Light regulation in critical human pathogens of clinical relevance such as Acinetobacter baumannii, Staphylococcus aureus and Pseudomonas aeruginosa.

It is now clearly recognized that light modulates the physiology of many bacterial chemotrophs, either directly or indirectly. An interesting case are bacterial pathogens of clinical relevance. This work summarizes, discusses, and provides novel complementary information to what is currently known about light sensing and responses in critical human pathogens such as Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus. These pathogens are associated with severe hospital and community infections difficult to treat due to resistance to multiple drugs. Moreover, light responses in Brucella abortus, an important animal and human pathogen, are also compiled. Evidence recovered so far indicates that light modulates aspects related to pathogenesis, persistence, and antibiotic susceptibility in these pathogens; such as motility, biofilm formation, iron uptake, tolerance to antibiotics, hemolysis and virulence. The pathogens elicit differential responses to light depending likely on their pathophysiology, ability to cause disease and characteristics of the host. The response to light is not restricted to discrete physiological traits but is global. In higher organisms, light provides spatial and temporal information. Then, it is crucial to understand what information light is providing in these bacterial pathogens. Our current hypothesis postulates that light serves as a signal that allows these pathogens to synchronize their behavior to the circadian rhythm of the host, to optimize infection. Advances on the molecular mechanism of light signal transduction and physiological responses to light, as well as in the relation between light and bacterial infection, would not only enlarge our understanding of bacterial pathogenesis but also could potentially provide alternative treatment options for infectious illnesses.

Genome Sequence of Clinical Acinetobacter baumannii Strain V15.

Acinetobacter baumannii is recognized as a critical human pathogen by the World Health Organization, and therefore there is increasing interest in studying its biology and pathophysiology. Among other strains, A. baumannii V15 has been extensively used for these purposes. Here, the genome sequence of A. baumannii V15 is presented.

BfmRS encodes a regulatory system involved in light signal transduction modulating motility and desiccation tolerance in the human pathogen Acinetobacter baumannii.

We have previously shown that Acinetobacter baumannii as well as other relevant clinical bacterial pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa, perceive and respond to light at 37 °C, the normal temperature in mammal hosts. In this work, we present evidence indicating that the two-component system BfmRS transduces a light signal in A. baumannii at this temperature, showing selective involvement of the BfmR and BfmS components depending on the specific cellular process. In fact, both BfmR and BfmS participate in modulation of motility by light, while only BfmR is involved in light regulation of desiccation tolerance in this microorganism. Neither BfmR nor BfmS contain a photoreceptor domain and then most likely, the system is sensing light indirectly. Intriguingly, this system inhibits blsA expression at 37 °C, suggesting antagonistic functioning of both signaling systems. Furthermore, we present evidence indicating that the phosphorylatable form of BfmR represses motility. Overall, we provide experimental evidence on a new biological function of this multifaceted system that broadens our understanding of A. baumannii's physiology and responses to light.

Characterization of BLUF-photoreceptors present in Acinetobacter nosocomialis.

Acinetobacter nosocomialis is a Gram-negative opportunistic pathogen, whose ability to cause disease in humans is well recognized. Blue light has been shown to modulate important physiological traits related to persistence and virulence in this microorganism. In this work, we characterized the three Blue Light sensing Using FAD (BLUF) domain-containing proteins encoded in the A. nosocomialis genome, which account for the only canonical light sensors present in this microorganism. By focusing on a light-modulated bacterial process such as motility, the temperature dependence of light regulation was studied, as well as the expression pattern and spectroscopic characteristics of the different A. nosocomialis BLUFs. Our results show that the BLUF-containing proteins AnBLUF65 and AnBLUF46 encode active photoreceptors in the light-regulatory temperature range when expressed recombinantly. In fact, AnBLUF65 is an active photoreceptor in the temperature range from 15°C to 37°C, while AnBLUF46 between 15°C to 32°C, in vitro. In vivo, only the Acinetobacter baumannii BlsA's ortholog AnBLUF65 was expressed in A. nosocomialis cells recovered from motility plates. Moreover, complementation assays showed that AnBLUF65 is able to mediate light regulation of motility in A. baumannii ΔblsA strain at 30°C, confirming its role as photoreceptor and in modulation of motility by light. Intra-protein interactions analyzed using 3D models built based on A. baumannii´s BlsA photoreceptor, show that hydrophobic/aromatic intra-protein interactions may contribute to the stability of dark/light- adapted states of the studied proteins, reinforcing the previous notion on the importance of these interactions in BLUF photoreceptors. Overall, the results presented here reveal the presence of BLUF photoreceptors in A. nosocomialis with idiosyncratic characteristics respect to the previously characterized A. baumannii's BlsA, both regarding the photoactivity temperature-dependency as well as expression patterns, contributing thus to broaden our knowledge on the BLUF family.

Resistance to platinum-based cancer drugs: a special focus on epigenetic mechanisms.

Chemoresistance is a significant clinical challenge, limiting the drug response in cancer. Several mechanisms associated with drug resistance have been characterized, and the role of epigenetics in generating resistance to platinum-based drugs has been clarified. Epigenetic mechanisms such as DNA methylation, histone modification, long noncoding RNA, and microRNA affect the expression of genes implicated in absorption, distribution, metabolism and excretion (ADME) of drugs, and other non-ADME genes that encode enzymes involved in the processes of cell proliferation, DNA repair, apoptosis and signal transduction key in the development of chemoresistance in cancer, specifically in platinum-based drugs. This review summarizes current discoveries in epigenetic regulation implicated in platinum drug resistance in cancer and the main clinical trials based on epigenetic therapy, evaluating their potential synergy with platinum-based drugs.

Phylogenetic dating analysis of HTLV-1 from Chile suggests transmissions events related to ancient migrations and contemporary expansion.

Human T-cell lymphotropic virus type 1 (HTLV-1) is a globally-spread virus. It is estimated that there are about 5­10 million infected people in the world. HTLV is endemic in Chile, with higher seroprevalence among indigenous people. However, little is known about HTLV-1 genetic diversity, its introduction and dispersion in this country. To gain insights into these issues, a phylogenetic dating analysis was conducted based on Chilean and closed related long terminal repeat sequences. The time tree reconstruction showed that the introduction of HTLV-1aA occurred several times in Chile. It was hypothesized that these introductions took place at least in two different historical moments: (i) during the ancient human migrations and (ii) during/after the European colonization of South America. The present study contributes toward understanding the evolutionary history of HTLV-1 in Chile and South America.

Comprehensive treatment in severe dengue during preterm and term labor: could tocolysis be useful?

Objective: There is lack of data on the management of severe dengue infection during labor. The objective of this study was to describe our experience in the management of preterm and term labor of pregnant patients with severe dengue infection and thrombocytopenia.Materials and methods: We describe patients with dengue infection confirmed by dengue serology or NS1 antigen in Cali, Colombia. All of the patients had warning or severity signs for dengue and initiated labor, either term or preterm, during their hospital stay. All had thrombocytopenia at the moment labor started. Therefore, we treated them with support management, including intravenous fluids and a tocolytic agent (either atosiban, magnesium sulfate or nifedipine). Tocolytics aimed to stop contractions until platelets were in a safe range previous to delivery. Platelets transfusions were performed if the count was less than 10,000 cells/ml and active bleeding was present. The primary outcome we evaluated was postpartum hemorrhage (defined as a loss of >500 ml following a vaginal delivery or >1000 ml after cesarean section) or maternal and neonatal morbidity and mortality.Results: We present a total of six pregnant women. The median platelet count 24 h previous to delivery was 94,000 cells/ml and after tocolysis was 132,500 cells/ml. Two patients suffered postpartum hemorrhage despite the management. Only one woman required platelet transfusion. No maternal or newborn mortality were present. Three patients were diagnosed with preeclampsia. Four patients had delivery via cesarean section. Five out of six newborns required hospitalization, three of them due to neonatal respiratory distress syndrome.Conclusion: Comprehensive treatment including fluids resuscitation and uterine inhibition in pregnant women with severe dengue in preterm or term labor could be useful. More clinical studies are required to evaluate the benefit of this intervention in tropical countries.Brief rationale: We present an original research article and literature review entitled "Comprehensive treatment in severe dengue during preterm and term labor: could tocolysis be useful?". Our article describes the clinical manifestation, laboratory findings, complications and management provided to a group of six patients that presented to the hospital with acute dengue virus infection and initiated labor while viremic and thrombocytopenic in this study.In the present study, we found that most of our patients (5 out of 6), presented with signs of severe dengue fever and all of the patients had warning signs. In this population, we decided to provide support treatment and tocolytic agents to these patients with the aim of delaying labor to allow platelet count to rise, thus reducing the odds of hemorrhagic complications. We concluded that although tocolysis is not regularly used in patients with dengue fever, our results suggest that our protocol could benefit pregnant patients with thrombocytopenia due to dengue; however, prospective studies which determine the safety and effectiveness of our intervention are needed.

A scoping review of transmission of dengue virus from donors to recipients after solid organ transplantation.

Dengue virus can infect humans through vectorial and non-vectorial transmission. Classically, non-vectorial transmission has been related to vertical transmission and health care-associated infections, but recently transmission to solid organ and bone marrow recipients has been reported. We performed a scoping review of the available literature searching for evidence on screening for dengue in potential organ donors and the use of these infected organs. From 372 unique records identified, 17 were eligible to be included in our scoping study. After applying inclusion and exclusion criteria, three studies were included. These studies described a total of six patients from India (two case reports; n=2) and Colombia (one case series; n=4). Three patients received a liver, two received a kidney and one had a heart transplant. The onset of symptoms occurred in the first week after transplant in all cases and all experienced fever as the primary symptom. All patients presented thrombocytopenia with a platelet count <50 000. None of the patients developed graft rejection. However, four patients presented graft complications. No recipient deaths occurred. There is not a strong recommendation for dengue screening of donors in transplantation guidelines, but in endemic areas, physicians should be aware of this type of transmission before transplantation.

Ileostomía y lavado colónico anterógrado con Vancomicina en el manejo de infección por Clostridium difficile / Anterograde colonic lavage with Vancomycin via ileostomy for the management of Clostridium difficile infection. A case report

La infección por Clostridium difficile es la principal causa de diarrea asociada al cuidado de la salud. Durante los últimos años se ha incrementado la morbilidad y mortalidad por esta infección. Las recientes investigaciones se orientan a la búsqueda de tratamientos alternativos a la colectomía subtotal para los pacientes con infecciones severas por Clostridium difficile, es por esto que el presente artículo tiene como objetivo hacer la revisión del caso clínico de una paciente con colitis severa por Clostridium difficile refractaria al manejo de primera línea, que respondió satisfactoriamente al tratamiento con lavado colónico anterógrado con vancomicina vía ileostomía en asa.

Clostridium difficile infection is the main cause of diarrhea in health care settings. Such infections have led to an increase in morbidity and mortality in recent years. Alternative treatments to subtotal colectomy have been sought for patients with severe infections caused by Clostridium difficile. The objective of this article is to present a clinical case report of a patient with severe colitis caused by Clostridium difficile that was refractory to first-line management, which responded satisfac torily to treatment with anterograde colonic lavages with vancomycin via loop ileostomy.

Invasive fungal infection by Aspergillus flavus in immunocompetent hosts: A case series and literature review.

Invasive aspergillosis usually affects immunocompromised hosts with variable manifestations depending on the site of infection. In this article, we present two cases of invasive Aspergillosis in two non-immunocompromised patients; both cases had a paranasal sinuses infection, with intraorbital and intracranial extension, requiring surgery and antifungal treatment with Voriconazole. These cases were initially diagnosed as paranasal sinus neoplasms. However, the pathology and microbiology studies revealed invasive fungal infection by Aspergillus flavus.

Chikungunya in solid organ transplant recipients, a case series and literature review.

Chikungunya virus is a recent emerging arbovirus in Latin America, and the clinical manifestations can vary from fever and rash to severe chronic inflammatory arthritis. Few reports have been published regarding this infection in immunocompromised patients, including solid organ transplant recipients. We report a case series of solid organ transplant recipients with confirmed Chikungunya infection by positive reverse transcription polymerase chain reaction (RT-PCR), identified between January 2014 and December 2016. In addition, we conducted a literature review searching PubMed, EMBASE, and LILACS databases on Chikungunya infection in solid organ transplant recipients. Ten solid organ transplant recipients were included, consisting of 5 kidney, 4 liver, and 1 liver/kidney transplant recipient. Mean age of the transplant recipients was 47 years, and the most frequent symptoms of Chikungunya infection were arthralgia and fever. None of the patients required treatment in the intensive care unit, no deaths or graft rejection occurred. None of our patients had recurrent arthritis during 3-month follow-up period after the infection. Twenty-one cases of Chikungunya virus were identified in the literature review. Most cases had a benign clinical course with no severe complications, death, or chronic inflammatory arthritis. In conclusion, Chikungunya infection in solid organ transplant recipients has a benign course and has no chronic recurrent arthritis. It is possible that the immunosuppression regimen could decrease the risk of severe or chronic inflammatory manifestations in solid organ transplant recipients infected with Chikungunya.

Aportes a la seguridad alimentaria a través de la lactancia materna en comunidades rurales / Contributions to food security through breastfeeding in rural communities

Desde el 2008 Colombia aprueba la Política Nacional de Seguridad Alimentaria y Nutricional, esta recomienda la lactancia materna (LM) por los beneficios en el bienestar de la familia y el niño, al prevenir infecciones respiratorias, digestivas, neurológicas y por sus características nutricionales que contribuyen a un adecuado desarrollo neurológico, ganancia de talla y peso, este estudio evaluó esta práctica en población rural. Métodos Mediante grupos focales, 25 personas convocadas por escuelas campesinas de agroecología intercambiaron prácticas y saberes sobre LM, las entrevistadas corresponden a la generación actual y la anterior que tuvieron experiencias de LM. Resultados La generación más joven con paridad entre 1 y 5, lactó en promedio 14.9 meses y las abuelas con paridad entre 1 y 12, lactó en promedio 22 meses. La leche entera de vaca se aprecia tanto como la leche humana, esta es valorada por sus efectos en el desarrollo y bienestar de los hijos, siendo más alegres y activos, más no reconocen sus beneficios económicos. Consideran que genera alteraciones físicas en las madres y en la sexualidad de los varoncitos. Conclusiones Disminuyó en 7 meses el promedio de duración de la LM entre las dos generaciones de madres. El desarrollo motor precoz y las expresiones de sexualidad observadas en los hijos, durante el acto de amamantamiento, motivaron a algunas madres a suspenderla antes de los 2 años de edad, igualmente los cambios anatómicos que afectan sicológica y estéticamente a las madres. Los participantes no valoran económica ni socialmente la LM.

Since 2008, Colombia has approved the National Food and Nutrition Security Policy, which recommends breastfeeding for welfare benefits of the family and child, and preventing respiratory, digestive, neurological infections and their contributing nutritional characteristics-Methods Through focus groups, 25 people convened by schools of agroecology exchanged practices and knowledge about breastfeeding, the interviewees correspond to the current and previous generations who practiced breastfeeding. Results The youngest generation with parity between 1 and 5, had breastfeeding mean 14.9 months and grandmothers had parity between 1 and 12, lactated on average 22 months. All them were thinking Whole cow’s milk is good as human milk. Breastfeeding was valued for its effects on the development and well-being of children, their children being more cheerful and active, but they do not recognize their economic benefits in breastfeeding vs cow’s milk. The mothers consider that breastfeeding generates physical alterations in the mothers and in the sexuality of the children Conclusions Breastfeeding decreased in seven months between the two generations. The early motor development and the expressions of sexuality observed in the children, during breastfeeding, motivated some mothers to suspend before the 2 years of age, also the anatomical changes perceiving for mothers was defined cause for interrupt breastfeeding .

Frecuencia de virus papiloma humano en tumores no ginecológicos de la Región de la Araucanía, Chile / Human papilloma virus frequency in non-gynecological tumors in the Araucanía Region, Chile

El Virus Papiloma Humano (HPV por sus siglas en inglés) es una de las infecciones de transmisión sexual más frecuentes del mundo y se encuentra presente en la mayoría de los cánceres de cuello uterino. Se ha descrito su presencia en otros tipos de cáncer no ginecológicos como lo son esófago y próstata. Sin embargo, las frecuencias de HPV descritas hasta el momento para estos tipos de cáncer son muy variables, y no hay artículos donde se muestren la presencia de HPV en estas neoplasias en Chile. El objetivo de este estudio fue determinar la frecuencia de HPV en muestras de biopsias de tumores no ginecológicos y tejido inflamatorio de pacientes de la región de La Araucanía. Se extrajo DNA desde un total de 47 biopsias de pacientes con esofagitis, 25 con carcinoma escamoso esofágico, 20 con hiperplasia nodular de la próstata y 39 con adenocarcinoma prostático. Estas fueron analizadas por PCR de la región L1 del virus y posterior genotipificación por reverse line blot. Se detectó HPV en el 53,2% de las muestras de esofagitis, 48% en muestras de carcinoma escamoso esofágico, 15% en hiperplasia nodular de la próstata y un 15,4% en los casos de adenocarcinoma prostático. Siendo los más frecuentes los genotipos de HPV 16 y 18, ya sea en infecciones simples o junto con otros genotipos, en lesiones preneoplásicas y neoplásicas de los tejidos estudiados. Existe una alta frecuencia de infección por HPV en biopsias de esofagitis y tejido inflamatorio esofágico de pacientes de la región de la Araucanía. En los casos de adenocarcinoma prostático e hiperplasia nodular de la próstata se observa una baja frecuencia de HPV.

Human Papilloma Virus (HPV) is the most common sexually transmitted disease in the world and it is present in practically all cervical cancers. Its presence was described in other types of non-gynecologic cancer such as esophageal and prostate. However, HPV frequency described for these cancers is highly variable, and there are no articles describing the presence of HPV in these tumors in Chile. To determine HPV frequency in samples from biopsies of non-gynecological tumors and inflammatory tissue from patients in the Araucanía region, DNA was extracted from a total of 47 biopsies from patients with esophagitis, 25 with esophageal squamous cell carcinoma, 20 with prostate nodular hyperplasia and 39 with prostate adenocarcinoma. These were analyzed by PCR of HPV L1 region and subsequent genotyping by reverse line blot. HPV was detected in 53.2% of esophagitis samples, 48% in esophageal squamous cell carcinoma, 15% in prostatitis and 15.4% in cases of prostatic adenocarcinoma. The most frequent HPV genotypes were 16 and 18, either single or in combination with other genotype infections, in inflammatory tissue and neoplastic lesions. In patients of the Araucanía region, there is a high rate of HPV infection in biopsies obtained in esophagitis and esophageal inflammatory tissue. In cases of prostatic adenocarcinoma and prostate nodular hyperplasia a low rate of HPV was observed.