy in treating non-cancer dermatoses, including rosacea, psoriasis, atopic dermatitis, and acne vulgaris. While further studies are needed to validate these findings on a larger scale, antioxidant supplementation holds promise for improving skin health and preventing skin diseases. [ABSTRACT FROM AUTHOR]

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition arising in susceptible people, predominantly following viral infection, but also other stressful events. The susceptibility factors discussed here are both genetic and environmental although not well understood. While the dysfunctional physiology in ME/CFS is becoming clearer, understanding has been hampered by different combinations of symptoms in each affected person. A common core set of mainly neurological symptoms forms the modern clinical case definition, in the absence of an accessible molecular diagnostic test. This landscape has prompted interest in whether ME/CFS patients can be classified into a particular phenotype/subtype that might assist better management of their illness and suggest preferred therapeutic options. Currently, the same promising drugs, nutraceuticals, or behavioral therapies available can be beneficial, have no effect, or be detrimental to each individual patient. We have shown that individuals with the same disease profile exhibit unique molecular changes and physiological responses to stress, exercise and even vaccination. Key features of ME/CFS discussed here are the possible mechanisms determining the shift of an immune/inflammatory response from transient to chronic in ME/CFS, and how the brain and CNS manifests the neurological symptoms, likely with activation of its specific immune system and resulting neuroinflammation. The many cases of the post viral ME/CFS-like condition, Long COVID, following SARS-CoV-2 infection, and the intense research interest and investment in understanding this condition, provide exciting opportunities for the development of new therapeutics that will benefit ME/CFS patients. [ABSTRACT FROM AUTHOR]

The role of mechanical signals in the proper functioning of organisms is increasingly recognised, and every cell senses physical forces and responds to them. These forces are generated both from outside the cell or via the sophisticated force-generation machinery of the cell, the cytoskeleton. All regions of the cell are connected via mechanical linkages, enabling the whole cell to function as a mechanical system. In this Review, we define some of the key concepts of how this machinery functions, highlighting the critical requirement for mechanosensory proteins, and conceptualise the coupling of mechanical linkages to mechanochemical switches that enables forces to be converted into biological signals. These mechanical couplings provide a mechanism for how mechanical crosstalk might coordinate the entire cell, its neighbours, extending into whole collections of cells, in tissues and in organs, and ultimately in the coordination and operation of entire organisms. Consequently, many diseases manifest through defects in this machinery, which we map onto schematics of the mechanical linkages within a cell. This mapping approach paves the way for the identification of additional linkages between mechanosignalling pathways and so might identify treatments for diseases, where mechanical connections are affected by mutations or where individual force-regulated components are defective. [ABSTRACT FROM AUTHOR]

Background: Intestinal inflammation is considered to be an important characteristic of ulcerative colitis (UC) and the current medical treatments for UC are usually proposed to suppress abnormal intestinal immune responses. Pulsatilla decoction (PD), a traditional Chinese medicine, is frequently used in UC treatments in Asian countries; however, the mechanism of the action of PD remains unclear. In the present study, the mechanism of the action of PD was elucidated in the dextran sulfate sodium (DSS)-induced colitis mouse model, a model to mimic UC. Methods: Murine colitis was evaluated by comparing the disease activity index score. The intestinal inflammation was examined by histology analyses. The leukocyte infiltration in the colonic tissues was examined by immunohistochemistry analyses. The cytokines level in colonic tissues was examined by Multi-Plex immunoassay. The epithelial proliferation was evaluated by histological analyses. Immunofluorescence double staining was used to examine the expression of MMP-7 in the immune cells. Results: In the DSS-induced colitis mouse model, administration of PD attenuated the intestinal inflammation, with a marked decrease in colonic infiltration of innate immune cells. Immunohistochemical analyses further showed that matrix metalloproteinase-7 (MMP-7) expressed by the infiltrating leukocytes, including neutrophils and macrophages was inhibited by PD treatment. PD increases the cytokine level of IL-6 in colonic tissues. Conclusion: PD suppresses intestinal inflammation, with a marked decrease in colonic infiltration of innate immune cells, through decreasing MMP-7 expression. [ABSTRACT FROM AUTHOR]

The need for new therapeutic approaches for triple-negative breast cancer is a clinically relevant problem that needs to be solved. Using a multi-targeting approach to enhance cancer cell uptake, we synthesized a new family of ruthenium(II) organometallic complexes envisaging simultaneous active and passive targeting, using biotin and polylactide (PLA), respectively. All compounds with the general formula, [Ru(η5-CpR)(P)(2,2′-bipy-4,4′-PLA-biotin)][CF3SO3], where R is -H or -CH3 and P is P(C6H5)3, P(C6H4F)3 or P(C6H4OCH3)3, were tested against triple-negative breast cancer cells MDA-MB-231 showing IC50 values between 2.3–14.6 µM, much better than cisplatin, a classical chemotherapeutic drug, in the same experimental conditions. We selected compound 1 (where R is H and P is P(C6H5)3), for further studies as it was the one showing the best biological effect. In a competitive assay with biotin, we showed that cell uptake via SMVT receptors seems to be the main transport route into the cells for this compound, validating the strategy of including biotin in the design of the compound. The effects of the compound on the hallmarks of cancer show that the compound leads to apoptosis, interferes with proliferation by affecting the formation of cell colonies in a dose-dependent manner and disrupts the cell cytoskeleton. Preliminary in vivo assays in N: NIH(S)II-nu/nu mice show that the concentrations of compound 1 used in this experiment (maximum 4 mg/kg) are safe to use in vivo, although some signs of liver toxicity are already found. In addition, the new compound shows a tendency to control tumor growth, although not significantly. In sum, we showed that compound 1 shows promising anti-cancer effects, bringing a new avenue for triple-negative breast cancer therapy. [ABSTRACT FROM AUTHOR]

The increasingly appreciated prevalence of complicated stressor‐to‐phenotype associations in human disease requires a greater understanding of how specific stressors affect systems or interactome properties. Many currently untreatable diseases arise due to variations in, and through a combination of, multiple stressors of genetic, epigenetic, and environmental nature. Unfortunately, how such stressors lead to a specific disease phenotype or inflict a vulnerability to some cells and tissues but not others remains largely unknown and unsatisfactorily addressed. Analysis of cell‐ and tissue‐specific interactome networks may shed light on organization of biological systems and subsequently to disease vulnerabilities. However, deriving human interactomes across different cell and disease contexts remains a challenge. To this end, this opinion article links stressor‐induced protein interactome network perturbations to the formation of pathologic scaffolds termed epichaperomes, revealing a viable and reproducible experimental solution to obtaining rigorous context‐dependent interactomes. This article presents our views on how a specialized 'omics platform called epichaperomics may complement and enhance the currently available conventional approaches and aid the scientific community in defining, understanding, and ultimately controlling interactome networks of complex diseases such as Alzheimer's disease. Ultimately, this approach may aid the transition from a limited single‐alteration perspective in disease to a comprehensive network‐based mindset, which we posit will result in precision medicine paradigms for disease diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Recently, immunotherapy has been served as the treatment of choice for various human pathophysiologies, including inflammatory diseases and cancer. Though most of the current approaches target the lymphoid compartment, macrophages intimately implicated in the induction or resolution of inflammation have rationally gained their place into the therapeutics arena. In this review, I discuss the past and novel ground‐breaking strategies focusing on macrophages in different human diseases and highlight the current challenges and considerations underlying their translational potentials. [ABSTRACT FROM AUTHOR]

Humans have been dealing with health problems for millions of years. Normal health services need well-trained personnel and high-cost diagnostic tests, which forces patients to go to hospitals if medical treatment is required. To address this, prototype testing has been carried out into the wearable drug delivery health care perspectives. Researchers have devised a wide variety of formulations for the treatment of various diseases at home by performing real-time monitoring of different routes of drug administration such as ocular, transdermal, intraoral, intracochlear, and several more. A comprehensive review of the different types of wearable drug delivery systems with respect to their manufacturing, mechanism of action and specifications has been done. In the pharmaceutical context, these devices are technologically well-equipped interfaces for diverse physicochemical signals. Above mentioned information with a broader perspective has also been discussed in this article. Several wearable drug delivery systems have been introduced in the market in recent years. But a lot of testing needs to be conducted to address the numerous obstacles before the wearable devices are successfully launched in the market. [ABSTRACT FROM AUTHOR]

In the United States, transgender women are disproportionately affected by HIV. However, few evidence-based prevention interventions exist for this key population. We describe two promising, locally developed interventions that are currently being implemented and evaluated through the Centers for Disease Control and Prevention Combination HIV Prevention for Transgender Women Project: (a) ChiCAS, designed to promote the uptake of pre-exposure prophylaxis (PrEP), condom use, and medically supervised hormone therapy among Spanish-speaking transgender Latinas, and (b) TransLife Care, designed to address the structural drivers of HIV risk through access to housing, employment, legal services, and medical services, including HIV preventive care (e.g., PrEP use) among racially/ethnically diverse urban transgender women. If the evaluation trials determine that these interventions are effective, they will be among the first such interventions for use with transgender women incorporating PrEP, thereby contributing to the evidence-based resources that may be used to reduce HIV risk among this population. [ABSTRACT FROM AUTHOR]

Research into the basic biology of human health and disease, as well as translational human research and clinical applications, all benefit from the growing accessibility and versatility of mass spectrometry (MS)-based proteomics. Although once limited in throughput and sensitivity, proteomic studies have quickly grown in scope and scale over the last decade due to significant advances in instrumentation, computational approaches, and bio-sample preparation. Here, we review these latest developments in MS and highlight how these techniques are used to study the mechanisms, diagnosis, and treatment of human diseases. We first describe recent groundbreaking technological advancements for MS-based proteomics, including novel data acquisition techniques and protein quantification approaches. Next, we describe innovations that enable the unprecedented depth of coverage in protein signaling and spatiotemporal protein distributions, including studies of post-translational modifications, protein turnover, and single-cell proteomics. Finally, we explore new workflows to investigate protein complexes and structures, and we present new approaches for protein--protein interaction studies and intact protein or top-down MS. While these approaches are only recently incipient, we anticipate that their use in biomedical MS proteomics research will offer actionable discoveries for the improvement of human health. [ABSTRACT FROM AUTHOR]

Although palmitoylation regulates numerous cellular processes, as yet efforts to manipulate this post-translational modification for therapeutic gain have proved unsuccessful. The Na-pump accessory sub-unit phospholemman (PLM) is palmitoylated by zDHHC5. Here, we show that PLM palmitoylation is facilitated by recruitment of the Na-pump α sub-unit to a specific site on zDHHC5 that contains a juxtamembrane amphipathic helix. Site-specific palmitoylation and GlcNAcylation of this helix increased binding between the Na-pump and zDHHC5, promoting PLM palmitoylation. In contrast, disruption of the zDHHC5-Na-pump interaction with a cell penetrating peptide reduced PLM palmitoylation. Our results suggest that by manipulating the recruitment of specific substrates to particular zDHHC-palmitoyl acyl transferases, the palmitoylation status of individual proteins can be selectively altered, thus opening the door to the development of molecular modulators of protein palmitoylation for the treatment of disease. The Na-pump accessory sub-unit phospholemman (PLM) is palmitoylated by the acyltransferase zDHHC5. Plain & Howie et al identify a binding site on zDHHC5 for the Na-pump, discover that the interaction is regulated by post-translational modifications near this binding site, and find that disrupting the zDHHC5-Na-pump interaction reduces PLM palmitoylation. [ABSTRACT FROM AUTHOR]

Recurrent laryngeal papillomatosis is a disease caused by human papillomaviruses (HPVs), which currently does not benefit from a curative treatment. Due to the fact that HPV has the action of modifying cellular DNA, with changes in the expression of interleukins and interferon, with insufficient maturation of T cells and intracellular overpopulation of immunosuppressive cells, the association of RRP (Recurrent Respiratory Papillomatosis) with an autoimmune disease may cause particular difficulties in the therapeutic management of patients diagnosed with RRP. Immunosuppressive medication negatively influences the development of papillomatosis, increasing the number of local relapses and, respectively, the need for surgical intervention due to the increased viral multiplication and the proliferation of papillomatous lesions. In order to exemplify the difficulties encountered in treating RRP associated with an autoimmune disorder, the authors present the case of a 21-year-old patient diagnosed with juvenile recurrent laryngeal papillomatosis genotype 6, with multiple antecedent surgeries, who was diagnosed with pemphigus vulgaris at the age of 19. The peculiarity of the case lies in the difficulty of managing the RRP associated with an immunosuppressive disorder whose therapeutic indication is cortisone and immunosuppressive treatment, which led to exacerbation of viral multiplication and proliferation of papillomatous lesions. [ABSTRACT FROM AUTHOR]

Alpha (α)-herpesviruses (HSV-1 and HSV-2), like other viruses, are obligate intracellular parasites. They hijack the cellular machinery to survive and replicate through evading the defensive responses by the host. The viral genome of herpes simplex viruses (HSVs) contains viral genes, the products of which are destined to exploit the host apparatus for their own existence. Cellular modulations begin from the entry point itself. The two main gateways that the virus has to penetrate are the cell membrane and the nuclear membrane. Changes in the cell membrane are triggered when the glycoproteins of HSV interact with the surface receptors of the host cell, and from here, the components of the cytoskeleton take over. The rearrangement in the cytoskeleton components help the virus to enter as well as transport to the nucleus and back to the cell membrane to spread out to the other cells. The entire carriage process is also mediated by the motor proteins of the kinesin and dynein superfamily and is directed by the viral tegument proteins. Also, the virus captures the cell's most efficient cargo carrying system, the endoplasmic reticulum (ER)–Golgi vesicular transport machinery for egress to the cell membrane. For these reasons, the host cell has its own checkpoints where the normal functions are halted once a danger is sensed. However, a cell may be prepared for the adversities from an invading virus, and it is simply commendable that the virus has the antidote to these cellular strategies as well. The HSV viral proteins are capable of limiting the use of the transcriptional and translational tools for the cell itself, so that its own transcription and translation pathways remain unhindered. HSV prefers to constrain any self-destruction process of the cell—be it autophagy in the lysosome or apoptosis by the mitochondria, so that it can continue to parasitize the cell for its own survival. This review gives a detailed account of the significance of compartmentalization during HSV pathogenesis. It also highlights the undiscovered areas in the HSV cell biology research which demand attention for devising improved therapeutics against the infection. [ABSTRACT FROM AUTHOR]

Delivery of pharmaceuticals to the posterior segment presents challenges that arise from the anatomy and clearance pharmacokinetics of the eye. Systemic and several local administration options [topical, periocular, intravitreal (IVT) and subretinal] are in clinical use, each with a unique benefit to risk profile shaped by factors including the administered agent, frequency of dosing, achievable pharmaceutical concentrations within posterior segment structures versus elsewhere in the eye or the body, invasiveness of the procedure and the inherent challenges with some administration methods. The use of the suprachoroidal space (SCS), which is the region between the sclera and the choroid, is being explored as a potential approach to target pharmacotherapies to the posterior segment via a minimally invasive injection procedure. Preclinical data on agents such as vascular endothelial growth factor inhibitors and triamcinolone acetonide (TA) indicate that administration via suprachoroidal injection results in more posterior distribution of the pharmacologic agent, with higher exposure to the sclera, choroid, retinal pigment epithelium cells and retina, and lesser exposure to the anterior segment, than observed with IVT administration. Based in part on these findings, clinical trials have explored the efficacy and safety of suprachoroidal administration of pharmacologic therapies in conditions affecting the posterior segment. Data on a proprietary formulation of TA administered by suprachoroidal injection show improvement in anatomic and visual outcomes in subjects with noninfectious uveitis, with the potential to mitigate the known risks of cataract and increased intraocular pressure (IOP) associated with the use of intraocular corticosteroids. Suprachoroidal administration appears to be a promising treatment modality and is also in the early stages of investigation for other possible applications, such as injection of antiglaucoma agents into the anterior SCS for long‐lasting control of elevated IOP, and as a mode of delivery for gene‐ or cell‐based therapies for retinal disorders. [ABSTRACT FROM AUTHOR]

Recent meta-analytic findings have revealed that the addition of motivational interviewing (MI) to cognitive behavior therapy (CBT) for anxiety disorders improves treatment outcome. However, for the most part, previous research has limited MI as a prelude to CBT. This article explored the benefits and complications of a more integrated approach by adapting and examining an already established transdiagnostic CBT protocol to include intermittent MI strategies. The presented protocol is described and illustrated using a case study of a woman meeting criteria for four anxiety disorder diagnoses. This study presents session-by-session treatment accounts, as well as pre, post, and follow-up data. Results indicated clinically significant improvement, supporting the utility of intermittent MI strategies within CBT. Implementation recommendations and future research directions are discussed. [ABSTRACT FROM AUTHOR]

Telomeropathies involve a wide variety of infrequent genetic diseases caused by mutations in the telomerase maintenance mechanism or the DNA damage response (DDR) system. They are considered a family of rare diseases that often share causes, molecular mechanisms and symptoms. Generally, these diseases are not diagnosed until the symptoms are advanced, diminishing the survival time of patients. Although several related syndromes may still be unrecognized this work describes those that are known, highlighting that because they are rare diseases, physicians should be trained in their early diagnosis. The etiology and diagnosis are discussed for each telomeropathy and the treatments when available, along with a new classification of this group of diseases. Ethical and legal issues related to this group of diseases are also considered. [ABSTRACT FROM AUTHOR]

Ubiquitin ligases play an integral role in fine-tuning signaling cascades necessary for normal cell function. Aberrant regulation of ubiquitin ligases has been implicated in several neurodegenerative diseases, generally, due to mutations within the E3 ligase itself. Several proteomic-based methods have recently emerged to facilitate the rapid identification of ligase–substrate pairs—a previously challenging feat due to the transient nature of ligase–substrate interactions. These novel methods complement standard immunoprecipitations (IPs) and include proximity-dependent biotin identification (BioID), ubiquitin ligase–substrate trapping, tandem ubiquitin-binding entities (TUBEs), and a molecular trapping unit known as the NEDDylator. The implementation of these techniques is expected to facilitate the rapid identification of novel substrates of E3 ubiquitin ligases, a process that is likely to enhance our understanding of neurodegenerative diseases and highlight novel therapeutic targets for the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Purpose: This work describes the first live imaging and radiation delivery performed on a prototype 1.0 T inline MRI‐Linac system in a rat brain tumor model, which was conducted on 29 January 2019. Methods: A human scale 1.0 T MRI‐Linac was adapted to be suitable for animal studies via a specially constructed open 6‐channel receiver radiofrequency (RF) coil. A Fischer rat injected with 9L glioma cells in the right hemisphere was imaged and irradiated at day 11 post surgery as part of a larger cohort survival study. The rat was anesthetized and positioned at the iscocenter of the MRI‐Linac. Imaging was used to localize the brain and confirm the presence of a tumor following the administration of a gadolinium nanoparticle contrast agent. A single dose of 10 Gy was delivered using a 2.25 cm × 2.90 cm radiation field covering the whole brain and verified with radiosensitive film in situ. Real‐time imaging was used throughout the irradiation period to monitor the animal and target position. Results: The signal‐to‐noise ratio (SNR) measured in the rat brain was 38. Postcontrast imaging was able to demonstrate a tumor of 5 mm diameter in the upper right hemisphere of the brain approximately 45 min after administration of the nanoparticles. The radiation beam had no impact on SNR and images at the rate of 2 Hz were effective in monitoring both respiration and intrafractional motion. In vivo film dosimetry confirmed the intended dose delivery. The total procedure time was 35 min. Conclusions: We have successfully used MRI guidance to localize and subsequently deliver a radiation field to the whole brain of a rat with a right hemispheric tumor. Real‐time imaging during beam on was of sufficient quality to monitor breathing and perform exception gating of the treatment. This represents the first live use of a high field inline MRI‐Linac. [ABSTRACT FROM AUTHOR]

The article discusses the European Medicines Agency‘s scientific Committee for Medicinal Products for Human Use's (CHMP) opinion on treatment of human African trypanosomiasis (HAT) or sleeping sickness with oral administration of fexinidazole tablets. It stats that the CHMP opinion aimed at evaluation of benefit-risk for medicines relevant to populations outside the European Union.

Iatrogenic common femoral artery pseudoaneurysm is a well-known complication to vascular access. Many options, both surgical and nonsurgical, have been implemented as means to treat pseudoaneurysms such as thrombin injection, image-guided compression, and percutaneous closure devices. This case report demonstrates a novel technique using a VASCADE closure device to successfully treat an iatrogenic common femoral pseudoaneurysm. [ABSTRACT FROM AUTHOR]

This article presents the theoretical, clinical, and practical arguments supporting a process‐based transdiagnostic approach to psychotherapy. A working definition of "psychological process" is provided, as well as a tri‐dimensional categorization of psychological processes potentially involved in psychopathology. Guidelines are proposed to select psychological interventions based on the active psychopathological processes evidenced in a given case. We also provide a rationale to organize treatment as a set of modules, each addressing a specific psychopathological process. Next, we review the main processes that may be active in mood and anxiety disorders, and that are accessible to clinicians in regular practice. For each process, we propose a validated assessment questionnaire. Finally, we offer a free‐access web‐based instrument that allows clients to fill in these questionnaires via an internet survey, and that provides therapists with a tool to easily decode and interpret the questionnaire results and to present them to the clients. [ABSTRACT FROM AUTHOR]

The incidence of cancer is increasing at an alarming rate despite recent advances in prevention strategies, diagnostics and therapeutics for various types of cancer. The identification of novel biomarkers to aid in prognosis and treatment for cancer is urgently required. Uncontrolled proliferation and dysregulated apoptosis are characteristics exhibited by cancer cells in the initiation of various types of cancer. Notably, aberrant expression of crucial oncogenes or cancer suppressors is a defining event in cancer occurrence. Research has demonstrated that SAD1/UNC84 domain protein-2 (SUN2) serves a suppressive role in breast cancer, atypical teratoid/rhabdoid tumors and lung cancer progression. Furthermore, SUN2 inhibits cancer cell proliferation, migration and promotes apoptosis. Recent reports have also shown that SUN2 serves prominent roles in resistance to the excessive DNA damage that destabilizes the genome and promotes cancer development, and these functions of SUN2 are critical for evading initiation of cancer. Additionally, increasing evidence has demonstrated that SUN2 is involved in maintaining cell nuclear structure and appears to be a central component for organizing the natural nuclear architecture in cancer cells. The focus of the present review is to provide an overview on the pharmacological functions of SUN2 in cancers. These findings suggest that SUN2 may serve as a promising therapeutic target and novel predictive marker in various types of cancer. [ABSTRACT FROM AUTHOR]

Since its discovery well over 100 years ago (Flemming, in Sitzungsber Akad Wissensch Wien 71:81-147, 1875; Van Beneden, in Bull Acad R Belg 42:35-97, 1876) the centrosome is increasingly being recognized as a most impactful organelle for its role not only as primary microtubule organizing center (MTOC) but also as a major communication center for signal transduction pathways and as a center for proteolytic activities. Its significance for cell cycle regulation has been well studied and we now also know that centrosome dysfunctions are implicated in numerous diseases and disorders including cancer, Alstrom syndrome, Bardet-Biedl syndrome, Huntington’s disease, reproductive disorders, and several other diseases and disorders. The present review is meant to build on information presented in the previous review (Schatten, in Histochem Cell Biol 129:667-686, 2008) and to highlight functions of the mammalian centrosome in health, and dysfunctions in disorders, disease, and aging with six sections focused on (1) centrosome structure and functions, and new insights into the role of centrosomes in cell cycle progression; (2) the role of centrosomes in tumor initiation and progression; (3) primary cilia, centrosome-primary cilia interactions, and consequences for cell cycle functions in health and disease; (4) transitions from centrosome to non-centrosome functions during cellular polarization; (5) other centrosome dysfunctions associated with the pathogenesis of human disease; and (6) centrosome functions in oocyte germ cells and dysfunctions in reproductive disorders and reproductive aging. [ABSTRACT FROM AUTHOR]

Behçet disease (BD) is an inflammatory systemic disease with a fluctuating course, which can affect the skin, eyes, central nervous system, musculoskeletal, gastrointestinal, and vascular systems. No laboratory tests are currently available for the diagnosis of BD and monitoring disease activity. Moreover there is a lack of knowledge on BD pathogenesis. This study focused on circulating Natural Killer (NK), NKT and T cells evaluated as CD3neg CD56pos, CD3pos CD56pos, and CD3pos CD56neg. Peripheral blood mononuclear cells (PBMCs) were collected from 38 BD patients and 20 healthy controls (HC). The frequencies of NK, NKT, and T cells expressing CD16, CD69, NKG2D, Nkp30, Nkp46, and NKG2A were assessed by flow cytometry. Cytotoxic potential of NK cells was evaluated by flow cytometry as the percentage of cells expressing the degranulation marker CD107a after incubation with K562 cells. The levels of 27 cytokines were determined in plasma with a multiplex bead-based assay. Higher percentages of NK, NKT, and T cells expressing NKG2D were detected in PBMCs of BD patients than HC. ROC curve analysis showed that the evaluation of NKG2Dpos NK, NKT, and T cell percentages discriminated between BD patients and HC. Moreover, there was a positive correlation between the BD Current Activity Form (BDCAF) scores and the frequencies of NKG2Dpos NK and NKT cells. A higher frequency of NK cells expressing CD107a was induced in PBMCs from BD patients than HC after incubation with K562 cells. Concentrations of IL-5, IL-6, IL-10, IL-13, IP-10, and MIP-1β were higher in plasma of BD patients than HC. Monitoring the frequencies of NKG2Dpos lymphocytes could help the clinicians in BD patients management. In addition, the increased expression of NKG2D in BD patients is likely involved in disease pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Although modifying diets, by thickening liquids and modifying the texture of foods, to reduce the risk of aspiration has become central to the current management of dysphagia, the effectiveness of this intervention has been questioned. This narrative review examines, and discusses possible reasons for, the apparent discrepancy between the widespread use of modified diets in current clinical practice and the limited evidence base regarding the benefits and risks of this approach.Discussion: There is no good evidence to date that thickening liquids reduces pneumonia in dysphagia and this intervention may be associated with reduced fluid intake. Texture-modified foods may contribute to undernutrition in those with dysphagia. Modified diets worsen the quality of life of those with dysphagia, and non-compliance is common. There is substantial variability in terminology and standards for modified diets, in the recommendations of individual therapists, and in the consistency of diets prepared by healthcare staff for consumption. Although use of modified diets might appear to have a rational pathophysiological basis in dysphagia, the relationship between aspiration and pneumonia is not clear-cut. Clinical experience may be a more important determinant of everyday practice than research evidence and patient preferences. There are situations in the management of dysphagia where common sense and the necessity of intervention will clearly outweigh any lack of evidence or when application of evidence-based principles can enable good decision making despite the absence of robust evidence. Nevertheless, there is a significant discrepancy between the paucity of the evidence base supporting use of modified diets and the beliefs and practices of practitioners.Conclusion: The disconnect between the limited evidence base and the widespread use of modified diets suggests the need for more careful consideration as to when modified diets might be recommended to patients. Patients (or their representatives) have a choice whether or not to accept a modified diet and must receive adequate information, about the potential risks and impact on quality of life as well as the possible benefits, to make that choice. There is an urgent need for better quality evidence regarding this intervention. [ABSTRACT FROM AUTHOR]

Summary: Mutations in the human LMNA gene cause a collection of diseases known as laminopathies. These include myocardial diseases that exhibit age‐dependent penetrance of dysrhythmias and heart failure. The LMNA gene encodes A‐type lamins, intermediate filaments that support nuclear structure and organize the genome. Mechanisms by which mutant lamins cause age‐dependent heart defects are not well understood. To address this issue, we modeled human disease‐causing mutations in the Drosophila melanogaster Lamin C gene and expressed mutant Lamin C exclusively in the heart. This resulted in progressive cardiac dysfunction, loss of adipose tissue homeostasis, and a shortened adult lifespan. Within cardiac cells, mutant Lamin C aggregated in the cytoplasm, the CncC(Nrf2)/Keap1 redox sensing pathway was activated, mitochondria exhibited abnormal morphology, and the autophagy cargo receptor Ref2(P)/p62 was upregulated. Genetic analyses demonstrated that simultaneous over‐expression of the autophagy kinase Atg1 gene and an RNAi against CncC eliminated the cytoplasmic protein aggregates, restored cardiac function, and lengthened lifespan. These data suggest that simultaneously increasing rates of autophagy and blocking the Nrf2/Keap1 pathway are a potential therapeutic strategy for cardiac laminopathies. [ABSTRACT FROM AUTHOR]

Tunica Interna endothelial cell kinase (Tie2)-expressing macrophages (TEMs) are a subgroup of tumor-associated macrophages that are associated with a poor prognosis in numerous types of cancer. The present study aimed to assess the prognostic impact of Tie2 expression in gastric cancer tissues. Between January 2009 and December 2009, 76 newly diagnosed patients with gastric cancer at the Southwest Hospital, Third Military Medical University (Chongqing, China) were enrolled. TEMs were detected using immunohistochemistry. Tie2, cluster of differentiation (CD)68 and carbonic anhydrase IX (CAIX) were analyzed using immunohistochemistry and immuno- fluorescent microscopy. Tie2 protein expression was analyzed using western blot analysis in hypoxic and normoxic gastric cancer tissues. The number of TEMs positively staining for Tie2 increased with the tumor-node-metastasis (TNM) stage: 0, 53.9, 75.6 and 100% in stages I, II, III and IV, respectively (P<0.001). Tumor size and lymph node involvement were significantly associated with the presence of Tie2 in the tumor stroma (P<0.001). There was no significant difference between Tie2 and CAIX, irrespective of how the patients were grouped (tumor size, lymph node involvement, TNM stage or histological grade). Tie2 protein expression was increased in the hypoxic regions of gastric tumors.Tie2 and CD68 expression colocalized in hypoxic and normoxic gastric cancer tissues. The 1-, 2- and 3-year recurrence rates of the TEM-positive group were 31.4, 56.9 and 66.7%, respectively, as compared with 8, 28 and 48%, respectively, for the TEM-negative group (P<0.05). In the TEM-negative group, 2 patients succumbed to the disease, as compared with 21 patients in the TEM-positive group (P<0.05). Therefore, high quantities of TEMs, represented by Tie2 expression, in gastric tumors may be associated with poor survival. [ABSTRACT FROM AUTHOR]

The fluorinated ornithine analog α-difluoromethylornithine (DFMO, eflornithine, ornidyl) is an irreversible suicide inhibitor of ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine biosynthesis. The ubiquitous and essential polyamines have many functions, but are primarily important for rapidly proliferating cells. Thus, ODC is potentially a drug target for any disease state where rapid growth is a key process leading to pathology. The compound was originally discovered as an anticancer drug, but its effectiveness was disappointing. However, DFMO was successfully developed to treat African sleeping sickness and is currently one of few clinically used drugs to combat this neglected tropical disease. The other Food and Drug Administration (FDA) approved application for DFMO is as an active ingredient in the hair removal cream Vaniqa. In recent years, renewed interest in DFMO for hyperproliferative diseases has led to increased research and promising preclinical and clinical trials. This review explores the use of DFMO for the treatment of African sleeping sickness and hirsutism, as well as its potential as a chemopreventive and chemotherapeutic agent against colorectal cancer and neuroblastoma. [ABSTRACT FROM AUTHOR]

Acne is a multifactorial and inflammatory disease of pilosebaceous follicles, which affects most adolescents. Recent epidemiological data revealed a difference in adults affected by this disease. Women have a high prevalence and incidence when compared with men, especially after 25 years of age. In contrast to what was initially thought, most of these patients do not present endocrinopathy capable of leading to the development of the lesions. When present, polycystic ovarian syndrome is the main cause. However, in these cases, acne is rarely the only dermatological manifestation; hirsutism and acanthosis nigricans are often present. The majority of the normoandrogenic acne patients present a history since adolescence, but in many cases the lesion distribution and intensity change with time. There is often a typical localization of the lesions in the lower third of the face and lateral region of the neck. Another interesting feature is related to the impact on quality of life (QoL), which is always intense. Often there are signs of depression, even when the lesions are mild. As most adult patients are women, in addition to the conventional options, there is also hormone treatment. Combined oral contraceptives and spironolactone are good options. Knowing more about the particularities in etiopathogenesis, impact on QoL, and specific treatment options is important to all dermatologists who face the challenge of treating acne in adults. [ABSTRACT FROM AUTHOR]

Background and Aim A glucagon-like peptide-1 analog, liraglutide, has been reported to block inflammatory somatic pain. We hypothesized that liraglutide attenuates lipopolysaccharide (LPS)-induced and repeated water avoidance stress (WAS)-induced visceral hypersensitivity and tested the hypothesis in rats. Methods The threshold of the visceromotor response induced by colonic balloon distention was measured to assess visceral sensation. Colonic permeability was determined in vivo by quantifying the absorbed Evans blue spectrophotometrically, which was instilled in the proximal colon for 15 min. The interleukin-6 level in colonic mucosa was also quantified using ELISA. Results Subcutaneously injected LPS (1 mg/kg) reduced the visceromotor response threshold after 3 h. Liraglutide (300 μg/kg subcutaneously) at 15 h and 30 min before injecting LPS eliminated LPS-induced allodynia. It also blocked the allodynia induced by repeated water avoidance stress for 1 h for three consecutive days. Neither vagotomy nor naloxone altered the antinociceptive effect of liraglutide, but NG-nitro-L-arginine methyl ester, a nitric oxide synthesis inhibitor, blocked it. LPS increased colonic permeability and the interleukin-6 level, and the analog significantly inhibited these responses. Conclusions This study suggests that liraglutide blocked LPS-induced visceral allodynia, which may be a nitric oxide-dependent response, and was probably mediated by inhibiting pro-inflammatory cytokine production and attenuating the increased gut permeability. Because the LPS-cytokine system is considered to contribute to altered visceral sensation in irritable bowel syndrome, these results indicate the possibility that liraglutide can be useful for treating this disease. [ABSTRACT FROM AUTHOR]

Although juvenile-onset recurrent respiratory papillomatosis (JoRRP) generally involves a benign tumor on the larynx and other respiratory tract areas, almost all patients with this disease require repeated surgical intervention (to prevent airway obstruction during the course of illness) and various adjuvant therapies such as interferon, cidofovir, acyclovir, ribavirin, indole-3-carbinol, HspE7, mumps vaccine, photodynamic therapy, propranolol, cimetidine, and bevacizumab. Some case reports recently described the effectiveness of the quadrivalent human papillomavirus vaccine (HPV4) as an adjuvant therapy. On the basis of these reports, we administered HPV4 to a 2-year-old boy with JoRRP. However, no therapeutic effect was found. A review of the available literature revealed that current evidence for the effectiveness of therapeutic HPV4 and other adjuvant therapies for JoRRP is inconsistent. Therefore, the prophylactic use of currently available HPV vaccine for adolescents is the most effective strategy for preventing not only anogenital cancers but also genital warts, which might be a risk factor for JoRRP among their children in the future. [ABSTRACT FROM AUTHOR]

Objective: Acne vulgaris is the disease of the teenagers as 90% of them being affected. So many treatment modalities are there - systemic, topical and physical . Among them topical therapy is the main stay of treatment. Our study was to determine the efficacy and safety of combination of erythromycin/benzyl peroxide compared with benzyl peroxide alone in the treatment of mild to moderate acne. Method: Patients attended in a Charity Foundation were enrolled for the study after fulfilling the criteria. Among total 50 patients 25 were selected for group A and another 25 for group B.. Group A were treated with 3% erythromycin and 5% Benzyl peroxide combination and GroupB with 5% Benzyl peroxide only. Total acne lesions were counted at base line and after 4, 8 and 12 weeks of follow up. Reduction of total no of lesions were seen and analyzed. Result: At baseline mean of total acne score was 33.60 ± 5.98 and 33.53 ± 5.68 in group A and B (p=0.965). After 12 week it was 2.27 ± 1.08 and 6.27 ± 1.57 respectively in group A and B (p=0.001). Percent reduction of acne severity from base line to final follow up was 93.24 ± 3.11 in group A and 81.17 ± 4.22 in group B (p=0.001). So we can see better reduction of lesion count in Group A than Group B. Conclusion: We conclude that Group A is safer and more effective than that of Group B. So the combination of Benzyl peroxide and erythromycin is better than Benzyl peroxide alone. [ABSTRACT FROM AUTHOR]

Background: Best practices for managing childhood-onset membranous lupus nephritis (MLN) are not yet established. Most studies involve primarily or exclusively adult cohorts or pediatric cohorts with combinations of pure or mixed membranous and proliferative nephritis. Methods: We performed a single-center cohort study of consecutively diagnosed children with pure MLN from 1990 and 2016. Patients received care in Houston, Texas, one of the most diverse metropolitan areas in North America. Renal outcomes were obtained using consensus definitions from the Childhood Arthritis and Rheumatology Research Alliance (CARRA). Logistic regression was used to detect predictors of complete renal response. Results: A total of 56 children with MLN were identified (82% females, 44% black, 35% Hispanic) with a median follow-up time of 4.1 years. The mean age of MLN onset was 13.7 ± 3.4 years. On initial presentation 69% had nephrotic syndrome and 11% had acute kidney injury. Glucocorticoids were prescribed in 96% of patients and anti-malarials in 88%. Mycophenolate mofetil was the most common non-steroid immunosuppressive agent (69%), followed by rituximab (25%), cyclophosphamide (18%), and azathioprine (9%). Renin-angiotensin aldosterone system blocking agents were prescribed in 78% of patients. Of 37 patients with ≥2 years of follow-up, 74% achieved complete renal response at 24 months. No predictor variable of complete renal response was identified in this small cohort. Renal flares occurred in 48% of patients (86% proteinuric, 14% nephritic). On subsequent renal biopsy, 13% patients had developed proliferative nephritis. Conclusions: This single-center cohort of childhood-onset MLN showed favorable outcomes. Utilizing pediatric renal outcomes definitions, we found that response rates were high, as were rates of renal flare. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify predictors of treatment dropout in a sample of gamblers attending a specialist clinic for gambling disorder. We analysed data on 846 treatment-seeking pathological gamblers. Firstly, we investigated differences in socio-demographic and clinical variables between treatment completers and pre-treatment dropouts, as well as between treatment completers and during-treatment dropouts. Subsequently, variables were entered into a multinomial logistic regression model to identify significant predictors of pre-treatment and in-treatment dropout. Overall, 44.8% of clients did not complete the treatment: 27.4% dropped out before starting it, while 17.4% dropped out during the treatment. Younger age and use of drugs were associated with pre-treatment dropout, while family history of gambling disorder, a lower PGSI score, and being a smoker were related with in-treatment dropout. Our findings suggest that pre-treatment dropouts differ from in-treatment dropouts, and, thus, further research will benefit from considering these groups separately. In addition, this newly gained knowledge will also be helpful in increasing treatment retention in specific subgroups of problem gamblers. [ABSTRACT FROM AUTHOR]

Aim: Lactobacillus reuteri is a Gram-positive bacterium that naturally inhabits the human intestinal tract. This study assessed how effectively the probiotic L. reuteri DSM 17938 managed childhood functional abdominal pain (FAP).Methods: We recruited 54 children with a mean age 9.1 ± 3.8 years, who were diagnosed with FAP in the outpatient clinics of three university hospitals in Greece, Slovenia and Poland, according to the Rome III criteria, from January 2013 to December 2015. They were randomly assigned to receive either 2 × 108 colony-forming units of L. reuteri (n = 27) or a placebo (n = 27) for four weeks.Results: Both L. reuteri and the placebo significantly reduced the frequency and intensity of abdominal pain episodes at four and eight weeks compared to baseline (all p < 0.001). L. reuteri decreased the use of pain relieving drugs at four weeks and the number of child school and adult work absences at four and eight weeks, unlike the placebo, which achieved nonsignificant results. However, the difference between the groups did not reach significance. No side effects were recorded.Conclusion: Both L. reuteri and the placebo were effective in alleviating pain in children with FAP, but only L. reuteri improved the child's and family's normal activities. [ABSTRACT FROM AUTHOR]

Evidence-based practice (EBP) has become a central focus in clinical child and adolescent psychology. As originally defined, EBP in psychology is the integration of the best available research evidence, patient characteristics, and clinical expertise. Although evidence-based perspectives have garnered widespread acceptance in recent years, there has also been some confusion and disagreement about the 3-part definition of EBP, particularly the role of research. In this article, we first provide a brief review of the development of EBP in clinical child and adolescent psychology. Next, we outline the following 4 points to help clarify the understanding of EBP: (a) knowledge should not be confused with epistemic processes, (b) research on clinician and client factors is needed for EBP, (c) research on assessment is needed for EBP, and (d) the 3-part conceptualization of EBP can serve as a useful framework to guide research. Based on these principles, we put forth a slightly revised conceptualization of EBP, in which the role of research is expanded and more clearly operationalized. Finally, based on our review of the literature, we offer illustrative examples of specific directions for future research to advance the evidence base for EBP in clinical child and adolescent psychology. [ABSTRACT FROM PUBLISHER]

Human immunodeficiency virus (HIV) is a causative agent of acquired immune deficiency syndrome (AIDS). Highly active antiretroviral therapy (HAART) can slow down the replication of HIV-1, leading to an improvement in the survival of HIV-1-infected patients. However, drug toxicities and poor drug administration has led to the emergence of a drug-resistant strain. HIV-1 immunotherapy has been continuously developed, but antibody therapy and HIV vaccines take time to improve its efficiency and have limitations. HIV-1-specific chimeric antigen receptor (CAR)-based immunotherapy founded on neutralizing antibodies is now being developed. In HIV-1 therapy, anti-HIV chimeric antigen receptors showed promising data in the suppression of HIV-1 replication; however, autologous transfusion is still a problem. This has led to the development of effective peptides and proteins for an alternative HIV-1 treatment. In this paper, we provide a comprehensive review of potent anti-HIV-1 peptides and proteins that reveal promising therapeutic activities. The inhibitory mechanisms of each therapeutic molecule in the different stages of the HIV-1 life cycle will be discussed herein. [ABSTRACT FROM AUTHOR]

Influenza virus causes three to five million severe respiratory infections per year in seasonal epidemics, and sporadic pandemics, three of which occurred in the twentieth century and are a continuing global threat. Currently licensed antivirals exclusively target the viral neuraminidase or M2 ion channel, and emerging drug resistance necessitates the development of novel therapeutics. It is believed that a host-targeted strategy may combat the development of antiviral drug resistance. To this end, a class of molecules known as iminosugars, hydroxylated carbohydrate mimics with the endocyclic oxygen atom replaced by a nitrogen atom, are being investigated for their broad-spectrum antiviral potential. The influenza virus glycoproteins, hemagglutinin and neuraminidase, are susceptible to inhibition of endoplasmic reticulum α-glucosidases by certain iminosugars, leading to reduced virion production or infectivity, demonstrated byin vitroandin vivostudies. In some experiments, viral strain-specific effects are observed. Iminosugars may also inhibit other host and virus targets with antiviral consequences. While investigations of anti-influenza iminosugar activities have been conducted since the 1980s, recent successes of nojirimycin derivatives have re-invigorated investigation of the therapeutic potential of iminosugars as orally available, low cytotoxicity, effective anti-influenza drugs. [ABSTRACT FROM AUTHOR]

Research activity on the potential clinical value of classic hallucinogens and other psychedelics has increased markedly in the past two decades, and promises to continue to expand. Experimental study of hallucinogen-assisted treatment, and any future clinical use, requires the development of psychotherapeutic models that are appropriate to the disorder being treated and effectively integrated with the pharmacologic component of the treatment. To provide a framework for thinking about possible treatment models, we provide an overview of the history of psychedelic-assisted treatment, review what is known about the therapeutic mechanisms of these treatments, and consider the various purposes of psychotherapy in the context of both research and clinical use of psychedelic-assisted treatment. We then provide a description of a therapy model we have developed and are currently using in a trial of psilocybin-assisted treatment for alcoholism. Finally, we discuss advantages and disadvantages of a range of alternative models, emphasizing the need for research to determine the most effective treatment models for any indications for which efficacy becomes established. [ABSTRACT FROM AUTHOR]

Objective The aim of the present study is to assess the bidirectional associations between therapist and client speech during a treatment based on motivational interviewing (MI) for social anxiety disorder. Method Participants were 85 adults diagnosed with social anxiety who received MI prior to entering cognitive behavioral therapy. MI sessions were sequentially coded using the Motivational Interviewing Skill Code 2.5. Results Therapist MI-consistent behaviors, including open questions as well as positive and negative reflections, were more likely to be followed by client change exploration (change talk and counter-change talk). Therapist MI-inconsistent behaviors were more likely to precede client neutral language. Client language was also found to influence therapist likelihood of responding in an MI-consistent manner. Conclusion The findings support the first step of the MI causal model in the context of social anxiety and direct future research into the effect of therapist and client behaviors on MI treatment outcome. [ABSTRACT FROM AUTHOR]

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Background: Behavioral and psychological symptoms of dementia (BPSD) are a group of psychological reactions, psychiatric symptoms, and behaviors commonly found in Alzheimer's disease (AD). Four clusters of BPSD have been described: mood disorders (depression, anxiety, and apathy), psychotic symptoms (delusions and hallucinations), aberrant motor behaviors (pacing, wandering, and other purposeless behaviors), and inappropriate behaviors (agitation, disinhibition, and euphoria). Most of them are attributed to acetylcholine deficiency.Objective: To evaluate if a higher amount of acetylcholine obtained by associating donepezil and choline alphoscerate might have a favorable effect on BPSD.Methods: BPSD were measured at baseline and after 24 months in 113 mild/moderate AD patients, included in the double-blind randomized trial ASCOMALVA, by the Neuropsychiatric Inventory (NPI). Two matched groups were compared: group A treated with donepezil (10 mg/day) plus choline alphoscerate (1200 mg/day), and group B treated with donepezil (10 mg/day) plus placebo.Results: Data of NPI revealed a significant decrease of BPSD severity and distress of the caregiver in patients of group A compared with group B. Mood disorders (depression, anxiety and apathy) were significantly decreased in subjects treated with donepezil and choline alphoscerate, while their severity and frequency was increased in the other group.Conclusions: Patients treated with donepezil plus choline alphoscerate showed a lower level of behavioral disturbances than subjects treated with donepezil only, suggesting that the association can have beneficial effects. [ABSTRACT FROM AUTHOR]

The authors examined the retention rates of 191 participants who were assigned to an episode of substance abuse treatment. Two types of attrition, due to participants withdrawing prematurely from treatment or failing to complete a posttest survey, were investigated. A significant finding of the study was that attrition can be predicted with some certainty. In spite of being a consistent predictor of attrition, however, quantitative measures explained only about 27 % of the variance in therapy outcomes. Therefore, recommendations for future research were included to highlight the importance of exploring the impact of contextual factors on client retention. [ABSTRACT FROM AUTHOR]