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Abstract The increasing prevalence of threats and violence against ambulance clinicians is a critical issue that has not been adequately studied. These incidents pose significant challenges to the provision of prehospital emergency care, affecting both the safety and well-being of the clinicians involved. This study aimed to explore the experiences of Swedish ambulance clinicians when encountering threats and violence during their work. A qualitative approach was used, involving semi-structured interviews with 11 ambulance clinicians from various regions of Sweden. The participants were selected to ensure diversity in gender, age, and educational background. The data were collected over three weeks in 2021 and analyzed using qualitative content analysis. The analysis revealed three key categories related to the challenges faced by ambulance clinicians: Police cooperation challenges, Strategies for a safe care environment, and Impact during and relief after stressful events. These categories highlight the complexities of managing threats and violence in the field. This study sheds light on the multifaceted challenges that ambulance clinicians face due to threats and violence. It underscores the urgent need for comprehensive training, effective communication, and clear role allocation in complex situations. Furthermore, it emphasizes the importance of organized support systems to help clinicians cope with the aftermath of stressful events.

This qualitative thematic study aimed to examine the placement of unaccompanied asylum-seeking minors in compulsory institutional care in Sweden, to expand knowledge regarding their care and treatment. The dataset comprised official documents and anonymized journal documents from personnel detailing the experiences of twenty-five unaccompanied asylum-seeking minors in compulsory institutional care organized by the Swedish National Board of Institutional Care in 2015. The study identified three main themes: traumatic life events and mental health, alignment between needs, goals, and treatment, and language difficulties. The findings revealed a high prevalence of severe traumatic experiences among the asylum-seeking minors, with half having endured significant psychological and physical trauma. Mental health issues were inconsistently addressed, and prior traumas were often overlooked in care planning. The majority exhibited various mental health problems, underscoring the need for tailored interventions. The study highlights challenges in aligning unaccompanied asylum-seeking minors' individual needs, treatment goals, and provided care. Language barriers emerged as a critical concern, impeding effective communication and treatment. Approximately 80% of the asylum-seeking minors experienced difficulties in understanding and expressing themselves in Swedish. The limited use of professional interpreters further exacerbated this issue. The study underscores the need for targeted interventions to better support unaccompanied asylum-seeking minors within compulsory institutional settings.

Mycotoxins, toxic secondary metabolites produced by certain fungi, pose significant threats to global food safety and public health. These compounds can contaminate a variety of crops, leading to economic losses and health risks to both humans and animals. Traditional lab analysis methods for mycotoxin detection can be time-consuming and may not always be suitable for large-scale screenings. However, in recent years, machine learning (ML) methods have gained popularity for use in the detection of mycotoxins and in the food safety industry in general due to their accurate and timely predictions. We provide a systematic review on some of the recent ML applications for detecting/predicting the presence of mycotoxin on a variety of food ingredients, highlighting their advantages, challenges, and potential for future advancements. We address the need for reproducibility and transparency in ML research through open access to data and code. An observation from our findings is the frequent lack of detailed reporting on hyperparameters in many studies and a lack of open source code, which raises concerns about the reproducibility and optimisation of the ML models used. The findings reveal that while the majority of studies predominantly utilised neural networks for mycotoxin detection, there was a notable diversity in the types of neural network architectures employed, with convolutional neural networks being the most popular.

Abstract With the ongoing evolution of the SARS-CoV-2 virus updated vaccines may be needed. We fitted a model linking immunity levels and protection to vaccine effectiveness data from England for three vaccines (Oxford/AstraZeneca AZD1222, Pfizer-BioNTech BNT162b2, Moderna mRNA-1273) and two variants (Delta, Omicron). Our model reproduces the observed sustained protection against hospitalisation and death from the Omicron variant over the first six months following dose 3 with the ancestral vaccines but projects a gradual waning to moderate protection after 1 year. Switching the fourth dose to a variant-matched vaccine against Omicron BA.1/2 is projected to prevent nearly twice as many hospitalisations and deaths over a 1-year period compared to administering the ancestral vaccine. This result is sensitive to the degree to which immunogenicity data can be used to predict vaccine effectiveness and uncertainty regarding the impact that infection-induced immunity (not captured here) may play in modifying future vaccine effectiveness.

Summary: Background: The underlying health status of populations was a major determinant of the impact of the COVID-19 pandemic, particularly obesity prevalence. Mexico was one of the most severely affected countries during the COVID-19 pandemic and its obesity prevalence is among the highest in the world. It is unknown by how much the COVID-19 burden could have been reduced if systemic actions had been implemented to reduce excess weight in Mexico before the onset of the pandemic. Methods: Using a dynamic epidemic model based on nationwide data, we compare actual deaths with those under hypothetical scenarios assuming a lower body mass index in the Mexican population, as observed historically. We also model the number of deaths that would have been averted due to earlier implementation of front-of-pack warning labels or due to increases in taxes on sugar-sweetened beverages and non-essential high-energy foods in Mexico. Findings: We estimate that 52.5% (95% prediction interval (PI) 43.2, 61.6%) of COVID-19 deaths were attributable to obesity for adults aged 20–64 and 23.8% (95% PI 18.7, 29.1%) for those aged 65 and over. Had the population BMI distribution remained as it was in 2000, 2006, or 2012, COVID-19 deaths would have been reduced by an expected 20.6% (95% PI 16.9, 24.6%), 9.9% (95% PI 7.3, 12.9%), or 6.9% (95% PI 4.5, 9.5%), respectively. If the food-labelling intervention introduced in 2020 had been introduced in 2018, an expected 6.2% (95% PI 5.2, 7.3%) of COVID-19 deaths would have been averted. If taxes on sugar-sweetened beverages and high-energy foods had been doubled, trebled, or quadrupled in 2018, COVID-19 deaths would have been reduced by an expected 4.1% (95% PI 2.5, 5.7%), 7.9% (95% PI 4.9, 11.0%), or 11.6% (95% PI 7.3, 15.8%), respectively. Interpretation: Public health interventions targeting underlying population health, including non-communicable chronic diseases, is a promising line of action for pandemic preparedness that should be included in all pandemic plans. Funding: This study received funding from Bloomberg Philanthropies, awarded to Juan A. Rivera from the National Institute of Public Health; Community Jameel, the UK Medical Research Council (MRC), Kenneth C Griffin, and the World Health Organization.

[This corrects the article DOI: 10.1371/journal.pone.0258726.].

Assessment has become increasingly integral to college and university accreditation. While formal assessment has become more of a responsibility for instructors as related to their individual classes and assignments, program assessment is also at the center of these conversations. However, few guidelines and resources are being shared with regard to the formal assessment of program learning outcomes. Here, we detail a step-by-step process for conducting a formal assessment of a communication studies program. Specifically, we share our procedures, findings, and implications related to assessment of one communication studies program.

BackgroundVaccines have reduced severe disease and death from Coronavirus Disease 2019 (COVID-19). However, with evidence of waning efficacy coupled with continued evolution of the virus, health programmes need to evaluate the requirement for regular booster doses, considering their impact and cost-effectiveness in the face of ongoing transmission and substantial infection-induced immunity.Methods and findingsWe developed a combined immunological-transmission model parameterised with data on transmissibility, severity, and vaccine effectiveness. We simulated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and vaccine rollout in characteristic global settings with different population age-structures, contact patterns, health system capacities, prior transmission, and vaccine uptake. We quantified the impact of future vaccine booster dose strategies with both ancestral and variant-adapted vaccine products, while considering the potential future emergence of new variants with modified transmission, immune escape, and severity properties. We found that regular boosting of the oldest age group (75+) is an efficient strategy, although large numbers of hospitalisations and deaths could be averted by extending vaccination to younger age groups. In countries with low vaccine coverage and high infection-derived immunity, boosting older at-risk groups was more effective than continuing primary vaccination into younger ages in our model. Our study is limited by uncertainty in key parameters, including the long-term durability of vaccine and infection-induced immunity as well as uncertainty in the future evolution of the virus.ConclusionsOur modelling suggests that regular boosting of the high-risk population remains an important tool to reduce morbidity and mortality from current and future SARS-CoV-2 variants. Our results suggest that focusing vaccination in the highest-risk cohorts will be the most efficient (and hence cost-effective) strategy to reduce morbidity and mortality.

3D printing is a process of making three-dimensional solid objects from a digital file process created by laying down successive layers of material until the object is created. Many filaments can be used in 3D printing, one of which is PETG (PolyEthylene Terephthalate Glycol). PETG is a modification of PET (PolyEthylene Terephthalate) with added glycol at a molecular level to offer different chemical properties that provide significant chemical resistance, durability, and excellent formability for manufacturing. This study aims to find the most optimal parameter of surface roughness of PETG with different parameters of nozzle temperature, infill geometry, layer height and fan speed. Taguchi L16 (44), with four levels for each parameter, was used to determine the effect of each parameter. Each experiment was repeated five times to minimize the occurrence of errors. Based on the result, the effect of each parameter is nozzle temperature at 4.9%, infill geometry at 5.9%, layer height at 82.3%, and fan speed at 4.6%. Layer height has the highest effect on surface roughness, and other parameters have a low effect, under 7%. Research shows that the optimal combination of parameters is a nozzle temperature of 220 °C, infill geometry zig-zag, layer height of 0.12 mm, and a fan speed of 80 %.

Abstract Background We evaluated the microbiota in the stomach of Gastroesophageal Reflux Disease (GERD) patients. We compared Erosive Reflux Disease (ERD) to gastritis and Non-erosive Reflux Disease (NERD) subjects by 16S rRNA approach on gastric biopsy specimens. A total of 197 subjects were included consisting of gastritis (68; 34.52%), ERD (55; 27.92%), and NERD (74; 37.56%). After quality filtering, 187 samples were included for OTU analysis using Qiime2. Results We observed a significant difference in alpha diversity (Shannon and Simpson indexes were P = 0.0016 and P = 0.017, respectively). A significant decrease in alpha diversity index was observed in NERD with Helicobacter pylori (H. pylori)-positive subjects than in gastritis (Simpson index P = 0.022; Shannon index P = 0.029), indicating a significant influence of H. pylori on the diversity in the stomach despite the diseases. In H. pylori-negative samples, alpha diversity measurement by the abundance coverage estimates (ACE) and Fisher Test revealed that ERD had significantly lower richness than gastritis and NERD groups (P = 0.00012 and P = 0.00043, respectively). Anaerobacillus sp. could only be found in ERD patients by LEFse analysis. Conclusions The presence of ERD could alter microbiome diversity. A negative correlation between H. pylori and ERD is shown in this microbiome study but not in NERD.

Objective Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one’s physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. Methods Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. Results Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. Conclusion This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.

Fusarium fungi produce a diverse array of mycotoxic metabolites during the pathogenesis of cereals. Some, such as the trichothecenes and fumonisins, are phytotoxic, acting as non-proteinaceous effectors that facilitate disease development in cereals. Over the last few decades, we have gained some depth of understanding as to how trichothecenes and fumonisins interact with plant cells and how plants deploy mycotoxin detoxification and resistance strategies to defend themselves against the producer fungi. The cereal-mycotoxin interaction is part of a co-evolutionary dance between Fusarium and cereals, as evidenced by a trichothecene-responsive, taxonomically restricted, cereal gene competing with a fungal effector protein and enhancing tolerance to the trichothecene and resistance to DON-producing F. graminearum. But the binary fungal–plant interaction is part of a bigger ecosystem wherein other microbes and insects have been shown to interact with fungal mycotoxins, directly or indirectly through host plants. We are only beginning to unravel the extent to which trichothecenes, fumonisins and other mycotoxins play a role in fungal-ecosystem interactions. We now have tools to determine how, when and where mycotoxins impact and are impacted by the microbiome and microfauna. As more mycotoxins are described, research into their individual and synergistic toxicity and their interactions with the crop ecosystem will give insights into how we can holistically breed for and cultivate healthy crops.

Background: T-type Ca2+ channels (Cav3) represent emerging therapeutic targets for a range of neurological disorders, including epilepsy and pain. To aid the development and optimisation of new therapeutics, there is a need to identify novel chemical entities which act at these ion channels. A number of synthetic cannabinoid receptor agonists (SCRAs) have been found to exhibit activity at T-type channels, suggesting that cannabinoids may provide convenient chemical scaffolds on which to design novel Cav3 inhibitors. However, activity at cannabinoid type 1 (CB1) receptors can be problematic because of central and peripheral toxicities associated with potent SCRAs. The putative SCRA MEPIRAPIM and its analogues were recently identified as Cav3 inhibitors with only minimal activity at CB1 receptors, opening the possibility that this scaffold may be exploited to develop novel, selective Cav3 inhibitors. Here we present the pharmacological characterisation of SB2193 and SB2193F, two novel Cav3 inhibitors derived from MEPIRAPIM.Methods: The potency of SB2193 and SB2193F was evaluated in vitro using a fluorometric Ca2+ flux assay and confirmed using whole-cell patch-clamp electrophysiology. In silico docking to the cryo-EM structure of Cav3.1 was also performed to elucidate structural insights into T-type channel inhibition. Next, in vivo pharmacokinetic parameters in mouse brain and plasma were determined using liquid chromatography-mass spectroscopy. Finally, anticonvulsant activity was assayed in established genetic and electrically-induced rodent seizure models.Results: Both MEPIRAPIM derivatives produced potent inhibition of Cav3 channels and were brain penetrant, with SB2193 exhibiting a brain/plasma ratio of 2.7. SB2193 was further examined in mouse seizure models where it acutely protected against 6 Hz-induced seizures. However, SB2193 did not reduce spontaneous seizures in the Scn1a+/− mouse model of Dravet syndrome, nor absence seizures in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS). Surprisingly, SB2193 appeared to increase the incidence and duration of spike-and-wave discharges in GAERS animals over a 4 h recording period.Conclusion: These results show that MEPIRAPIM analogues provide novel chemical scaffolds to advance Cav3 inhibitors against certain seizure types.

A review of the extant literature reveals the extent to which the spread of communicable diseases will be significantly impacted by climate change. Specific research into how this will likely be observed in the countries of the Gulf Cooperation Council (GCC) is, however, greatly lacking. This report summarises the unique public health challenges faced by the GCC countries in the coming century, and outlines the need for greater investment in public health research and disease surveillance to better forecast the imminent epidemiological landscape. Significant data gaps currently exist regarding vector occurrence, spatial climate measures, and communicable disease case counts in the GCC — presenting an immediate research priority for the region. We outline policy work necessary to strengthen public health interventions, and to facilitate evidence-driven mitigation strategies. Such research will require a transdisciplinary approach, utilising existing cross-border public health initiatives, to ensure that such investigations are well-targeted and effectively communicated.

Abstract Background Chitosan has shown potential for the control of Fusarium head blight (FHB) disease caused by Fusarium graminearum. The objective of this study was to compare the effect of chitosan hydrochloride applied pre- or post-fungal inoculation on FHB and to better understand its’ mode of action via an untargeted metabolomics study. Results Chitosan inhibited fungal growth in vitro and, when sprayed on the susceptible wheat cultivar Remus 24 hours pre-inoculation with F. graminearum, it significantly reduced the number of infected spikelets at 7, 14 and 21 days post-inoculation. Chitosan pre-treatment also increased the average grain weight per head, the number of grains per head and the 1000-grain weight compared to the controls sprayed with water. No significant impact of chitosan on grain yield was observed when the plants were sprayed 24 hours post-inoculation with F. graminearum, even if it did result in a reduced number of infected spikelets at every time point. An untargeted metabolomic study using UHPLC-QTOF-MS on wheat spikes revealed that spraying the spikes with both chitosan and F. graminearum activated known FHB resistance pathways (e.g. jasmonic acid). Additionally, more metabolites were up- or down-regulated when both chitosan and F. graminearum spores were sprayed on the spikes (117), as compared with chitosan (51) or F. graminearum on their own (32). This included a terpene, a terpenoid and a liminoid previously associated with FHB resistance. Conclusions In this study we showed that chitosan hydrochloride inhibited the spore germination and hyphal development of F. graminearum in vitro, triggered wheat resistance against infection by F. graminearum when used as a pre-inoculant, and highlighted metabolites and pathways commonly and differentially affected by chitosan, the pathogen and both agents. This study provides insights into how chitosan might provide protection or stimulate wheat resistance to infection by F. graminearum. It also unveiled new putatively identified metabolites that had not been listed in previous FHB or chitosan-related metabolomic studies.

IntroductionInadequate antimicrobial treatment has led to multidrug-resistant (MDR) bacteria, including Helicobacter pylori (H. pylori), which one of the notable pathogens in the stomach. Antibiotic-induced changes in the microbiota can negatively affect the host. This study aimed to determine the influence of H. pylori resistance on the diversity and abundance of the stomach microbiome.MethodsBacterial DNA was extracted from biopsy samples of patients presenting dyspepsia symptoms with H. pylori positive from cultures and histology. DNA was amplified from the V3-V4 regions of the 16S rRNA gene. In-vitro E-test was used to detect antibiotic resistance. Microbiome community analysis was conducted through α-diversity, β-diversity, and relative abundance.ResultsSixty-nine H. pylori positive samples were eligible after quality filtering. Following resistance status to five antibiotics, samples were classified into 24 sensitive, 24 single resistance, 16 double resistance, 5 triple resistance. Samples were mostly resistant to metronidazole (73.33%; 33/45). Comparation of four groups displayed significantly elevated α-diversity parameters under the multidrug resistance condition (all P ConclusionOur results suggest that the resistant samples showed a higher trend of diversity and evenness than the sensitive samples. The abundance of H. pylori in the triple-resistant samples decreased with increasing cohabitation of pathogenic bacteria, which may support antimicrobial resistance. However, antibiotic susceptibility determined by the E-test may not completely represent the resistance status.

The COVID-19 pandemic and the mitigation policies implemented in response to it have resulted in economic losses worldwide. Attempts to understand the relationship between economics and epidemiology has led to a new generation of integrated mathematical models. The data needs for these models transcend those of the individual fields, especially where human interaction patterns are closely linked with economic activity. In this article, we reflect upon modelling efforts to date, discussing the data needs that they have identified, both for understanding the consequences of the pandemic and policy responses to it through analysis of historic data and for the further development of this new and exciting interdisciplinary field.

Helicobacter pylori infects more than half the human population. However, the prevalence in Indonesia is low, as is the prevalence of gastric cancer. Hence, it could be instructive to compare these prevalence rates and their determining factors with those of countries that have high gastric cancer incidence. Ethnicity and genetic characteristics of H. pylori are important determinants of the H. pylori infection rate in Indonesia. The infection rate is higher in Bataknese, Papuans and Buginese than in Javanese, the predominant ethnic group. Ethnicity is also an important determinant of the genetic characteristics of H. pylori. Analysis of CagA in the EPIYA segment showed that the predominant genotypes in Papuans, Bataknese and Buginese are ABB-, ABDand ABC-type CagA, respectively. Meanwhile, in the countries with high gastric cancer incidence, almost all strains had East Asian type CagA. An antibiotic susceptibility evaluation showed that the standard triple therapy can still be used with caution in several cities. There is a very high rate of resistance to second-line regimens such as levofloxacin and metronidazole. Recent studies have shown that furazolidone, rifabutin and sitafloxacin are potential alternative treatments for antibiotic-resistant H. pylori infection in Indonesia. Rather than focusing on early detection and eradication as in countries with high gastric cancer prevalence, countries with low gastric cancer prevalence should focus on screening the several groups that have a high risk of gastric cancer.

The wheat NAC transcription factor TaNACL-D1 enhances resistance to the economically devastating Fusarium head blight (FHB) disease. The objective of this study was to decipher the alterations in gene expression, pathways and biological processes that led to enhanced resistance as a result of the constitutive expression of TaNACL-D1 in wheat. Transcriptomic analysis was used to determine the genes and processes enhanced in wheat due to TaNACL-D1 overexpression, both in the presence and absence of the causal agent of FHB, Fusarium graminearum (0- and 1-day post-treatment). The overexpression of TaNACL-D1 resulted in more pronounced transcriptional reprogramming as a response to fungal infection, leading to the enhanced expression of genes involved in detoxification, immune responses, secondary metabolism, hormone biosynthesis, and signalling. The regulation and response to JA and ABA were differentially regulated between the OE and the WT. Furthermore, the results suggest that the OE may more efficiently: (i) regulate the oxidative burst; (ii) modulate cell death; and (iii) induce both the phenylpropanoid pathway and lignin synthesis. Thus, this study provides insights into the mode of action and downstream target pathways for this novel NAC transcription factor, further validating its potential as a gene to enhance FHB resistance in wheat.

Abstract Background Even though the incidence of H. pylori infection among Malays in the Malay Peninsula is low, we observed a high H. pylori prevalence in Sumatra, which is the main residence of Indonesian Malays. H. pylori prevalence among Indonesian Malay descendants was investigated. Results Using a combination of five tests, 232 recruited participants were tested for H- pylori and participants were considered positive if at least one test positive. The results showed that the overall H. pylori prevalence was 17.2%. Participants were then categorized into Malay (Aceh, Malay, and Minang), Java (Javanese and Sundanese), Nias, and Bataknese groups. The prevalence of H. pylori was very low among the Malay group (2.8%) and no H. pylori was observed among the Aceh. Similarly, no H. pylori was observed among the Java group. However, the prevalence of H. pylori was high among the Bataknese (52.2%) and moderate among the Nias (6.1%). Multilocus sequence typing showed that H. pylori in Indonesian Malays classified as hpEastAsia with a subpopulation of hspMaori, suggesting that the isolated H. pylori were not a specific Malays H. pylori. Conclusions Even though the ethnic groups live together as a community, we observed an extremely low H. pylori infection rate among Indonesian Malay descendants with no specific Indonesian Malay H. pylori. The results suggest that H. pylori was not originally among these groups and H. pylori was imported from other ethnic groups.

Muhammad Miftahussurur,1,2 Adinta Windia,1 Ari Fahrial Syam,3 Iswan Abbas Nusi,1 Ricky Indra Alfaray,2,4 Kartika Afrida Fauzia,2,4 Hartono Kahar,5 Herry Purbayu,1 Titong Sugihartono,1 Poernomo Boedi Setiawan,1 Ummi Maimunah,1 Ulfa Kholili,1 Husin Thamrin,1 Amie Vidyani,1 Dalla Doohan,2 Langgeng Agung Waskito,2 Yudith Annisa Ayu Rezkitha,2,6 Gontar Alamsyah Siregar,7 Yoshio Yamaoka1,4 1Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, 60286, Indonesia; 2Institute of Tropical Disease, Universitas Airlangga, Surabaya, East Java, 60115, Indonesia; 3Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, 10430, Indonesia; 4Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5593, Japan; 5Department of Clinical Pathology, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, 60286, Indonesia; 6Faculty of Medicine, University of Muhammadiyah Surabaya, Surabaya, East Java, 60113, Indonesia; 7Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatra Utara, Medan, 20155, IndonesiaCorrespondence: Muhammad MiftahussururGastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine, Dr. Soetomo Teaching Hospital, Universitas Airlangga, Jalan Mayjend Prof. Dr. Moestopo No. 6– 8, Surabaya, 60286, IndonesiaTel/Fax +6231-502-3865Email muhammad-m@fk.unair.ac.idPurpose: Histopathology method is often used as a gold standard diagnostic for Helicobacter pylori infection in Indonesia. However, it requires an endoscopic procedure which is limited in Indonesia. A non-invasive method, such as 14C Urea Breath Test (UBT), is more favorable; however, this particular method has not been validated yet.Patients and Methods: A total of 55 dyspeptic patients underwent gastroscopy and 14C-UBT test. We used Heliprobe® UBT for UBT test. As for the histology, May-Giemsa staining of two gastric biopsies (from the antrum and corpus) were evaluated following the Updated Sydney System.Results: The Receiver Operating Characteristics analysis showed that the optimum cut-off value was 57 with excellence Area under Curve = 0.955 (95% CI = 0.861– 1.000). By applying the optimum cut-off value, Heliprobe® UBT showed 92.31% for sensitivity, 97.62% for specificity, 92.31% for positive predictive value, 97.62% for negative predictive value, 38.77 for positive likelihood ratio, 0.0788 for negative likelihood ratio, and 96.36% for the accuracy.Conclusion: The 14C-UBT is an accurate test for H. pylori diagnosis with excellent sensitivity, specificity, and accuracy. The different optimum cut-off points suggested that a validation is absolutely necessary for new test prior application to the new population.Keywords: Helicobacter pylori, UBT, diagnostic, infectious disease

Fusarium head blight (FHB) is a devastating disease encountered by spring-grown barley. Traditionally, synthetic chemicals have been used to control this disease on small grain cereals. A move toward biological control agents as part of sustainable agriculture is pertinent due to the evolutionary mechanisms employed by fungal diseases to circumvent current protection strategies. This study evaluated the effect of six lactic acid bacteria isolates on the development of FHB under in vitro and glasshouse conditions. The relative expression of Fusarium marker genes and transcription factors under Fusarium infection was examined. Dual-culture assays observed inhibition zones of up to 10 and 17% of total plate area for L. amylovorus FST 2.11 and L. brevis R2Δ, respectively. Detached leaf assays validated the antifungal activity and showed the potential of all test isolates to significantly inhibit sporulation of Fusarium culmorum and Fusarium graminearum strains. Spray inoculation of lactic acid bacteria to barley spikelets prior to Fusarium spore application significantly reduced disease severity for five candidates (P < 0.05) under glasshouse conditions. Mycotoxin analysis revealed the ability of L. amylovorus DSM20552 to significantly reduce deoxynivalenol content in spikelets (P < 0.05). A preliminary gene expression study showed the positive influence of lactic acid bacteria on the expression of important defense-related marker genes and transcription factors upon FHB. These results indicate the potential of lactic acid bacteria to be included as part of an integrated pest management strategy for the management of FHB disease. This strategy will reduce FHB severity and deoxynivalenol (DON) contamination of spring barley, leading to high acceptance in the grain market.

Abstract There is increasing evidence that some functionally related, co-expressed genes cluster within eukaryotic genomes. We present a novel pipeline that delineates such eukaryotic gene clusters. Using this tool for bread wheat, we uncovered 44 clusters of genes that are responsive to the fungal pathogen Fusarium graminearum. As expected, these Fusarium-responsive gene clusters (FRGCs) included metabolic gene clusters, many of which are associated with disease resistance, but hitherto not described for wheat. However, the majority of the FRGCs are non-metabolic, many of which contain clusters of paralogues, including those implicated in plant disease responses, such as glutathione transferases, MAP kinases, and germin-like proteins. 20 of the FRGCs encode nonhomologous, non-metabolic genes (including defence-related genes). One of these clusters includes the characterised Fusarium resistance orphan gene, TaFROG. Eight of the FRGCs map within 6 FHB resistance loci. One small QTL on chromosome 7D (4.7 Mb) encodes eight Fusarium-responsive genes, five of which are within a FRGC. This study provides a new tool to identify genomic regions enriched in genes responsive to specific traits of interest and applied herein it highlighted gene families, genetic loci and biological pathways of importance in the response of wheat to disease.

Abstract Background Little is known about the initial, symptomless (latent) phase of the devastating wheat disease Septoria tritici blotch. However, speculations as to its impact on fungal success and disease severity in the field have suggested that a long latent phase is beneficial to the host and can reduce inoculum build up in the field over a growing season. The winter wheat cultivar Stigg is derived from a synthetic hexaploid wheat and contains introgressions from wild tetraploid wheat Triticum turgidum subsp. dicoccoides, which contribute to cv. Stigg’s exceptional STB resistance, hallmarked by a long latent phase. We compared the early transcriptomic response to Zymoseptoria tritici of cv. Stigg to a susceptible wheat cultivar, to elucidate the mechanisms of and differences in pathogen recognition and disease response in these two hosts. Results The STB-susceptible cultivar Longbow responds to Z. tritici infection with a stress response, including activation of hormone-responsive transcription factors, post translational modifications, and response to oxidative stress. The activation of key genes associated with these pathways in cv. Longbow was independently observed in a second susceptible wheat cultivar based on an independent gene expression study. By comparison, cv. Stigg is apathetic in response to STB, and appears to fail to activate a range of defence pathways that cv. Longbow employs. Stigg also displays some evidence of sub-genome bias in its response to Z. tritici infection, whereas the susceptible cv. Longbow shows even distribution of Z. tritici responsive genes across the three wheat sub-genomes. Conclusions We identify a suite of disease response genes that are involved in early pathogen response in susceptible wheat cultivars that may ultimately lead to susceptibility. In comparison, we hypothesise that rather than an active defence response to stave off disease progression, cv. Stigg’s defence strategy is molecular lethargy, or a lower-amplitude of pathogen recognition that may stem from cv. Stigg’s wild wheat-derived ancestry. Overall, we present insights into cv. Stigg’s exceptional resistance to STB, and present key biological processes for further characterisation in this pathosystem.

Abstract Objective For evaluating the antibiotic resistance of Helicobacter pylori, the agar dilution method is the gold standard; however, using this method in daily practice is laborious. E-test has been proposed to be an uncomplicated method. This study was aimed at validating the E-test and detecting the presence of any bias between the agar dilution method and E-test. Results The agar dilution method and E-test were performed using five antibiotics for 72 strains of H. pylori obtained from clinical patients in Indonesia. The E-test’s results showed a higher prevalence of resistance to all the antibiotics tested but the difference was not significant. Results showed high essential agreement (> 90.0%) for all the antibiotics, but only 84.7% for metronidazole. The agreement for MIC value was acceptable for levofloxacin, clarithromycin, and metronidazole. For amoxicillin, it showed only fair agreement (0.25) by the Kappa analysis and significant difference by Passing-Bablok regression. Even though some discrepancies were found, the E-test has an acceptable agreement for levofloxacin, metronidazole, tetracycline, and clarithromycin but further confirmation may be necessary for amoxicillin.

Wheat occupies a special role in global food security since, in addition to providing 20% of our carbohydrates and protein, almost 25% of the global production is traded internationally. The importance of wheat for food security was recognised by the Chief Agricultural Scientists of the G20 group of countries when they endorsed the establishment of the Wheat Initiative in 2011. The Wheat Initiative was tasked with supporting the wheat research community by facilitating collaboration, information and resource sharing and helping to build the capacity to address challenges facing production in an increasingly variable environment. Many countries invest in wheat research. Innovations in wheat breeding and agronomy have delivered enormous gains over the past few decades, with the average global yield increasing from just over 1 tonne per hectare in the early 1960s to around 3.5 tonnes in the past decade. These gains are threatened by climate change, the rapidly rising financial and environmental costs of fertilizer, and pesticides, combined with declines in water availability for irrigation in many regions. The international wheat research community has worked to identify major opportunities to help ensure that global wheat production can meet demand. The outcomes of these discussions are presented in this paper.

The serine protease inhibitor (serpin) gene family is the largest family of protease inhibitors. Serine protease inhibitors have an active, but under-characterized, role in grain development and defense against pathogen attack in cereal crops. By exploiting publicly available genomic, transcriptomic and proteomic data for wheat (Triticum aestivum), we have identified and annotated the entire ’serpinome’ of wheat and constructed a high-quality and robust phylogenetic tree of the gene family, identifying paralogous and homeologous clades from the hexaploid wheat genome, including the Serpin-Z group that have been well characterized in barley. Using publicly available RNAseq data (http://www.wheat-expression.com/), expression profiles of the wheat serpins were explored across a variety of tissues from the developing grain, spikelet and spike. We show that the SERPIN-Z clade, among others, are highly expressed during grain development, and that there is homeologous and paralogous functional redundancy in this gene family. Further to their role in grain development, serpins play an important but under-explored role in response to fungal pathogens. Using 13 RNAseq datasets of wheat tissues infected by fungal pathogens, we identified 37 serpins with a significant disease response. The majority of the disease-responsive serpins were upregulated by Fusarium graminearum, a destructive fungal pathogen that attacks the spike and developing grain of wheat. As serpins are ubiquitous in wheat grain, the genes encoding serpins may be linked to grain development, with their disease response a result of pleiotropy.

Abstract Background Nepal and Bangladesh have a high prevalence of Helicobacter pylori with high resistance rates to clarithromycin, metronidazole, and levofloxacin. Here, we evaluated the susceptibility and genetic mutations of 5 alternative antibiotics against isolates from both countries to obtain an effective treatment regimen for H. pylori eradication. Methods We used the agar dilution method to determine the minimal inhibitory concentration of 5 alternative antibiotics against 42 strains from Nepal and 56 from Bangladesh and performed whole genome mutation analysis. Results No resistance to furazolidone or rifabutin and a high susceptibility of sitafloxacin (95.2% in Nepal and 98.2% in Bangladesh) were observed. In contrast, resistance to rifaximin (52.4% in Nepal and 64.3% in Bangladesh) was high. Moreover, resistance to garenoxacin was higher in Bangladesh (51.6%) than in Nepal (28.6%, P = 0.041), most likely due to its correlation with levofloxacin resistance (P = 0.03). Garenoxacin and rifaximin were significantly correlated in Bangladesh (P = 0.014) and occurred together with all sitafloxacin-resistant strains. Mutations of gyrA could play a significant role in garenoxacin resistance, and double mutations of A87 and D91 were associated with sitafloxacin resistance. Analysis of the rpoB gene demonstrated well-known mutations, such as V657I, and several novel mutations, including I2619V, V2592 L, T2537A, and F2538 L. Conclusions Rifabutin can be cautiously implemented as therapy for H. pylori infection due to its interaction with the tuberculosis endemic in Bangladesh. The high susceptibility of furazolidone and sitafloxacin suggests their possible future application in Nepal and Bangladesh.

Fusarium head blight (FHB) is an economically important disease of wheat that results in yield loss and grain contaminated with fungal mycotoxins that are harmful to human and animal health. Herein we characterised two wheat genes involved in the FHB response in wheat: a wheat mitochondrial phosphate transporter (TaMPT) and a methyltransferase (TaSAM). Wheat has three sub-genomes (A, B, and D) and gene expression studies demonstrated that TaMPT and TaSAM homoeologs were differentially expressed in response to FHB infection and the mycotoxigenic Fusarium virulence factor deoxynivalenol (DON) in FHB resistant wheat cv. CM82036 and susceptible cv. Remus. Virus-induced gene silencing (VIGS) of either TaMPT or TaSAM enhanced the susceptibility of cv. CM82036 to FHB disease, reducing disease spread (Type II disease resistance). VIGS of TaMPT and TaSAM significantly reduced grain number and grain weight. This indicates TaSAM and TaMPT genes also contribute to grain development in wheat and adds to the increasing body of evidence linking FHB resistance genes to grain development. Hence, Fusarium responsive genes TaSAM and TaMPT warrant further study to determine their potential to enhance both disease resistance and grain development in wheat.