Geology defines microbiome structure and composition in nunataks and valleys of the Sør Rondane Mountains, East Antarctica.

Understanding the relation between terrestrial microorganisms and edaphic factors in the Antarctic can provide insights into their potential response to environmental changes. Here we examined the composition of bacterial and micro-eukaryotic communities using amplicon sequencing of rRNA genes in 105 soil samples from the Sør Rondane Mountains (East Antarctica), differing in bedrock or substrate type and associated physicochemical conditions. Although the two most widespread taxa (Acidobacteriota and Chlorophyta) were relatively abundant in each sample, multivariate analysis and co-occurrence networks revealed pronounced differences in community structure depending on substrate type. In moraine substrates, Actinomycetota and Cercozoa were the most abundant bacterial and eukaryotic phyla, whereas on gneiss, granite and marble substrates, Cyanobacteriota and Metazoa were the dominant bacterial and eukaryotic taxa. However, at lower taxonomic level, a distinct differentiation was observed within the Cyanobacteriota phylum depending on substrate type, with granite being dominated by the Nostocaceae family and marble by the Chroococcidiopsaceae family. Surprisingly, metazoans were relatively abundant according to the 18S rRNA dataset, even in samples from the most arid sites, such as moraines in Austkampane and Widerøefjellet ("Dry Valley"). Overall, our study shows that different substrate types support distinct microbial communities, and that mineral soil diversity is a major determinant of terrestrial microbial diversity in inland Antarctic nunataks and valleys.

Oncologic and Fertility Outcomes After Simple Trachelectomy in Women With Early Cervical Cancer.

STUDY OBJECTIVE: This study aimed to present our case series of patients with early-stage cervical cancer undergoing simple trachelectomy (ST). Currently, radical trachelectomy is considered the most appropriate fertility-preserving procedure for the treatment of early-stage cervical cancer. However, there is increasing debate on the appropriate radicality of the surgery to preserve oncologic safety. DESIGN: Descriptive retrospective analysis of patient records and evaluation of questionnaires. SETTING: 2 gynecologic oncologic centers, surgeries performed by one surgical team. PATIENTS: 36 women with early-stage cervical cancer undergoing ST. INTERVENTIONS: Laparoscopic assisted simple vaginal trachelectomy. MEASUREMENTS: Demographic, histologic, fertility, and follow-up data of all patients who underwent ST between April 2007 and July 2021 were prospectively recorded and retrospectively analyzed. MAIN RESULTS: A total of 36 women (mean age: 28 years) underwent ST of whom 81% were nulliparous. Indications for ST were multifocal International Federation of Gynecology and Obstetrics stage IA1 (n = 30), stage IA1 L1 (n = 1), stage IA2 (n = 2), and stage IB1 (n = 3). Mandatory staging procedure was laparoscopic pelvic lymphadenectomy, including bilateral sentinel biopsy in 92% of the cases and systematic in 8%. Residual tumor was histologically confirmed in 8 specimens (22%); 18 women (50%) were seeking parenthood, and 13 succeeded (72%). There were 16 live births, all on term, with a median fetal weight of 3110 grams (2330-4420). One patient had a medical abortion owing to fetal congenital malformation. One pregnancy is ongoing. After a median follow-up of 91.5 months (9-174), all women are alive with no evidence of disease. CONCLUSION: ST represents a de-escalation compared with radical trachelectomy and provides excellent oncologic results with an outstanding fertility rate and obstetric outcome for patients with early cervical cancer. However, clear indications for this tailored fertility-preserving surgery have to be defined in well-designed trials.

Polar lake microbiomes have distinct evolutionary histories.

Toward the poles, life on land is increasingly dominated by microorganisms, yet the evolutionary origin of polar microbiomes remains poorly understood. Here, we use metabarcoding of Arctic, sub-Antarctic, and Antarctic lacustrine benthic microbial communities to test the hypothesis that high-latitude microbiomes are recruited from a globally dispersing species pool through environmental selection. We demonstrate that taxonomic overlap between the regions is limited within most phyla, even at higher-order taxonomic levels, with unique deep-branching phylogenetic clades being present in each region. We show that local and regional taxon richness and net diversification rate of regionally restricted taxa differ substantially between polar regions in both microeukaryotic and bacterial biota. This suggests that long-term evolutionary divergence resulting from low interhemispheric dispersal and diversification in isolation has been a prominent process shaping present-day polar lake microbiomes. Our findings illuminate the distinctive biogeography of polar lake ecosystems and underscore that conservation efforts should include their unique microbiota.

Highly divergent CRESS DNA and picorna-like viruses associated with bleached thalli of the green seaweed Ulva.

Marine macroalgae (seaweeds) are important primary producers and foundation species in coastal ecosystems around the world. Seaweeds currently contribute to an estimated 51% of the global mariculture production, with a long-term growth rate of 6% per year, and an estimated market value of more than US$11.3 billion. Viral infections could have a substantial impact on the ecology and aquaculture of seaweeds, but surprisingly little is known about virus diversity in macroalgal hosts. Using metagenomic sequencing, we characterized viral communities associated with healthy and bleached specimens of the commercially important green seaweed Ulva. We identified 20 putative new and divergent viruses, of which the majority belonged to the Circular Rep-Encoding Single-Stranded (CRESS) DNA viruses [single-stranded (ss)DNA genomes], Durnavirales [double-stranded (ds)RNA], and Picornavirales (ssRNA). Other newly identified RNA viruses were related to the Ghabrivirales, the Mitoviridae, and the Tombusviridae. Bleached Ulva samples contained particularly high viral read numbers. While reads matching assembled CRESS DNA viruses and picorna-like viruses were nearly absent from the healthy Ulva samples (confirmed by qPCR), they were very abundant in the bleached specimens. Therefore, bleaching in Ulva could be caused by one or a combination of the identified viruses but may also be the result of another causative agent or abiotic stress, with the viruses simply proliferating in already unhealthy seaweed tissue. This study highlights how little we know about the diversity and ecology of seaweed viruses, especially in relation to the health and diseases of the algal host, and emphasizes the need to better characterize the algal virosphere. IMPORTANCE Green seaweeds of the genus Ulva are considered a model system to study microbial interactions with the algal host. Remarkably little is known, however, about viral communities associated with green seaweeds, especially in relation to the health of the host. In this study, we characterized the viral communities associated with healthy and bleached Ulva. Our findings revealed the presence of 20 putative novel viruses associated with Ulva, encompassing both DNA and RNA viruses. The majority of these viruses were found to be especially abundant in bleached Ulva specimens. This is the first step toward understanding the role of viruses in the ecology and aquaculture of this green seaweed.

Fertility sparing therapy in women with lymph node negative cervical cancer >2cm - oncologic and fertility outcomes of neoadjuvant chemotherapy followed by radical vaginal trachelectomy.

OBJECTIVE: Simple or radical trachelectomy are accepted fertility sparing therapies for patients diagnosed with cervical cancer ≤2 cm. In patients with larger tumors a fertility sparing concept is considered experimental. The aim of our study is to present oncological and fertility outcomes of laparoscopic pelvic lymphadenectomy followed by neoadjuvant chemotherapy and subsequent radical vaginal trachelectomy. These procedures were performed in two centers in patients diagnosed with cervical cancer of diameter >2 cm. METHOD: We retrospectively analyzed the demographic, histological, fertility and follow-up data of all patients with cervical cancer assessed as stage IB2, IB3 or IIA1 under the International Federation of Gynecology and Obstetrics (FIGO) 2018 system. These patients had undergone pelvic lymphadenectomy, followed by neoadjuvant chemotherapy and radical vaginal trachelectomy between February 2006 and June 2020 at Charité University Berlin and Asklepios Hospital, Hamburg. RESULTS: A total of 31 patients (mean age 29.5 years, range; 26-40) underwent neoadjuvant chemotherapy followed by radical vaginal trachelectomy in case of proven tumor-free lymph nodes. Twenty-six (84%) of these patients were nulliparous. Across all 31 patients, the initial tumor stages were FIGO 2018 stage IB2 (n=27), IB3 (n=3) and IIA1 (n=1).Lymphadenectomy was completed in all but one patient (sentinel) with a median of 33 (range; 11-47) pelvic lymph nodes. The neoadjuvant chemotherapy regimen was two cycles of paclitaxel, ifosfamide and cisplatin in 17 patients; three cycles of paclitaxel, ifosfamide and cisplatin in eight patients; two cycles of paclitaxel and cisplatin in four patients; two cylces cisplatin monoagent in one patient; and two cycles of paclitaxel and cisplatin followed by two cycles of paclitaxel, ifosfamide and cisplatin in one patient. Residual tumor was histologically confirmed in 17 specimens (55%). The median residual tumor size following neoadjuvant chemotherapy was 12 mm (range; 1-60). Fertility could be preserved in 27 patients (87%); two patients underwent adjuvant chemoradiation after radical vaginal trachelectomy due to high-risk histological features; two other patients underwent radical hysterectomy with adjuvant chemoradiation therapy following neoadjuvant chemotherapy. Of 18 (67%) patients seeking motherhood, 13 became pregnant (72%). There were 12 live births in 10 women, with a median fetal weight of 2490 grams (range; 1640-3560) and five miscarriages. After a median follow-up of 94.5 months (range; 6-183) three recurrences (11.1%) were detected, one patient (3.7%) died of the disease. CONCLUSION: Neoadjuvant chemotherapy followed by radical vaginal trachelectomy may be offered to patients seeking motherhood with cervical cancer >2 cm and histopathologically tumor-free lymph nodes, the rate of healthy baby pregnancy on discharge was 10/18 women (55%). This fertility-preserving strategy is associated with higher recurrence and death compared with what was published in the literature for women undergoing radical vaginal trachelectomy for tumors up to 2 cm.

Bacterial responses to plant antimicrobials: the case of alkannin and shikonin derivatives.

Alkannin, shikonin and their derivatives (A/S) are secondary metabolites produced in the roots of certain plants of the Boraginaceae family such as Lithospermum erythrorhizon Siebold & Zucc. and Alkanna tinctoria (L.) Tausch. These naphthoquinones express anti-cancer, wound healing, and antimicrobial activities. To study the interactions between endophytic bacteria isolated from A. tinctoria and the antimicrobials A/S, endophytic bacteria known to be resistant to the compounds were screened for their effect on A/S in liquid medium. Thereafter, the strain Pseudomonas sp. R-72008, was selected and tested for its ability to modify A/S in nutrient medium and minimal medium with A/S as sole carbon source. Bacterial growth was recorded, and high performance liquid chromatography-diode array and ultra-high performance liquid chromatography-electrospray ionization-mass spectrometry analyses were performed to detect and quantify metabolites. In nutrient medium inoculated with R-72008, a decrease in the amount of A/S monomers initially present was observed and correlated with an increase of A/S oligomers. Moreover, a significant decrease of initial A/S monomers in minimal medium was correlated with bacterial growth, showing for the first time that a bacterial strain, Pseudomonas sp. R-72008, was able to use the naphthoquinones A/S as sole carbon source. This study opens new perspectives on the interactions between bacteria and plant antimicrobials.

Uncovering Genomic Features and Biosynthetic Gene Clusters in Endophytic Bacteria from Roots of the Medicinal Plant Alkanna tinctoria Tausch as a Strategy To Identify Novel Biocontrol Bacteria.

The world's population is increasing at a rate not seen in the past. Agriculture, providing food for this increasing population, is reaching its boundaries of space and natural resources. In addition, changing legislation and increased ecological awareness are forcing agriculture to reduce its environmental impact. This entails the replacement of agrochemicals with nature-based solutions. In this regard, the search for effective biocontrol agents that protect crops from pathogens is in the spotlight. In this study, we have investigated the biocontrol activity of endophytic bacteria isolated from the medicinal plant Alkanna tinctoria Tausch. To do so, an extensive collection of bacterial strains was initially genome sequenced and in silico screened for features related to plant stimulation and biocontrol. Based on this information, a selection of bacteria was tested in vitro for antifungal activity using direct antagonism in a plate assay and in planta with a detached-leaf assay. Bacterial strains were tested individually and in combinations to assess the best-performing treatments. The results revealed that many bacteria could produce metabolites that efficiently inhibit the proliferation of several fungi, especially Fusarium graminearum. Among these, Pseudomonas sp. strain R-71838 showed a strong antifungal effect, in both dual-culture and in planta assays, making it the most promising candidate for biocontrol application. Using microbes from medicinal plants, this study highlights the opportunities of using genomic information to speed up the screening of a taxonomically diverse set of bacteria with biocontrol properties. IMPORTANCE Phytopathogenic fungi are a major threat to global food production. The most common management practice to prevent plant infections involves the intensive use of fungicides. However, with the growing awareness of the ecological and human impacts of chemicals, there is a need for alternative strategies, such as the use of bacterial biocontrol agents. Limitations in the design of bacterial biocontrol included the need for labor-intensive and time-consuming experiments to test a wide diversity of strains and the lack of reproducibility of their activity against pathogens. Here, we show that genomic information is an effective tool to select bacteria of interest quickly. Also, we highlight that the strain Pseudomonas sp. R-71838 produced a reproducible antifungal effect both in vitro and in planta. These findings build a foundation for designing a biocontrol strategy based on Pseudomonas sp. R-71838.

Phylogenomics reveals insights into the functional evolution of the genus Agrobacterium and enables the description of Agrobacterium divergens sp. nov.

The genus Agrobacterium was initially described as mainly phytopathogenic strains. Nowadays, the genus includes phytopathogenic and non-phytopathogenic bacteria that are distinctive among the Rhizobiaceae family. Recently we have isolated two closely related strains, LMG 31531T and LMG 31532, from soil and plant roots, respectively. Both strains differ from previously reported species based on the genomic and phenotypic data. A. arsenijevicii KFB 330T and A. fabacearum LMG 31642T showed the highest 16S rRNA similarity (98.9 %), followed by A. nepotum LMG 26435T (98.7 %). A clear genomic feature that distinguishes LMG 31531T and LMG 31532 from other Agrobacterium species is the absence of a linear chromid. Nevertheless, typical values of the core-proteome Average Amino Acid Identity (cpAAI > 85 %) and 16S rRNA gene sequence similarity (>96 %) when compared to other members of the genus confirm the position of these two strains as part of the Agrobacterium genus. They are therefore described as Agrobacterium divergens sp. nov. Besides, our comparative genomic study and survey for clade-specific markers resulted in the discovery of conserved proteins that provide insights into the functional evolution of this genus.

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study.

BACKGROUND: The increasing use of immune checkpoint inhibitors (ICIs) in the treatment of both advanced and early stages of various malignancies has resulted in a substantial increase in the incidence of cardiovascular (CV) immune-related adverse events (irAEs). The current follow-up guidelines are based on anecdotal evidence and expert opinions, due to a lack of solid data and prospective studies. As many questions remain unanswered, cardiac monitoring, in patients receiving ICIs, is not always implemented by oncologists. Hence, an urgent need to investigate the possible short- and long-term CV effects of ICIs, as ICI approval is continuing to expand to the (neo)adjuvant setting. METHODS: We have initiated a prospective, multicenter study, i.e., the CAVACI trial, in which a minimum of 276 patients with a solid tumor, eligible for ICI treatment, will be enrolled. The study consists of routine investigations of blood parameters (troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, in particular) and a thorough CV follow-up (electrocardiograms, transthoracic echocardiograms, and coronary calcium scoring) at fixed time points for a total period of two years. The primary endpoint is the cumulative incidence of troponin elevation in the first three months of ICI treatment, compared to baseline levels. Furthermore, secondary endpoints include incidence above the upper limit of normal of both troponin and NT-proBNP levels, evolution in troponin and NT-proBNP levels, the incidence of CV abnormalities/major adverse cardiac events, evaluation of associations between patient characteristics/biochemical parameters and CV events, transthoracic echocardiography parameters, electrocardiography parameters, and progression of coronary atherosclerosis. Recruitment of patients started in January 2022. Enrolment is ongoing in AZ Maria Middelares, Antwerp University Hospital, AZ Sint-Vincentius Deinze, and AZ Sint-Elisabeth Zottegem. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05699915, registered 26 January 2023.

Salinity and host drive Ulva-associated bacterial communities across the Atlantic-Baltic Sea gradient.

The green seaweed Ulva is a model system to study seaweed-bacteria interactions, but the impact of environmental drivers on the dynamics of these interactions is little understood. In this study, we investigated the stability and variability of the seaweed-associated bacteria across the Atlantic-Baltic Sea salinity gradient. We characterized the bacterial communities of 15 Ulva sensu lato species along 2,000 km of coastline in a total of 481 samples. Our results demonstrate that the Ulva-associated bacterial composition was strongly structured by both salinity and host species (together explaining between 34% and 91% of the variation in the abundance of the different bacterial genera). The largest shift in the bacterial consortia coincided with the horohalinicum (5-8 PSU, known as the transition zone from freshwater to marine conditions). Low-salinity communities especially contained high relative abundances of Luteolibacter, Cyanobium, Pirellula, Lacihabitans and an uncultured Spirosomaceae, whereas high-salinity communities were predominantly enriched in Litorimonas, Leucothrix, Sulfurovum, Algibacter and Dokdonia. We identified a small taxonomic core community (consisting of Paracoccus, Sulfitobacter and an uncultured Rhodobacteraceae), which together contributed to 14% of the reads per sample, on average. Additional core taxa followed a gradient model, as more core taxa were shared between neighbouring salinity ranges than between ranges at opposite ends of the Atlantic-Baltic Sea gradient. Our results contradict earlier statements that Ulva-associated bacterial communities are taxonomically highly variable across individuals and largely stochastically defined. Characteristic bacterial communities associated with distinct salinity regions may therefore facilitate the host's adaptation across the environmental gradient.

[Limb fractures in pet rabbits (Oryctolagus cuniculus f. domestica) - A case series of orthopedic long-term effects in fracture patients]. / Gliedmaßenfrakturen beim Kaninchen (Oryctolagus cuniculus f. domestica).

OBJECTIVE: Limb fractures account for a large proportion of all orthopedic diseases in pet rabbits and are a common reason for presentation. The fracture etiologies and characteristics vary considerably in comparison to trauma of the extremities in cats and dogs. For this reason, conservative and surgical treatment options need to be adapted. To our knowledge, long-term effects of limb fracture therapies in pet rabbits have not been described scientifically. MATERIALS AND METHODS: This article features a case series of 13 pet rabbits with limb fractures. Their medical records were analyzed retrospectively and all patients were presented for a follow-up examination including clinical and orthopedic examination. RESULTS: Orthopedic anomalies (abducted limb postures) were identified in four patients. Arthrotic ossification was found in twelve of thirteen animals - in six cases to a high extent. Measurement of the fractured bones revealed a shortening in ten of thirteen cases. CONCLUSION AND CLINICAL RELEVANCE: Orthopedic long-term complications following fracture treatments were commonly detected in the patient population of this study. Permanent issues may result in anomalies of limb posture or postural control which are not noticed by the rabbit owners in every case. Ultimately, the patients should be examined routinely after the conclusion of fracture therapy in order to detect and adequately treat possible orthopedic complications.

More than just hitchhikers: a survey of bacterial communities associated with diatoms originating from sea turtles.

Diatoms and bacteria are known for being the first colonizers of submerged surfaces including the skin of marine reptiles. Sea turtle carapace and skin harbor diverse prokaryotic and eukaryotic microbes, including several epizoic diatoms. However, the importance of diatom-bacteria associations is hardly investigated in biofilms associated with animal hosts. This study provides an inventory of diatoms, bacteria and diatom-associated bacteria originating from loggerhead sea turtles using both metabarcoding and culturing approaches. Amplicon sequencing of the carapace and skin samples chloroplast gene rbcL and 16S rRNA gene detected, in total, 634 diatom amplicon sequence variants (ASVs) and 3661 bacterial ASVs, indicating high diversity. Cultures of putative epizoic and non-epizoic diatoms contained 458 bacterial ASVs and their bacterial assemblages reflected those of their host. Diatom strains allowed for enrichment and isolation of bacterial families rarely observed on turtles, such as Marinobacteraceae, Alteromonadaceae and Alcanivoracaceae. When accounting for phylogenetic relationships between bacterial ASVs, we observed that related diatom genera might retain similar microbial taxa in culture, regardless of the turtle's skin or carapace source. These data provide deeper insights into the sea turtle-associated microbial communities, and reveal the potential of epizoic biofilms as a source of novel microbes and possibly important diatom-bacteria associations.

Root-associated bacteria modulate the specialised metabolome of Lithospermum officinale L.

Bacteria influence plant growth and development and therefore are attractive resources for applications in agriculture. However, little is known about the impact of these microorganisms on secondary metabolite (SM) production by medicinal plants. Here we assessed, for the first time, the effects of bacteria on the modulation of SM production in the medicinal plant Lithospermum officinale (Boraginaceae family) with a focus on the naphthoquinones alkannin/shikonin and their derivatives (A/Sd). The study was conducted in an in vitro cultivation system developed for that purpose, as well as in a greenhouse. Targeted and non-targeted metabolomics were performed, and expression of the gene PGT encoding for a key enzyme in the A/S biosynthesis pathway was evaluated with qPCR. Three strains, Chitinophaga sp. R-73072, Xanthomonas sp. R-73098 and Pseudomonas sp. R-71838 induced a significant increase of A/Sd in L. officinale in both systems, demonstrating the strength of our approach for screening A/Sd-inducing bacteria. The bacterial treatments altered other plant metabolites derived from the shikimate pathway as well. Our results demonstrate that bacteria influence the biosynthesis of A/Sd and interact with different metabolic pathways. This work highlights the potential of bacteria to increase the production of SM in medicinal plants and reveals new patterns in the metabolome regulation of L. officinale.

Mesorhizobium ventifaucium sp. nov. and Mesorhizobium escarrei sp. nov., two novel root-nodulating species isolated from Anthyllis vulneraria.

Ten mesorhizobial strains isolated from root-nodules of Anthyllis vulneraria by trapping using soils from southern France were studied to resolve their taxonomy. Their 16S rDNA sequences were identical and indicated that they are affiliated to the genus Mesorhizobium within the group M. prunaredense/M. delmotii/M. temperatum/M. mediterraneum/M. wenxiniae and M. robiniae as the closest defined species. Their evolutionary relationships with validated species were further characterized by multilocus sequence analysis (MLSA) using 4 protein-coding housekeeping genes (recA, atpD, glnII and dnaK), that divides the strains in two groups, and suggest that they belong to two distinct species. These results were well-supported by MALDI-TOF mass spectrometry analyses, wet-lab DNA-DNA hybridization (≤58%), and genome-based species delineation methods (ANI < 96%, in silico DDH < 70%), confirming their affiliation to two novel species. Based on these differences, Mesorhizobium ventifaucium (STM4922T = LMG 29643T = CFBP 8438T) and Mesorhizobium escarrei (type strain STM5069T = LMG 29642T = CFBP 8439T) are proposed as names for these two novel species. The phylogeny of nodulation genes nodC and nodA allocated the type strains into symbiovar anthyllidis as well as those of M. metallidurans STM2683T, M. delmotii STM4623T and M. prunaredense STM4891T, all recovered from the same legume species.

Movement Disorders and Mortality in Severely Mentally Ill Patients: The Curacao Extrapyramidal Syndromes Study XIV.

BACKGROUND AND HYPOTHESIS: There is a substantial gap in life expectancy between patients with severe mental illness (SMI) and the general population and it is important to understand which factors contribute to this difference. Research suggests an association between tardive dyskinesia (TD) and mortality; however, results are inconclusive. In addition, studies investigating associations between parkinsonism or akathisia and mortality are rare. We hypothesized that TD would be a risk factor for mortality in patients with SMI. STUDY DESIGN: We studied a cohort of 157 patients diagnosed predominantly with schizophrenia on the former Netherlands Antilles. TD, parkinsonism, and akathisia were assessed with rating scales on eight occasions over a period of 18 years. Twenty-four years after baseline, survival status and if applicable date of death were determined. Associations between movement disorders and survival were analyzed using Cox regression. Sex, age, antipsychotics, antidepressants and benzodiazepines at each measurement occasion were tested as covariates. STUDY RESULTS: Parkinsonism was a significant risk factor with an HR of 1.02 per point on the motor subscale of the Unified Parkinson's Disease Rating Scale (range 0-56). TD and akathisia were not significantly associated with mortality. CONCLUSIONS: Parkinsonism may be an important risk factor for mortality in SMI patients. This finding calls for more follow-up and intervention studies to confirm this finding and to explore whether treatment or prevention of parkinsonism can reduce excess mortality.

The effect on relapse rate and psychiatric symptomatology: Switching a combination of first- and second-generation antipsychotic polypharmacy to antipsychotic monotherapy in long-term inpatients with schizophrenia and related disorders. A pragmatic randomized open-label trial (SwAP trial).

BACKGROUND: There is little evidence to support the use of antipsychotic polypharmacy, and there are concerns about safety and side effects. Nonetheless, it is commonly used in the treatment of long-term inpatients with schizophrenia. This study investigated the effects of switching from a combination of first- and second-generation antipsychotics (FGA and SGA) to monotherapy (FGA or SGA) on relapse rates and psychiatric symptomatology. METHODS: Institutionalized patients with chronic psychotic disorders using a combination of SGA and FGA (n = 136) participated in a randomized open-label trial. The SWITCH group discontinued either FGA or SGA, the STAY group continued combination treatment. Relapse and psychotic symptoms were measured at baseline and during follow-up at 3, 6, and 9 months. Psychiatric symptomatology was measured using the Brief Psychiatric Rating Scale (BPRS). Relapse was defined as (i) an increase in BPRS score of at least 2 points on any item, or (ii) an increase of at least 4 points in total BPRS score and an adjustment of antipsychotics. RESULTS: A logistic regression model, corrected for sex, showed that the probability of relapse was significantly lower in the SWITCH group: 0.29 (95% CI 0.13-0.62). The protective effect of switching to monotherapy was attributable to patients continuing clozapine as monotherapy. For patients who did not experience a relapse nor dropped out, BPRS total scores decreased significantly more in the SWITCH group (p = 0.0001). CONCLUSION: Switching from a combination of FGA and SGA to monotherapy in long-term inpatients does not increase the relapse rate and may even reduce it.

Flemish soils contain rhizobia partners for Northwestern Europe-adapted soybean cultivars.

In Europe, soybean (Glycine max) used for food and feed has to be imported, causing negative socioeconomic and environmental impacts. To increase the local production, breeding generated varieties that grow in colder climates, but the yield using the commercial inoculants is not satisfactory in Belgium because of variable nodulation efficiencies. To look for indigenous nodulating strains possibly adapted to the local environment, we initiated a nodulation trap by growing early-maturing cultivars under natural and greenhouse conditions in 107 garden soils in Flanders. Nodules occurred in 18 and 21 soils in the garden and greenhouse experiments respectively. By combining 16S rRNA PCR on single isolates with HiSeq 16S metabarcoding on nodules, we found a large bacterial richness and diversity from different soils. Furthermore, using Oxford Nanopore Technologies sequencing of DNA from one nodule, we retrieved the entire genome of a Bradyrhizobium species, not previously isolated, but profusely present in that nodule. These data highlight the need of combining diverse identification techniques to capture the true nodule rhizobial community. Eight selected rhizobial isolates were subdivided by whole-genome analysis in three genera containing six genetically distinct species that, except for two, aligned with known type strains and were all able to nodulate soybean in the laboratory.

Selection constrains lottery assembly in the microbiomes of closely related diatom species.

It is generally recognised that interactions between microalgae and bacteria play an important role in the functioning of marine ecosystems. In this context, increasing attention is paid to the processes that shape microalga-associated microbiomes. In recent years, conflicting evidence has been reported with respect to the relative importance of selective vs neutral processes in the assembly process. Whereas some studies report strong selection imposed by the host, others propose a more neutral, lottery-like assembly model according to which the chance of bacteria becoming part of the microbiome is proportional to their abundance in the environment and not driven by the selectional pressure created by the host. In the present study, we investigated to what degree selective vs neutral assembly processes constrain taxonomic, phylogenetic and functional variation within and between microbiomes associated with 69 isolates belonging to the Cylindrotheca closterium benthic marine diatom complex. The diatom cultures were initiated from non-axenic clonal isolates from different marine environments and geographic locations, and were then reared in a common garden (lab) environment. An important environmental imprint, likely due to in situ lottery dynamics, was apparent in the diatom microbiomes. However, microbiome assembly was also phylogenetically and functionally constrained through selective filtering related to the host microhabitat. Randomised microbiome assembly simulations revealed evidence for phylogenetic overdispersion in the observed microbiomes, reflecting an important role in the assembly process for competition between bacteria on the one hand and predominantly genetically driven differences between the hosts on the other hand. Our study thus shows that even between closely related diatom strains, host selection affects microbiome assembly, superimposing the predominantly stochastically driven recruitment process.

R othia mucilaginosa is an anti-inflammatory bacterium in the respiratory tract of patients with chronic lung disease.

BACKGROUND: Chronic airway inflammation is the main driver of pathogenesis in respiratory diseases such as severe asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF) and bronchiectasis. While the role of common pathogens in airway inflammation is widely recognised, the influence of other microbiota members is still poorly understood. METHODS: We hypothesised that the lung microbiota contains bacteria with immunomodulatory activity which modulate net levels of immune activation by key respiratory pathogens. Therefore, we assessed the immunomodulatory effect of several members of the lung microbiota frequently reported as present in CF lower respiratory tract samples. RESULTS: We show that Rothia mucilaginosa, a common resident of the oral cavity that is also often detectable in the lower airways in chronic disease, has an inhibitory effect on pathogen- or lipopolysaccharide-induced pro-inflammatory responses, in vitro (three-dimensional cell culture model) and in vivo (mouse model). Furthermore, in a cohort of adults with bronchiectasis, the abundance of Rothia species was negatively correlated with pro-inflammatory markers (interleukin (IL)-8 and IL-1ß) and matrix metalloproteinase (MMP)-1, MMP-8 and MMP-9 in sputum. Mechanistic studies revealed that R. mucilaginosa inhibits NF-κB pathway activation by reducing the phosphorylation of IκBα and consequently the expression of NF-κB target genes. CONCLUSIONS: These findings indicate that the presence of R. mucilaginosa in the lower airways potentially mitigates inflammation, which could in turn influence the severity and progression of chronic respiratory disorders.

Impacts of environmental stress on resistance and resilience of algal-associated bacterial communities.

Algal-associated bacteria are fundamental to the ecological success of marine green macroalgae such as Caulerpa. The resistance and resilience of algal-associated microbiota to environmental stress can promote algal health and genetic adaptation to changing environments. The composition of bacterial communities has been shown to be unique to algal morphological niches. Therefore, the level of response to various environmental perturbations may in fact be different for each niche-specific community. Factorial in situ experiments were set up to investigate the effect of nutrient enrichment and temperature stress on the bacterial communities associated with Caulerpa cylindracea. Bacteria were characterized using the 16S rRNA gene, and the community compositions were compared between different parts of the algal thallus (endo-, epi-, and rhizomicrobiome). Resistance and resilience were calculated to further understand the changes of microbial composition in response to perturbations. The results of this study provide evidence that nutrient enrichment has a significant influence on the taxonomic and functional structure of the epimicrobiota, with a low community resistance index observed for both. Temperature and nutrient stress had a significant effect on the rhizomicrobiota taxonomic composition, exhibiting the lowest overall resistance to change. The functional performance of the rhizomicrobiota had low resilience to the combination of stressors, indicating potential additive effects. Interestingly, the endomicrobiota had the highest overall resistance, yet the lowest overall resilience to environmental stress. This further contributes to our understanding of algal microbiome dynamics in response to environmental changes.