Lactated Ringers Use in the First 24 Hours of Hospitalization Is Associated With Improved Outcomes in 999 Patients With Acute Pancreatitis.

INTRODUCTION: Recent pilot trials in acute pancreatitis (AP) found that lactated ringers (LR) usage may result in decreased risk of moderately severe/severe AP compared with normal saline, but their small sample sizes limit statistical power. We investigated whether LR usage is associated with improved outcomes in AP in an international multicenter prospective study. METHODS: Patients directly admitted with the diagnosis of AP were prospectively enrolled at 22 international sites between 2015 and 2018. Demographics, fluid administration, and AP severity data were collected in a standardized prospective manner to examine the association between LR and AP severity outcomes. Mixed-effects logistic regression analysis was performed to determine the direction and magnitude of the relationship between the type of fluid administered during the first 24 hours and the development of moderately severe/severe AP. RESULTS: Data from 999 patients were analyzed (mean age 51 years, female 52%, moderately severe/severe AP 24%). Usage of LR during the first 24 hours was associated with reduced odds of moderately severe/severe AP (adjusted odds ratio 0.52; P = 0.014) compared with normal saline after adjusting for region of enrollment, etiology, body mass index, and fluid volume and accounting for the variation across centers. Similar results were observed in sensitivity analyses eliminating the effects of admission organ failure, etiology, and excessive total fluid volume. DISCUSSION: LR administration in the first 24 hours of hospitalization was associated with improved AP severity. A large-scale randomized clinical trial is needed to confirm these findings.

The bioengineered and multifunctional nanoparticles in pancreatic cancer therapy: Bioresponisive nanostructures, phototherapy and targeted drug delivery.

The multidisciplinary approaches in treatment of cancer appear to be essential in term of bringing benefits of several disciplines and their coordination in tumor elimination. Because of the biological and malignant features of cancer cells, they have ability of developing resistance to conventional therapies such as chemo- and radio-therapy. Pancreatic cancer (PC) is a malignant disease of gastrointestinal tract in which chemotherapy and radiotherapy are main tools in its treatment, and recently, nanocarriers have been emerged as promising structures in its therapy. The bioresponsive nanocarriers are able to respond to pH and redox, among others, in targeted delivery of cargo for specific treatment of PC. The loading drugs on the nanoparticles that can be synthetic or natural compounds, can help in more reduction in progression of PC through enhancing their intracellular accumulation in cancer cells. The encapsulation of genes in the nanoparticles can protect against degradation and promotes intracellular accumulation in tumor suppression. A new kind of therapy for cancer is phototherapy in which nanoparticles can stimulate both photothermal therapy and photodynamic therapy through hyperthermia and ROS overgeneration to trigger cell death in PC. Therefore, synergistic therapy of phototherapy with chemotherapy is performed in accelerating tumor suppression. One of the important functions of nanotechnology is selective targeting of PC cells in reducing side effects on normal cells. The nanostructures are capable of being surface functionalized with aptamers, proteins and antibodies to specifically target PC cells in suppressing their progression. Therefore, a specific therapy for PC is provided and future implications for diagnosis of PC is suggested.

Epidemiology-driven approaches to surveillance in HPAI-vaccinated poultry flocks aiming to demonstrate freedom from circulating HPAIV.

Incursion pressure of high pathogenicity avian influenza viruses (HPAIV) by secondary spread among poultry holdings and/or from infected migratory wild bird populations increases worldwide. Vaccination as an additional layer of protection of poultry holdings using appropriately matched vaccines aims at reducing clinical sequelae of HPAIV infection, disrupting HPAIV transmission, curtailing economic losses and animal welfare problems and cutting exposure risks of zoonotic HPAIV at the avian-human interface. Products derived from HPAIV-vaccinated poultry should not impose any risk of virus spread or exposure. Vaccination can be carried out with zero-tolerance for infection in vaccinated herds and must then be flanked by appropriate surveillance which requires tailoring at several levels: (i) Controlling appropriate vaccination coverage and adequate population immunity in individual flocks and across vaccinated populations; (ii) assessing HPAI-infection trends in unvaccinated and vaccinated parts of the poultry population to provide early detection of new/re-emerged HPAIV outbreaks; and (iii) proving absence of HPAIV circulation in vaccinated flocks ideally by real time-monitoring. Surveillance strategies, i.e. selecting targets, tools and random sample sizes, must be accommodated to the specific epidemiologic and socio-economic background. Methodological approaches and practical examples from three countries or territories applying AI vaccination under different circumstances are reviewed here.

The Role of Polymorphisms at the Interleukin-1, Interleukin-4, GATA-3 and Cyclooxygenase-2 Genes in Non-Surgical Periodontal Therapy.

Periodontitis is a multifactorial disease. The aim of this explorative study was to investigate the role of Interleukin-(IL)-1, IL-4, GATA-3 and Cyclooxygenase-(COX)-2 polymorphisms after non-surgical periodontal therapy with adjunctive systemic antibiotics (amoxicillin/metronidazole) and subsequent maintenance in a Caucasian population. Analyses were performed using blood samples from periodontitis patients of a multi-center trial (ClinicalTrials.gov NCT00707369=ABPARO-study). Polymorphisms were analyzed using quantitative real-time PCR. Clinical attachment levels (CAL), percentage of sites showing further attachment loss (PSAL) ≥1.3 mm, bleeding on probing (BOP) and plaque score were assessed. Exploratory statistical analysis was performed. A total of 209 samples were genotyped. Patients carrying heterozygous genotypes and single-nucleotide-polymorphisms (SNP) on the GATA-3-IVS4 +1468 gene locus showed less CAL loss than patients carrying wild type. Heterozygous genotypes and SNPs on the IL-1A-889, IL-1B +3954, IL-4-34, IL-4-590, GATA-3-IVS4 +1468 and COX-2-1195 gene loci did not influence CAL. In multivariate analysis, CAL was lower in patients carrying GATA-3 heterozygous genotypes and SNPs than those carrying wild-types. For the first time, effects of different genotypes were analyzed in periodontitis progression after periodontal therapy and during supportive treatment using systemic antibiotics demonstrating a slight association of GATA-3 gene locus with CAL. This result suggests that GATA-3 genotypes are a contributory but non-essential risk factor for periodontal disease progression.

Distinct Effects of Milk-Derived and Fermented Dairy Protein on Gut Microbiota and Cardiometabolic Markers in Diet-Induced Obese Mice.

BACKGROUND: Recent meta-analyses suggest that the consumption of fermented dairy products reduces type 2 diabetes and cardiovascular disease (CVD) risk, although the underlying mechanisms remain unclear. OBJECTIVE: We evaluated whether dairy protein products modulated gut microbiota and cardiometabolic features in mouse models of diet-induced obesity and CVD. METHODS: Eight-week-old C57BL/6J wild-type (WT) and LDLr-/-ApoB100/100 (LRKO) male mice were fed for 12 and 24 wk, respectively, with a high-fat/high-sucrose diet [66% kcal lipids, 22% kcal carbohydrates (100% sucrose), 12% kcal proteins]. The protein sources of the 4 diets were 100% nondairy protein (NDP), or 50% of the NDP energy replaced by milk (MP), milk fermented by Lactobacillus helveticus (FMP), or Greek-style yogurt (YP) protein. Fecal 16S rRNA gene-based amplicon sequencing, intestinal gene expression, and glucose tolerance test were conducted. Hepatic inflammation and circulating adhesion molecules were measured by multiplex assays. RESULTS: Feeding WT mice for 12 wk led to a 74% increase in body weight, whereas after 24 wk the LRKO mice had a 101.5% increase compared with initial body weight. Compared with NDP and MP, the consumption of FMP and YP modulated the gut microbiota composition in a similar clustering pattern, upregulating the Streptococcus genus in both genotypes. In WT mice, feeding YP compared with NDP increased the expression of genes involved in jejunal (Reg3b, 7.3-fold, P = 0.049) and ileal (Ocln, 1.7-fold, P = 0.047; Il1-ß,1.7-fold, P = 0.038; Nos2, 3.8-fold, P = 0.018) immunity and integrity. In LRKO mice, feeding YP compared with MP improved insulin sensitivity by 65% (P = 0.039). In LRKO mice, feeding with FMP versus NDP attenuated hepatic inflammation (monocyte chemoattractant protein 1, 2.1-fold, P ˂ 0.0001; IL1-ß, 5.7-fold, P = 0.0003; INF-γ, 1.7-fold, P = 0.002) whereas both FMP [vascular adhesion molecule 1 (VCAM1), 1.3-fold, P = 0.0003] and YP (VCAM1, 1.04-fold, P = 0.013; intracellular adhesion molecule 1, 1.4-fold, P = 0.028) decreased circulating adhesion molecules. CONCLUSION: Both fermented dairy protein products reduce cardiometabolic risk factors in diet-induced obese mice, possibly by modulating the gut microbiota.

Adverse Childhood Experiences and Obesity Among Young Children with Neurodevelopmental Delays.

OBJECTIVES: Very little research has explored the complex relation between ACEs, poverty, and obesity in young children with neurodevelopmental delays. The purpose of this study was to examine whether ACEs predicted overweight/obesity in young children with neurodevelopmental delays after income was taken into account, and to examine the extent to which poverty moderated the relation between ACEs and overweight/obesity. METHODS: Participants were 180 children between the ages of 2 and 7 who were referred for a developmental and behavioral pediatrics evaluation (mean age 4.5 years old; 76% male) in the northeast United States. Parents completed a survey about their child's ACEs, and an electronic health record review was conducted. RESULTS: ACEs did not directly predict obesity after income was taken into account. However, poverty moderated the relation between ACEs and obesity, such that when children experienced no ACEs, there was no difference in the rates of obesity between children above and below the poverty threshold. Among children who did experience ACEs, children who also lived in poverty had higher rates of obesity than children who did not live in poverty. CONCLUSIONS FOR PRACTICE: Children with neurodevelopmental delays are at greater risk for overweight/obesity if they experience both risk factors of being in poverty and of experiencing ACEs. When conducting screenings, providers should understand that the impact of ACEs may vary by contextual factors such as poverty. More research is needed to identify factors that can mitigate the impact of poverty and ACEs on children's physical health.

[Adaptation to the reality of Latin America of the NASPGHAN/ESPGHAN 2016 Guidelines on the Diagnosis, Prevention and Treatment of Helicobacter pylori Infection in Pediatrics]. / Adaptación a la realidad de Latinoamérica de la Guía Clínica NASPGHAN/ESPGHAN 2016 sobre Diagnóstico, Prevención y Tratamiento de Infección por Helicobacter pylori en Pediatría.

INTRODUCTION: The latest joint H. pylori NASPGHAN and ESPGHAN clinical guidelines published in 2016, contain 20 statements that have been questioned in practice regarding their applicability in Latin America (LA); in particular in relation to gastric cancer prevention. METHODS: We conduc ted a critical analysis of the literature, with special emphasis on LA data and established the level of evidence and level of recommendation of the most controversial claims in the Joint Guidelines. Two rounds of voting were conducted according to the Delphi consensus technique and a Likert scale (from 0 to 4) was used to establish the "degree of agreement" among a panel of SLAGHNP ex perts. RESULTS: There are few studies regarding diagnosis, treatment effectiveness and susceptibility to antibiotics of H. pylori in pediatric patients of LA. Based on these studies, extrapolations from adult studies, and the clinical experience of the participating expert panel, the following recom mendations are made. We recommend taking biopsies for rapid urease and histology testing (and samples for culture or molecular techniques, when available) during upper endoscopy only if in case of confirmed H. pylori infection, eradication treatment will be indicated. We recommend that selected regional centers conduct antimicrobial sensitivity/resistance studies for H. pylori and thus act as reference centers for all LA. In case of failure to eradicate H. pylori with first-line treatment, we recommend empirical treatment with quadruple therapy with proton pump inhibitor, amoxi cillin, metronidazole, and bismuth for 14 days. In case of eradication failure with the second line scheme, it is recommended to indicate an individualized treatment considering the age of the pa tient, the previously indicated scheme and the antibiotic sensitivity of the strain, which implies performing a new endoscopy with sample extraction for culture and antibiogram or molecular resistance study. In symptomatic children referred to endoscopy who have a history of first or se cond degree family members with gastric cancer, it is recommended to consider the search for H. pylori by direct technique during endoscopy (and eradicate it when detected). CONCLUSIONS: The evidence supports most of the general concepts of the NASPGHAN/ESPGHAN 2016 Guidelines, but it is necessary to adapt them to the reality of LA, with emphasis on the development of regional centers for the study of antibiotic sensitivity and to improve the correct selection of the eradication treatment. In symptomatic children with a family history of first or second degree gastric cancer, the search for and eradication of H. pylori should be considered.

Health need assessment in an indigenous high-altitude population living on an island in Lake Titicaca, Perú.

BACKGROUND: Health needs and access to health care is a huge challenge in developing countries, especially in some isolated indigenous communities. Amantani is an island located at 3854 m above sea level in Lake Titicaca, Peru. There is no official date on key local health needs and determinants, which precludes the prioritization and efficient implementation of health interventions. The objective of this study is to validate a health need assessment tool and ascertain the main health needs of the indigenous high-altitude population living on Amantani. METHODS: We conducted a cross-sectional study to describe the health needs of the indigenous population of Amantani using a questionnaire based on the "Peruvian Demographic and Health Survey". The questionnaire underwent expert and field-work validation. We selected a random sample of the island residents using two-stage cluster sampling. We estimated the prevalence of key health needs and determinants, and evaluated their distribution by age, sex and education through prevalence ratio. All analyses accounted for the complex sampling design. RESULTS: We surveyed 337 individuals (223 adults and 144 children) in 151 houses. The most frequent health needs were: (i) lack of access to medical screening for a)non-communicable diseases (> 63.0%) and b)eye problems (76.5%); and (ii) poor knowledge about communicable diseases (> 54.3%), cancer (71.4%) and contraception (> 32.9%). Smoking and alcohol use was more frequent in males (PR = 4.70 IC95%:1.41-15.63 and PR = 1.69 95% CI:1.27-2.25, respectively). People with higher education had more knowledge about TB/HIV and cancer prevention (p < 0.05). Regarding children's health, > 38% have never undergone eye or dental examination. Corporal punishment and physical bullying at school in the last month were relatively common (23 and 33%, respectively). CONCLUSION: The main health needs in Amantani are related to poor healthcare access and lack of awareness of disease prevention. Our findings can be used to develop and implement efficient health interventions to improve the health and quality of life of indigenous populations living in the islands in Southern Peru/Northern Bolivia.

Tau reduction in the presence of amyloid-ß prevents tau pathology and neuronal death in vivo.

Several studies have now supported the use of a tau lowering agent as a possible therapy in the treatment of tauopathy disorders, including Alzheimer's disease. In human Alzheimer's disease, however, concurrent amyloid-ß deposition appears to synergize and accelerate tau pathological changes. Thus far, tau reduction strategies that have been tested in vivo have been examined in the setting of tau pathology without confounding amyloid-ß deposition. To determine whether reducing total human tau expression in a transgenic model where there is concurrent amyloid-ß plaque formation can still reduce tau pathology and protect against neuronal loss, we have taken advantage of the regulatable tau transgene in APP/PS1 × rTg4510 mice. These mice develop both neurofibrillary tangles as well as amyloid-ß plaques throughout the cortex and hippocampus. By suppressing human tau expression for 6 months in the APP/PS1 × rTg4510 mice using doxycycline, AT8 tau pathology, bioactivity, and astrogliosis were reduced, though importantly to a lesser extent than lowering tau in the rTg4510 alone mice. Based on non-denaturing gels and proteinase K digestions, the remaining tau aggregates in the presence of amyloid-ß exhibit a longer-lived aggregate conformation. Nonetheless, lowering the expression of the human tau transgene was sufficient to equally ameliorate thioflavin-S positive tangles and prevent neuronal loss equally well in both the APP/PS1 × rTg4510 mice and the rTg4510 cohort. Together, these results suggest that, although amyloid-ß stabilizes tau aggregates, lowering total tau levels is still an effective strategy for the treatment of tau pathology and neuronal loss even in the presence of amyloid-ß deposition.

Risk for Low Pathogenicity Avian Influenza Virus on Poultry Farms, the Netherlands, 2007-2013.

Using annual serologic surveillance data from all poultry farms in the Netherlands during 2007-2013, we quantified the risk for the introduction of low pathogenicity avian influenza virus (LPAIV) in different types of poultry production farms and putative spatial-environmental risk factors: distance from poultry farms to clay soil, waterways, and wild waterfowl areas. Outdoor-layer, turkey (meat and breeder), and duck (meat and breeder) farms had a significantly higher risk for LPAIV introduction than did indoor-layer farms. Except for outdoor-layer, all poultry types (i.e., broilers, chicken breeders, ducks, and turkeys) are kept indoors. For all production types, LPAIV risk decreased significantly with increasing distance to medium-sized waterways and with increasing distance to areas with defined wild waterfowl, but only for outdoor-layer and turkey farms. Future research should focus not only on production types but also on distance to waterways and wild bird areas. In addition, settlement of new poultry farms in high-risk areas should be discouraged.

Predicting the Ability of Preclinical Diagnosis To Improve Control of Farm-to-Farm Foot-and-Mouth Disease Transmission in Cattle.

Foot-and-mouth disease (FMD) can cause large disruptive epidemics in livestock. Current eradication measures rely on the rapid clinical detection and removal of infected herds. Here, we evaluated the potential for preclinical diagnosis during reactive surveillance to reduce the risk of between-farm transmission. We used data from transmission experiments in cattle where both samples from individual animals, such as blood, probang samples, and saliva and nasal swabs, and herd-level samples, such as air samples, were taken daily during the course of infection. The sensitivity of each of these sample types for the detection of infected cattle during different phases of the early infection period was quantified. The results were incorporated into a mathematical model for FMD, in a cattle herd, to evaluate the impact of the early detection and culling of an infected herd on the infectious output. The latter was expressed as the between-herd reproduction ratio, Rh , where an effective surveillance approach would lead to a reduction in the Rh value to <1. Applying weekly surveillance, clinical inspection alone was found to be ineffective at blocking transmission. This was in contrast to the impact of weekly random sampling (i.e., using saliva swabs) of at least 10 animals per farm or daily air sampling (housed cattle), both of which were shown to reduce the Rh to <1. In conclusion, preclinical detection during outbreaks has the potential to allow earlier culling of infected herds and thereby reduce transmission and aid the control of epidemics.

Utilising the resources of the International Knockout Mouse Consortium: the Australian experience.

Mouse models play a key role in the understanding gene function, human development and disease. In 2007, the Australian Government provided funding to establish the Monash University embryonic stem cell-to-mouse (ES2M) facility. This was part of the broader Australian Phenomics Network, a national infrastructure initiative aimed at maximising access to global resources for understanding gene function in the mouse. The remit of the ES2M facility is to provide subsidised access for Australian biomedical researchers to the ES cell resources available from the International Knockout Mouse Consortium (IKMC). The stated aim of the IKMC is to generate a genetically modified mouse ES cell line for all of the ~23,000 genes in the mouse genome. The principal function of the Monash University ES2M service is to import genetically modified ES cells into Australia and to convert them into live mice with the potential to study human disease. Through advantages of economy of scale and established relationships with ES cell repositories worldwide, we have created over 110 germline mouse strains sourced from all of the major ES providers worldwide. We comment on our experience in generating these mouse lines; providing a snapshot of a "clients" perspective of using the IKMC resource and one which we hope will serve as a guide to other institutions or organisations contemplating establishing a similar centralised service.

T- and B-cell subsets in periodontitis.

A large amount of information is available, in the medical literature, on the molecular and immunological mechanisms in which T- and B-cells are involved in the pathogenesis of inflammatory diseases. This review attempts to describe the most important features of the T-cell subsets and their cytokine networks in periodontitis, including the interaction of pathogens with different cell subsets and their gene-expression profiles. Additionally, the known interactions of T- and B-cell subsets in periodontitis are described. The purpose of this article was to provide an overview of the cell interactions and cytokine networks specifically involved in the pathogenesis of periodontitis, and models and paradigms from recent research in this area are presented. However, the review of the literature also revealed that relatively little is known about the genetic or structural factors that confer cross-reactivity of natural and/or autoreactive antibodies in the immunopathogenesis of periodontitis. Pathogens, in turn, are continuously evolving and creating mechanisms to evade immunological reactions controlled and modulated by T- and B-cells.

An appraisal on the occurrence of foot-and-mouth disease virus serotypes in cattle and buffaloes, Pakistan.

Foot-and-mouth disease (FMD) is a livestock disease that has serious economic repercussions. Here, we report the laboratory results for samples from suspected outbreaks that were sent for confirmation of FMD in Pakistan. From January 2010 to December 2011, 132 suspected outbreaks were investigated, and samples from 58 out of the 76 outbreaks sent to the National Veterinary Laboratory (NVL) were positive. The highest proportion of positives were of serotype O (65.52 %), followed by serotype A (24.14 %) and serotype Asia-1 (10.35 %), whereas amongst the samples sent to the World Reference Laboratory, Pirbright, UK (WRL), samples from 48 out of 56 outbreaks were confirmed to be FMD positive, with the following serotypes identified: O (56.25 %), Asia-1 (37.50 %) and A (6.25 %). The outbreaks affected cattle, buffalo and mixed (cattle and buffalo) herds at rates of 91, 70 and 76 %, respectively. The trend of positive outbreaks was higher in the months of winter and late spring (November to April). Although the serotype O isolates and some of the serotype A isolates from the field samples resembled the vaccine strains (r-value ≥ 0.3), this was not the case for the Asia-1 isolates. These results help to improve our understanding of the occurrence and distribution of FMD in cattle and buffaloes in Pakistan and to provide baseline information for the FMD progressive control program in the country.

Long-term analysis of osseointegrated implants in non-smoker patients with a previous history of periodontitis.

AIM: To evaluate long-term clinical and radiographic parameters of osseointegrated implants in non-smoker patients with a previous history of chronic periodontitis. MATERIALS AND METHODS: Fifty-four screw-type implants with a moderately roughened surface and internal hexagonal implant-abutment connection were placed according to a two-phase protocol and 40 reference teeth were analysed at baseline, and after 5 and 10 years. Pocket probing depth (PPD), clinical attachment level (CAL) and bleeding on probing were analysed 6x/tooth in all teeth, implants and reference teeth. Radiographic peri-implant bone level was measured on the mesial and distal surfaces. The prevalence of peri-implantitis and the survival rate of the implants were assessed at the patient and implant levels. Data were analysed using descriptive statistics, Mann-Whitney U-test, and Wald Z-test, at α = 5%. RESULTS: In implants, the CAL at 5 years was 0.3 mm higher, and at 10 years 1.2 mm higher in comparison to baseline. The corresponding data for the reference teeth were 0 mm and 0.5 mm respectively. Multilevel testing showed statistical difference for PPD between implants and teeth over time. After 10 years, the mean mesial bone loss was 0.63 ± 0.26 mm, and the mean distal bone loss was 0.56 ± 0.25. The survival rates were 100% and 92.3% for the implants in the mandible and the implants in the maxilla respectively. CONCLUSIONS: Screw-type implants with internal hexagon placed in patients with a previous history of periodontitis attending a regular maintenance programme demonstrated stable clinical and radiographic results after 5 and 10 years.

T helper cells from aggressive periodontitis patients produce higher levels of interleukin-1 beta and interleukin-6 in interaction with Porphyromonas gingivalis.

OBJECTIVE: In this study, we analyzed the production of Interleukin-1 beta (IL-1ß) and IL-6 by activated CD4+ cells obtained from aggressive periodontitis (AgP) patients in comparison with healthy subjects (HC). MATERIALS AND METHODS: CD4+ cells were automatically separated from lymphocytes obtained from peripheral blood of patients with AgP and healthy controls. Cells were activated for 4, 8, and 24 h with three different stimuli: anti-CD3/anti-CD28, phytohemagglutinin (PHA), and Porphyromonas gingivalis (P. gingivalis) outer membrane protein (OMP). Protein levels were measured in supernatants of activated CD4+ cells by a bead-based immunoassay (CBA). In addition, serum antibodies against P. gingivalis were determined. Data were analyzed using U test (p < 0.05). RESULTS: T helper cells of AgP patients activated with P. gingivalis OMP produced higher levels of IL-1ß and IL-6 in comparison with healthy controls (p < 0.05). Neither the activation with anti-CD3/anti-CD28 nor the activation with PHA showed significantly different production of IL-1ß and IL-6 by the cells 25 % of patients and 17 % of controls presented with high serum reactivity to P. gingivalis. CONCLUSION: In view of these results, it is possible to conclude that P. gingivalis contributes to the pathogenesis of AgP by inducing high levels of pro-inflammatory cytokines such as IL-1ß and IL-6 by peripheral CD4+ T helper cells. CLINICAL RELEVANCE: In accordance with the clinical parameters and the immunological data, we suggest that full-mouth disinfection with adjunctive systemic antibiotics might be the anti-infectious non-surgical periodontal treatment of choice in this type of patients. Microbiological analyses at the beginning and at the end of the periodontal treatment are recommended. However, it is necessary to verify these data in longitudinal clinical studies.

In Ovo Models to Predict Virulence of Highly Pathogenic Avian Influenza H5-Viruses for Chickens and Ducks.

Highly pathogenic avian influenza (HPAI) H5-viruses are circulating in wild birds and are repeatedly introduced to poultry causing outbreaks in the Netherlands since 2014. The largest epizootic ever recorded in Europe was caused by HPAI H5N1 clade 2.3.4.4b viruses in the period 2021-2022. The recent H5-clade 2.3.4.4 viruses were found to differ in their virulence for chickens and ducks. Viruses causing only mild disease may remain undetected, increasing the risk of virus spread to other farms, wild birds and mammals. We developed in ovo models to determine the virulence of HPAI viruses for chickens and ducks, which are fast and have low costs. The virulence of five contemporary H5-viruses was compared studying replication rate, average time to death and virus spread in the embryo. Remarkable differences in virulence were observed between H5-viruses and between poultry species. The H5N1-2021 virus was found to have a fast replication rate in both the chicken and duck in ovo models, but a slower systemic virus dissemination compared to three other H5-clade 2.3.4.4b viruses. The results show the potential of in ovo models to quickly determine the virulence of novel HPAI viruses, and study potential virulence factors which can help to better guide the surveillance in poultry.

Discovery of common molecular signatures and drug repurposing for COVID-19/Asthma comorbidity: ACE2 and multi-partite networks.

Angiotensin-converting enzyme 2 (ACE2) is identified as the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing global coronavirus disease-2019 (COVID-19) pandemic. This study aimed to elucidate potential therapeutic avenues by scrutinizing approved drugs through the identification of the genetic signature associated with SARS-CoV-2 infection in individuals with asthma. This exploration was conducted through an integrated analysis, encompassing interaction networks between the ACE2 receptor and common host (co-host) factors implicated in COVID-19/asthma comorbidity. The comprehensive analysis involved the identification of common differentially expressed genes (cDEGs) and hub-cDEGs, functional annotations, interaction networks, gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and module construction. Interaction networks were used to identify overlapping disease modules and potential drug targets. Computational biology and molecular docking analyzes were utilized to discern functional drug modules. Subsequently, the impact of the identified drugs on the expression of hub-cDEGs was experimentally validated using a mouse model. A total of 153 cDEGs or co-host factors associated with ACE2 were identified in the COVID-19 and asthma comorbidity. Among these, seven significant cDEGs and proteins - namely, HRAS, IFNG, JUN, CDH1, TLR4, ICAM1, and SCD-were recognized as pivotal host factors linked to ACE2. Regulatory network analysis of hub-cDEGs revealed eight top-ranked transcription factors (TFs) proteins and nine microRNAs as key regulatory factors operating at the transcriptional and post-transcriptional levels, respectively. Molecular docking simulations led to the proposal of 10 top-ranked repurposable drug molecules (Rapamycin, Ivermectin, Everolimus, Quercetin, Estradiol, Entrectinib, Nilotinib, Conivaptan, Radotinib, and Venetoclax) as potential treatment options for COVID-19 in individuals with comorbid asthma. Validation analysis demonstrated that Rapamycin effectively inhibited ICAM1 expression in the HDM-stimulated mice group (p < 0.01). This study unveils the common pathogenesis and genetic signature underlying asthma and SARS-CoV-2 infection, delineated by the interaction networks of ACE2-related host factors. These findings provide valuable insights for the design and discovery of drugs aimed at more effective therapeutics within the context of lung disease comorbidities.

Avian influenza overview December 2023-March 2024.

Between 2 December 2023 and 15 March 2024, highly pathogenic avian influenza (HPAI) A(H5) outbreaks were reported in domestic (227) and wild (414) birds across 26 countries in Europe. Compared to previous years, although still widespread, the overall number of HPAI virus detections in birds was significantly lower, among other reasons, possibly due to some level of flock immunity in previously affected wild bird species, resulting in reduced contamination of the environment, and a different composition of circulating A(H5N1) genotypes. Most HPAI outbreaks reported in poultry were primary outbreaks following the introduction of the virus by wild birds. Outside Europe, the majority of outbreaks in poultry were still clustered in North America, while the spread of A(H5) to more naïve wild bird populations on mainland Antarctica is of particular concern. For mammals, A(H5N5) was reported for the first time in Europe, while goat kids in the United States of America represented the first natural A(H5N1) infection in ruminants. Since the last report and as of 12 March 2024, five human avian influenza A(H5N1) infections, including one death, three of which were clade 2.3.2.1c viruses, have been reported by Cambodia. China has reported two human infections, including one fatal case, with avian influenza A(H5N6), four human infections with avian influenza A(H9N2) and one fatal case with co-infection of seasonal influenza A(H3N2) and avian influenza A(H10N5). The latter case was the first documented human infection with avian influenza A(H10N5). Human infections with avian influenza remain rare and no sustained human-to-human infection has been observed. The risk of infection with currently circulating avian H5 influenza viruses of clade 2.3.4.4b in Europe remains low for the general population in the EU/EEA. The risk of infection remains low to moderate for those occupationally or otherwise exposed to infected animals.

Comparing the long-term persistence of different Wolbachia strains after the release of bacteria-carrying mosquitoes.

This paper proposes a bidimensional modeling framework for Wolbachia invasion, assuming imperfect maternal transmission, incomplete cytoplasmic incompatibility, and direct infection loss due to thermal stress. Our model adapts to various Wolbachia strains and retains all properties of higher-dimensional models. The conditions for the durable coexistence of Wolbachia-carrying and wild mosquitoes are expressed using the model's parameters in a compact closed form. When the Wolbachia bacterium is locally established, the size of the remanent wild population can be assessed by a direct formula derived from the model. The model was tested for four Wolbachia strains undergoing laboratory and field trials to control mosquito-borne diseases: wMel, wMelPop, wAlbB, and wAu. As all these bacterial strains affect the individual fitness of mosquito hosts differently and exhibit different levels of resistance to temperature variations, the model helped to conclude that: (1) the wMel strain spreads faster in wild mosquito populations; (2) the wMelPop exhibits lower resilience but also guarantees the smallest size of the remanent wild population; (3) the wAlbB strain performs better at higher ambient temperatures than others; (4) the wAu strain is not sustainable and cannot persist in the wild mosquito population despite its resistance to high temperatures.