Modulation of the Tumor Microenvironment by Microbiota-Derived Short-Chain Fatty Acids: Impact in Colorectal Cancer Therapy.

Finding new therapeutic approaches towards colorectal cancer (CRC) is of increased relevance, as CRC is one of the most common cancers worldwide. CRC standard therapy includes surgery, chemotherapy, and radiotherapy, which may be used alone or in combination. The reported side effects and acquired resistance associated with these strategies lead to an increasing need to search for new therapies with better efficacy and less toxicity. Several studies have demonstrated the antitumorigenic properties of microbiota-derived short-chain fatty acids (SCFAs). The tumor microenvironment is composed by non-cellular components, microbiota, and a great diversity of cells, such as immune cells. The influence of SCFAs on the different constituents of the tumor microenvironment is an important issue that should be taken into consideration, and to the best of our knowledge there is a lack of reviews on this subject. The tumor microenvironment is not only closely related to the growth and development of CRC but also affects the treatment and prognosis of the patients. Immunotherapy has emerged as a new hope, but, in CRC, it was found that only a small percentage of patients benefit from this treatment being closely dependent on the genetic background of the tumors. The aim of this review was to perform an up-to-date critical literature review on current knowledge regarding the effects of microbiota-derived SCFAs in the tumor microenvironment, particularly in the context of CRC and its impact in CRC therapeutic strategies. SCFAs, namely acetate, butyrate, and propionate, have the ability to modulate the tumor microenvironment in distinct ways. SCFAs promote immune cell differentiation, downregulate the expression of pro-inflammatory mediators, and restrict the tumor-induced angiogenesis. SCFAs also sustain the integrity of basement membranes and modulate the intestinal pH. CRC patients have lower concentrations of SCFAs than healthy individuals. Increasing the production of SCFAs through the manipulation of the gut microbiota could constitute an important therapeutic strategy towards CRC due to their antitumorigenic effect and ability of modulating tumor microenvironment.

Patients' Perspectives on Determinants Avoidable Hospitalizations: Development and Validation of a Questionnaire.

Ambulatory care sensitive conditions (ACSC) can be avoided through effective care in the ambulatory setting. Patients are the most qualified individuals to express the social and individual contexts of their own experience. Thus, understanding why potentially preventable hospitalizations occur is important to develop patient-centred policies or interventions that may reduce them. This study aims to develop and validate a questionnaire to capture the patients' perspective on the causes of the hospitalizations for ACSC. The development of a new questionnaire involved four phases: a literature review, face validity, pre-test, and validation. We conducted a three-step face validity verification to confirm the relevance of the identified determinants and to collect determinants not previously identified by interviewing healthcare providers, representatives of patients' associations, and patients. Determinants were identified through the literature review predominantly in the "Healthcare Access", "Disease self-management", and "Social Support" domains. The validated resulting questionnaire comprises 25 questions, distributed by two dimensions (individual/contextual) covering seven domains and 20 determinants of ACSC hospitalization. Currently, there are no validated instruments as comprehensive and easy to use as the one described in this paper. This questionnaire should provide a base for further language/context validations.

Risk Factors for Nasal Colonization by Methicillin-Resistant Staphylococci in Healthy Humans in Professional Daily Contact with Companion Animals in Portugal.

Methicillin-resistant staphylococci (MRS), namely Staphylococcus aureus (MRSA) and Staphylococcus pseudintermedius (MRSP), are opportunistic agents of great importance in human and veterinary medicine. The aims of this study were to investigate the frequency, persistence, and risk factors associated with nasal colonization by MRS in people in daily contact with animals in Portugal. Seventy-nine out of 129 (61.2%) participants were found to be colonized by, at least, one methicillin-resistant (MR) staphylococci species (MR Staphylococcus epidermidis [n = 68], MRSA [n = 19], MR Staphylococcus haemolyticus [n = 7], MRSP [n = 2], and other coagulase-negative staphylococci [n = 4]). Three lineages were identified among the MRSA isolates (n = 7): the major human healthcare clone in Portugal (ST22-t032-IV, n = 3), the livestock-associated MRSA (ST398-t108-V, n = 3), and the New York-/Japan-related clone (ST105-t002-II, n = 1). MRSP isolates belonged to the European clone ST71-II-III. We identified two risk factors for nasal colonization by MRS in healthy humans: (i) being a veterinary professional (veterinarian and veterinary nurse) (p < 0.0001, odds ratio [OR] = 6.369, 95% confidence interval [CI, 2.683-15.122]) and (ii) have contacted with one MRSA- or MRSP-positive animal (p = 0.0361, OR = 2.742, 95% CI [1.067-7.045]). The follow-up study revealed that the majority (85%) remain colonized. This study shows that MRS in veterinary clinical practice is a professional hazard and highlights the need to implement preventive measures to minimize spread.

Hand, foot, and mouth syndrome in an immunocompetent adult: a case report.

BACKGROUND: Hand, foot, and mouth syndrome (HFMS) is a common acute illness. It is characterized by mild clinical symptoms including fever, blisters, and sores in the mouth and on the palms and soles following a 3- to 7-day incubation period. This syndrome is rarely seen in adults. CASE PRESENTATION: A 35-year-old male Caucasian patient had a history of multiple episodes of acute pharyngitis, hypertension, hypercholesterolemia, and occasional abdominal pain. He presented with polyarthralgia in the knees and hands and odynophagia, followed by fever, oral mucosal aphthous lesions, and vesicles on the palms and soles. Three weeks after presentation, he was admitted to the emergency room with acute myocarditis. The in-hospital evaluation revealed positive serology for coxsackie A9 (1:160), positive anti-transglutaminase and anti-gliadin antibodies, normal immunoglobulins, and human immunodeficiency virus negativity. CONCLUSION: We herein describe a case of HFMS that was associated with coxsackie A9 infection complicated by acute myocarditis. Although an association between celiac disease and HFMS has not been described, this patient's immunologic disruption could have favored the development of infection and ultimately HFMS.