Driving CARs into Sweet Roads: Targeting Glycosylated Antigens in Cancer.

Engineering T cells with chimeric antigen receptors (CARs) has demonstrated remarkable success in eradicating hematological malignancies. In this issue of Immunity, June and colleagues demonstrate the broad antitumor efficacy of a newly-designed CAR targeting the O-linked hypoglycosylated epitopes Tn and sialyl-Tn on cancer-associated MUC-1.

The universe of galectin-binding partners and their functions in health and disease.

Galectins, a family of evolutionarily conserved glycan-binding proteins, play key roles in diverse biological processes including tissue repair, adipogenesis, immune cell homeostasis, angiogenesis, and pathogen recognition. Dysregulation of galectins and their ligands has been observed in a wide range of pathologic conditions including cancer, autoimmune inflammation, infection, fibrosis, and metabolic disorders. Through protein-glycan or protein-protein interactions, these endogenous lectins can shape the initiation, perpetuation, and resolution of these processes, suggesting their potential roles in disease monitoring and treatment. However, despite considerable progress, a full understanding of the biology and therapeutic potential of galectins has not been reached due to their diversity, multiplicity of cell targets, and receptor promiscuity. In this article, we discuss the multiple galectin-binding partners present in different cell types, focusing on their contributions to selected physiologic and pathologic settings. Understanding the molecular bases of galectin-ligand interactions, particularly their glycan-dependency, the biochemical nature of selected receptors, and underlying signaling events, might contribute to designing rational therapeutic strategies to control a broad range of pathologic conditions.

Galectin-1 fosters an immunosuppressive microenvironment in colorectal cancer by reprogramming CD8+ regulatory T cells.

Colorectal cancer (CRC) represents the third most common malignancy and the second leading cause of cancer-related deaths worldwide. Although immunotherapy has taken center stage in mainstream oncology, it has shown limited clinical efficacy in CRC, generating an urgent need for discovery of new biomarkers and potential therapeutic targets. Galectin-1 (Gal-1), an endogenous glycan-binding protein, induces tolerogenic programs and contributes to tumor cell evasion of immune responses. Here, we investigated the relevance of Gal-1 in CRC and explored its modulatory activity within the CD8+ regulatory T cell (Treg) compartment. Mice lacking Gal-1 (Lgals1-/- ) developed a lower number of tumors and showed a decreased frequency of a particular population of CD8+CD122+PD-1+ Tregs in the azoxymethane-dextran sodium sulfate model of colitis-associated CRC. Moreover, silencing of tumor-derived Gal-1 in the syngeneic CT26 CRC model resulted in reduced number and attenuated immunosuppressive capacity of CD8+CD122+PD-1+ Tregs, leading to slower tumor growth. Moreover, stromal Gal-1 also influenced the fitness of CD8+ Tregs, highlighting the contribution of both tumor and stromal-derived Gal-1 to this immunoregulatory effect. Finally, bioinformatic analysis of a colorectal adenocarcinoma from The Cancer Genome Atlas dataset revealed a particular signature characterized by high CD8+ Treg score and elevated Gal-1 expression, which delineates poor prognosis in human CRC. Our findings identify CD8+CD122+PD-1+ Tregs as a target of the immunoregulatory activity of Gal-1, suggesting a potential immunotherapeutic strategy for the treatment of CRC.

Translating the 'Sugar Code' into Immune and Vascular Signaling Programs.

The vast range and complexity of glycan structures and their dynamic variations in health and disease have presented formidable challenges toward understanding the biological significance of these molecules. Despite these limitations, compelling evidence highlights a major role for galectins, a family of soluble glycan-binding proteins, as endogenous decoders that translate glycan-containing information into a broad spectrum of cellular responses by modulating receptor clustering, reorganization, endocytosis, and signaling. Here, we underscore pioneer findings and recent advances in understanding the biology of galectin-glycan interactions in myeloid, lymphoid, and endothelial compartments, highlighting important pathways by which these multivalent complexes control immune and vascular programs. Implementation of novel glycoanalytical approaches, as well as the use of genetically engineered cell and organism models, have allowed glycans and galectins to be explored across a range of cellular processes.

Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of severe gastrointestinal and hepatic toxicities from checkpoint inhibitors.

Immune-related adverse events (IrAEs) affecting the gastrointestinal (GI) tract and liver are among the most frequent and most severe inflammatory toxicities from contemporary immunotherapy. Inflammation of the colon and or small intestines (entero)colitis is the single most common GI IrAE and is an important cause of delay of discontinuation of immunotherapy. The severity of these GI IrAEs can range from manageable with symptomatic treatment alone to life-threatening complications, including perforation and liver failure. The frequency and severity of GI IrAEs is dependent on the specific immunotherapy given, with cytotoxic T lymphocyte antigen (CTLA)-4 blockade more likely to induce severe GI IrAEs than blockade of either programmed cell death protein 1 (PD-1) or PD-1 ligand (PD-L1), and combination therapy showing the highest rate of GI IrAEs, particularly in the liver. To date, we have minimal prospective data on the appropriate diagnosis and management of GI IrAEs, and recommendations are based largely on retrospective data and expert opinion. Although clinical diagnoses of GI IrAEs are common, biopsy is the gold standard for diagnosis of both immunotherapy-induced enterocolitis and hepatitis and can play an important role in excluding competing, though less common, diagnoses and ensuring optimal management. GI IrAEs typically respond to high-dose corticosteroids, though a significant fraction of patients requires secondary immune suppression. For colitis, both TNF-α blockade with infliximab and integrin inhibition with vedolizumab have proved highly effective in corticosteroid-refractory cases. Detailed guidelines have been published for the management of low-grade GI IrAEs. In the setting of more severe toxicities, involvement of a GI specialist is generally recommended. The purpose of this review is to survey the available literature and provide management recommendations focused on the GI specialist.

Cancer immunotherapy-related adverse events: causes and challenges.

Despite the success and ongoing promise of monoclonal antibody-targeted immune checkpoint inhibitor immunotherapy of advanced malignancies, in particular, antibodies directed against CTLA-4 and PD-1/PD-L1, the development of immune-related adverse events (irAEs) remains a constraint of this type of therapy. Although rarely fatal, the occurrence of irAEs may necessitate discontinuation of immunotherapy, as well as administration of corticosteroids or other immunosuppressive therapies that may not only compromise efficacy but also predispose for development of opportunistic infection. Clearly, retention of efficacy of immune checkpoint-targeted therapies with concurrent attenuation of immune-mediated toxicity represents a formidable challenge. In this context, the current brief review examines mechanistic relationships between these events, as well as recent insights into immunopathogenesis, and strategies which may contribute to resolving this issue. These sections are preceded by brief overviews of the discovery and functions of CTLA-4 and PD-1, as well as the chronology of the development of immunotherapeutic monoclonal antibodies which target these immune checkpoint inhibitors.

A neutralizing monoclonal antibody-based competitive ELISA for classical swine fever C-strain post-vaccination monitoring.

BACKGROUND: Virus neutralization test (VNT) is widely used for serological survey of classical swine fever (CSF) and efficacy evaluation of CSF vaccines. However, VNT is a time consuming procedure that requires cell culture and live virus manipulation. C-strain CSF vaccine is the most frequently used vaccine for CSF control and prevention. In this study, we presented a neutralizing monoclonal antibody (mAb) based competitive enzyme-linked immunosorbent assay (cELISA) with the emphasis on the replacement of VNT for C-strain post-vaccination monitoring. RESULTS: One monoclonal antibody (6B211) which has potent neutralizing activity against C-strain was generated. A novel cELISA was established and optimized based on the strategy that 6B211 can compete with C-strain induced neutralizing antibodies in pig serum to bind capture antigen C-strain E2. By testing C-strain VNT negative pig sera (n = 445) and C-strain VNT positive pig sera (n = 70), the 6B211 based cELISA showed 100% sensitivity (95% confidence interval: 94.87 to 100%) and 100% specificity (95% confidence interval: 100 to 100%). The C-strain antibody can be tested in pigs as early as 7 days post vaccination with the cELISA. By testing pig sera (n = 139) in parallel, the cELISA showed excellent agreement (Kappa = 0.957) with VNT. The inhibition rate of serum samples in the cELISA is highly correlated with their titers in VNT (r2 = 0.903, p < 0.001). In addition, intra- and inter-assays of the cELISA exhibited acceptable repeatability with low coefficient of variations (CVs). CONCLUSIONS: This novel cELISA demonstrated excellent agreement and high level correlation with VNT. It is a reliable tool for sero-monitoring of C-strain vaccination campaign because it is a rapid, simple, safe and cost effective assay that can be used to monitor vaccination-induced immune response at the population level.

Resistance to coronavirus infection in amino peptidase N-deficient pigs.

The alphacoronaviruses, transmissible gastroenteritis virus (TGEV) and Porcine epidemic diarrhea virus (PEDV) are sources of high morbidity and mortality in neonatal pigs, a consequence of dehydration caused by the infection and necrosis of enterocytes. The biological relevance of amino peptidase N (ANPEP) as a putative receptor for TGEV and PEDV in pigs was evaluated by using CRISPR/Cas9 to edit exon 2 of ANPEP resulting in a premature stop codon. Knockout pigs possessing the null ANPEP phenotype and age matched wild type pigs were challenged with either PEDV or TGEV. Fecal swabs were collected daily from each animal beginning 1 day prior to challenge with PEDV until the termination of the study. The presence of virus nucleic acid was determined by PCR. ANPEP null pigs did not support infection with TGEV, but retained susceptibility to infection with PEDV. Immunohistochemistry confirmed the presence of PEDV reactivity and absence of TGEV reactivity in the enterocytes lining the ileum in ANPEP null pigs. The different receptor requirements for TGEV and PEDV have important implications in the development of new genetic tools for the control of enteric disease in pigs.

Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1.

Galectin-1 (Gal-1), a glycan-binding protein with broad antiinflammatory activities, functions as a proresolving mediator in autoimmune and chronic inflammatory disorders. However, its role in allergic airway inflammation has not yet been elucidated. We evaluated the effects of Gal-1 on eosinophil function and its role in a mouse model of allergic asthma. Allergen exposure resulted in airway recruitment of Gal-1-expressing inflammatory cells, including eosinophils, as well as increased Gal-1 in extracellular spaces in the lungs. In vitro, extracellular Gal-1 exerted divergent effects on eosinophils that were N-glycan- and dose-dependent. At concentrations ≤0.25 µM, Gal-1 increased eosinophil adhesion to vascular cell adhesion molecule-1, caused redistribution of integrin CD49d to the periphery and cell clustering, but inhibited ERK(1/2) activation and eotaxin-1-induced migration. Exposure to concentrations ≥1 µM resulted in ERK(1/2)-dependent apoptosis and disruption of the F-actin cytoskeleton. At lower concentrations, Gal-1 did not alter expression of adhesion molecules (CD49d, CD18, CD11a, CD11b, L-selectin) or of the chemokine receptor CCR3, but decreased CD49d and CCR3 was observed in eosinophils treated with higher concentrations of this lectin. In vivo, allergen-challenged Gal-1-deficient mice exhibited increased recruitment of eosinophils and CD3(+) T lymphocytes in the airways as well as elevated peripheral blood and bone marrow eosinophils relative to corresponding WT mice. Further, these mice had an increased propensity to develop airway hyperresponsiveness and displayed significantly elevated levels of TNF-α in lung tissue. This study suggests that Gal-1 can limit eosinophil recruitment to allergic airways and suppresses airway inflammation by inhibiting cell migration and promoting eosinophil apoptosis.

[Immunotherapy in cancer. Current prospects, challenges and new horizons]. / Inmunoterapia en cáncer. Perspectivas actuales, desafíos y nuevos horizontes.

Recent understanding of the mechanisms that control immune system homeostasis and orchestrate antitumor responses has prompted the development of novel immunotherapeutic modalities. These include antibodies that target immune checkpoints such as PD-1/PD-L1 and CTLA-4, agonistic antibodies of costimulatory molecules such as CD137 and OX-40 and the adoptive transfer of genetically-modified antitumor T cells. However, a large number of patients do not respond to these therapies and develop resistance as a result of activation of compensatory circuits. Rational combination of immunotherapeutic modalities will help overcome resistance and will increase the number of patients who will benefit from these treatments. Moreover, identification of predictive biomarkers will allow selection of patients responding to these treatments. Emerging clinical trials and pre-clinical studies have shown exciting results anticipating new horizons in the design and implementation of cancer immunotherapeutic modalities.

Differential response of myeloid-derived suppressor cells to the nonsteroidal anti-inflammatory agent indomethacin in tumor-associated and tumor-free microenvironments.

Myeloid-derived suppressor cells (MDSCs) are key regulatory cells that control inflammation and promote tumor-immune escape. To date, no specific immunomodulatory drug has proven efficacy in targeting the expansion and/or function of these cells in different pathophysiologic settings. In this study, we identified a context-dependent effect of the nonsteroidal anti-inflammatory drug indomethacin (IND) on MDSCs, depending on whether they were derived from tumor microenvironments (TME) or from tumor-free microenvironments (TFME). Treatment of mice bearing the LP07 lung adenocarcinoma with IND inhibited the suppressive activity of splenic MDSCs, which restrained tumor growth through mechanisms involving CD8(+) T cells. The same effect was observed when MDSCs were treated with IND and conditioned media from LP07 tumor cells in vitro. However, in the absence of a tumor context, IND enhanced the intrinsic suppressive function of MDSCs and amplified their protumoral activity. In a model of autoimmune neuroinflammation, IND-treated MDSCs differentiated in TFME attenuated inflammation, whereas IND-treated MDSCs differentiated in TME aggravated clinical symptoms and delayed resolution of the disease. Mechanistically, IND reduced arginase activity as well as NO and reactive oxygen species production in MDSCs differentiated in TME but not in TFME. Moreover, expression of the C/EBP-ß transcription factor isoforms correlated with the suppressive activity of IND-treated MDSCs. Our study unveils the dual and context-dependent action of IND, a drug that serves both as an anti-inflammatory and anticancer agent, which differentially affects MDSC activity whether these cells are derived from TME or TFME. These results have broad clinical implication in cancer, chronic inflammation and autoimmunity.

Microbiological quality of Argentinian paprika.

The aim of this study was to evaluate the microbiological quality of paprika produced in Catamarca, Argentina. Microbiological analyses were carried out for the enumeration of total aerobic mesophilic bacteria, coliforms, yeasts and molds, and the detection of Salmonella in samples obtained from different local producers during three consecutive years. The mycobiota was identified paying special attention to the mycotoxigenic molds. Standard plate counts of aerobic mesophilic bacteria ranged from 2.7×105 to 3.7×107CFU/g. Coliform counts ranged from <10 to 8.1×104CFU/g. Salmonella was not detected in any of the samples tested. Fungal counts (including yeasts and molds) ranged between 2×102 and 1.9×105CFU/g. These results showed a high level of microbial contamination, exceeding in several samples the maximum limits set in international food regulations. The study of the mycobiota demonstrated that Aspergillus was the predominant genus and Aspergillus niger (potential producer of ochratoxin A) the most frequently isolated species, followed by Aspergillus flavus (potential producer of aflatoxins). Other species of potential toxigenic fungi such as Aspergillus ochraceus, Aspergillus westerdijkiae, Penicillium chrysogenum, Penicillium crustosum, Penicillium commune, Penicillium expansum and Alternaria tenuissima species group were encountered as part of the mycobiota of the paprika samples indicating a risk of mycotoxin contamination. A. westerdijkiae was isolated for the first time in Argentina.

Assembly, organization and regulation of cell-surface receptors by lectin-glycan complexes.

Galectins are a family of ß-galactoside-binding lectins carrying at least one consensus sequence in the carbohydrate-recognition domain. Properties of glycosylated ligands, such as N- and O-glycan branching, LacNAc (N-acetyl-lactosamine) content and the balance of α2,3- and α2,6-linked sialic acid dramatically influence galectin binding to a preferential set of counter-receptors. The presentation of specific glycans in galectin-binding partners is also critical, as proper orientation and clustering of oligosaccharide ligands on multiple carbohydrate side chains increase the binding avidity of galectins for particular glycosylated receptors. When galectins are released from the cells, they typically concentrate on the cell surface and the local matrix, raising their local concentration. Thus galectins can form their own multimers in the extracellular milieu, which in turn cross-link glycoconjugates on the cell surface generating galectin-glycan complexes that modulate intracellular signalling pathways, thus regulating cellular processes such as apoptosis, proliferation, migration and angiogenesis. Subtle changes in receptor expression, rates of protein synthesis, activities of Golgi enzymes, metabolite concentrations supporting glycan biosynthesis, density of glycans, strength of protein-protein interactions at the plasma membrane and stoichiometry may modify galectin-glycan complexes. Although galectins are key contributors to the formation of these extended glycan complexes leading to promotion of receptor segregation/clustering, and inhibition of receptor internalization by surface retention, when these complexes are disrupted, some galectins, particularly galectin-3 and -4, showed the ability to drive clathrin-independent mechanisms of endocytosis. In the present review, we summarize the data available on the assembly, hierarchical organization and regulation of conspicuous galectin-glycan complexes, and their implications in health and disease.

Neoplastic and non-neoplastic lesions in biopsy samples from pet rabbits in Hong Kong: a retrospective analysis, 2019-2022.

Rabbits are popular pets in the urban environment of Hong Kong, ranking third behind cats and dogs. Here we describe the frequency of neoplastic and non-neoplastic lesions in biopsies from pet rabbits submitted to the CityU Veterinary Diagnostic Laboratory between 2019 and 2022, comprising 247 tissue samples from 243 rabbits collected by veterinarians in 19 veterinary clinics. Among the 243 rabbits, there were 128 females (65 spayed), 114 males (54 castrated); sex information was not provided for 1 rabbit. The rabbit breeds included 45 Lionhead, 35 Dwarf, 14 Lop, 11 Dwarf Lop, 5 French Lop, 3 Angora, 2 Dutch, 2 Holland Lop, and 1 each of Netherland Dwarf, Velveteen, Mini Lop, and New Zealand White. The mean ages of rabbits with neoplastic and non-neoplastic lesions were 7.1 and 5.7 y, respectively. The most common neoplastic lesions were adenocarcinoma (26.4%), trichoblastoma (21.4%), sarcoma (9.4%), and thymoma (8.2%). The most common non-neoplastic lesion was uterine cystic endometrial hyperplasia (14.8%), followed by dermal abscess formation in the ventral abdomen or skin of the head (12.5%). Although a broad spectrum of other lesions was described, our findings in biopsies from pet rabbits in Hong Kong are consistent with those in other jurisdictions.

Recognition of the different structural forms of the capsid protein determines the outcome following infection with porcine circovirus type 2.

Porcine circovirus type 2 (PCV2) capsid protein (CP) is the only protein necessary for the formation of the virion capsid, and recombinant CP spontaneously forms virus-like particles (VLPs). Located within a single CP subunit is an immunodominant epitope consisting of residues 169 to 180 [CP(169-180)], which is exposed on the surface of the subunit, but, in the structural context of the VLP, the epitope is buried and inaccessible to antibody. High levels of anti-CP(169-180) activity are associated with porcine circovirus-associated disease (PCVAD). The purpose of this study was to investigate the role of the immune response to monomer CP in the development of PCVAD. The approach was to immunize pigs with CP monomer, followed by challenge with PCV2 and porcine reproductive and respiratory syndrome virus (PRRSV). To maintain the CP immunogen as a stable monomer, CP(43-233) was fused to ubiquitin (Ub-CP). Size exclusion chromatography showed that Ub-CP was present as a single 33-kDa protein. Pigs immunized with Ub-CP developed a strong antibody response to PCV2, including antibodies against CP(169-180). However, only low levels of virus neutralizing activity were detected, and viremia levels were similar to those of nonimmunized pigs. As a positive control, immunization with baculovirus-expressed CP (Bac-CP) resulted in high levels of virus neutralizing activity, small amounts of anti-CP(169-180) activity, and the absence of viremia in pigs following virus challenge. The data support the role of CP(169-180) as an immunological decoy and illustrate the importance of the structural form of the CP immunogen in determining the outcome following infection.

Follicular expression of follicle stimulating hormone receptor variants in the ewe.

BACKGROUND: Several alternatively-spliced mRNA transcripts of the follicle stimulating hormone receptor (FSHR) have been identified in sheep, including FSHR-1 (G protein-coupled form), FSHR-2 (dominant negative form), and FSHR-3 (growth factor type-1 form). Our objective was to determine which of these variants is predominantly expressed in follicles collected from ewes at various times after estrus. METHODS: Suffolk-cross ewes (n = 8) were allowed to come into estrus naturally and were euthanized 24 (n = 3), 36 (n = 3), or 48 (n = 2) hours after the onset of estrus. All visible follicles were measured, aspirated and pooled according to follicular diameter: small (<= 2.0 mm), medium (2.1-4.0 mm), large (4.1-6.0 mm), and preovulatory (> = 6.1 mm). Aspirated cells were separated from follicular fluid by centrifugation. Total RNA was extracted from cell pellets and reverse transcribed. The resulting cDNA was subjected to qPCR, using primer sets designed to amplify each variant specifically. Gene expression was normalized to that of beta-actin within samples, and compared by analysis of variance with the level of significant differences set at p < .05. RESULTS: Relative expression of FSHR-3 exceeded that of both FSHR-1 and FSHR-2 in medium follicles, and tended to be higher in small follicles (p = .09) regardless of time after onset of estrus, and thus results from different time points were pooled. Expression of FSHR-3 was greater than that of FSHR-2 and luteinizing hormone receptor (LHR) in small and medium follicles. Expression of LHR was greatest in preovulatory follicles. CONCLUSIONS: These experiments show that in addition to the well characterized G protein-coupled form of the FSHR, alternatively spliced variants of the FSHR may participate in follicular dynamics during follicular waves of the sheep estrous cycle. Furthermore, these results indicate that an "alternatively" spliced form of the FSHR (FSHR-3) is the predominant form of the FSHR in the sheep.

First clinical results of adaptive radiotherapy based on 3D portal dosimetry for lung cancer patients with atelectasis treated with volumetric-modulated arc therapy (VMAT).

UNLABELLED: Atelectasis in lung cancer patients can change rapidly during a treatment course, which may displace the tumor/healthy tissues, or change tissue densities locally. This may result in differences between the planned and the actually delivered dose. With complex delivery techniques treatment verification is essential and inter-fractional adaptation may be necessary. We present the first clinical results of treatment adaptation based on an in-house developed three-dimensional (3D) portal dose measurement (PDM) system. MATERIAL AND METHODS: A method was developed for 3D PDM combined with cone beam computed tomography (kV-CBCT) imaging. Lung cancer patients are monitored routinely with this imaging technique. During treatment, the first three fractions are analyzed with 3D PDM and weekly thereafter. The reconstructed measured dose is compared to the planned dose using dose-volume histograms and a γ evaluation. Patients having |γ|> 1 in more than 5% of the (primary tumor or organ at risk) volume were subjected to further analysis. In this study we show the PDM dose changes for five patients. RESULTS: We detected relevant dose changes induced by changes in atelectasis in the presented cases. Two patients received two treatment adaptations after being detected with PDM confirmed by visual inspection of the kV-CBCTs, and in two other patients the radiation treatment plan was adapted once. In one case no dose delivery change was detected with PDM. CONCLUSION: The first clinical patients show that 3D PDM combined with kV-CBCT is a valuable quality assurance tool for detecting anatomical alterations and their dosimetric consequences during the course of radiotherapy. In our clinic, 3D PDM is fully automated for ease and speed of the procedure, and for minimization of human error. The technique is able to flag patients with suspected dose discrepancies for potential adaptation of the treatment plan.

Proactive pharmaceutical care interventions improve patients' adherence to lipid-lowering medication.

BACKGROUND: Lipid-lowering drugs are effective preventive medication for patients at risk of cardiovascular complications. However, medication adherence is suboptimal, thereby decreasing therapy effectiveness. Pharmaceutical care interventions may increase therapy adherence. OBJECTIVE: To assess the effect of a proactive pharmaceutical care intervention program, Medication Monitoring and Optimization (MeMO), on therapy discontinuation and adherence with lipid-lowering drugs as well as patients' satisfaction with the intervention program. METHODS: This prospective intervention study included 1002 patients initiating lipid-lowering drug therapy from 9 Dutch community pharmacies. In the intervention group (n = 500), the MeMO program was used, comprising continuous monitoring of patients' adherence to lipid-lowering drugs and personal counseling with nonadherent patients. The intervention group was compared with a historical reference group (n = 502) receiving usual care. Outcomes were therapy discontinuation and adherence. RESULTS: Discontinuation rates with lipid lowering drugs in the first year after drug initiation were 13.6% for the intervention group and 25.9% in the usual care group; continued but non-adherent use was 3.2% and 7.6% in these groups. Patients in the MeMO program had a decreased risk to discontinue medication of 51% (95% confidence interval: 34%-63%). Results were not affected by potential confounders. Patient satisfaction with MeMO was very high; one quarter of patients mentioned that they only received information about their medication from their pharmacy. CONCLUSIONS: Improving adherence to lipid lowering drugs can be achieved by a proactive pharmaceutical care program. Pharmacists can contribute to optimal use of chronic medication, which is likely to reduce healthcare costs.

A Local Desiccant Antimicrobial Agent as an Alternative to Adjunctive Antibiotics in the Treatment of Periodontitis: A Narrative Review.

Periodontitis is one of the most common oral polymicrobial infectious diseases induced by the complex interplay between the altered subgingival microbiota and the host's dysregulated immune-inflammatory response, leading to the initiation of progressive and irreversible destruction of the periodontal tissues and eventually to tooth loss. The main goal of cause-related periodontal therapy is to eliminate the dysbiotic subgingival biofilm in order to arrest local inflammation and further periodontal tissue breakdown. Because, in some cases, subgingival mechanical instrumentation has limited efficiency in achieving those goals, various adjunctive therapies, mainly systemic and locally delivered antimicrobials, have been proposed to augment its effectiveness. However, most adjunctive antimicrobials carry side effects; therefore, their administration should be precociously considered. HybenX® (HY) is a commercial therapeutical agent with decontamination properties, which has been studied for its effects in treating various oral pathological conditions, including periodontitis. This review covers the current evidence regarding the treatment outcomes and limitations of conventional periodontal therapies and provides information based on the available experimental and clinical studies related to the HY mechanism of action and effects following its use associated with subgingival instrumentation and other types of dental treatments.

Drinking water and the implications for gender equity and empowerment: A systematic review of qualitative and quantitative evidence.

BACKGROUND: Safe drinking water is a fundamental human right, yet more than 785 million people do not have access to it. The burden of water management disproportionately falls on women and young girls, and they suffer the health, psychosocial, political, educational, and economic effects. While water conditions and disease outcomes have been widely studied, few studies have summarized the research on drinking water and implications for gender equity and empowerment (GEE). METHODS: A systematic review of primary literature published between 1980 and 2019 was conducted on drinking water exposures and management and the implications for GEE. Ten databases were utilized (EMBASE, PubMed, Web of Science, Cochrane, ProQuest, Campbell, the British Library for Development Studies, SSRN, 3ie International Initiative for Impact Evaluation, and clinicaltrials.gov). Drinking water studies with an all-female cohort or disaggregated findings according to gender were included. RESULTS: A total of 1280 studies were included. GEE outcomes were summarized in five areas: health, psychosocial stress, political power and decision-making, social-educational conditions, and economic and time-use conditions. Water quality exposures and implications for women's health dominated the literature reviewed. Women experienced higher rates of bladder cancer when exposed to arsenic, trihalomethanes, and chlorine in drinking water and higher rates of breast cancer due to arsenic, trichloroethylene, and disinfection byproducts in drinking water, compared to men. Women that were exposed to arsenic experienced higher incidence rates of anemia and adverse pregnancy outcomes compared to those that were not exposed. Water-related skin diseases were associated with increased levels of psychosocial stress and social ostracization among women. Women had fewer decision-making responsibilities, economic independence, and employment opportunities around water compared to men. CONCLUSION: This systematic review confirms the interconnected nature of gender and WaSH outcomes. With growing attention directed towards gender equity and empowerment within WaSH, this analysis provides key insights to inform future research and policy.