Salt in stools is associated with obesity, gut halophilic microbiota and Akkermansia muciniphila depletion in humans.

BACKGROUND/OBJECTIVES: High salt intake has been linked to several diseases including obesity and an increased risk of death; however, fecal salinity and the ability of salt to alter the gut microbiota, which was recently identified as an instrumental factor for health and disease, remains poorly explored. METHODS/SUBJECTS: We analyzed the fecal samples of 1326 human individuals for salinity by refractometry, 572 for gut microbiota by culturomics, and 164 by 16S rRNA-targeted metagenomics. Geographical origin, age, gender, and obesity were tested as predictors of fecal salinity and halophilic diversity. All halophilic isolates were characterized by taxonogenomics and their genome sequenced. RESULTS: Fecal salinity was associated with obesity independently of geographical origin, gender, and age. The first 2 human-associated halophilic archaeal members were isolated along with 64 distinct halophilic species, including 21 new species and 41 known in the environment but not in humans. No halophiles grow in less than 1.5% salinity. Above this threshold, the richness of the halophilic microbiota was correlated with fecal salinity (r = 0.58, p < 0.0001). 16S metagenomics linked high fecal salinity to decreased diversity (linear regression, p < .035) and a depletion in anti-obesity Akkermansia muciniphila and Bifidobacterium, specifically B. longum and B. adolescentis. Genomics analysis suggested that halophilic microbes are not only transient passengers but may be residents of the human gut. CONCLUSIONS: High salt levels are associated with alteration of the gut microbial ecosystem and halophilic microbiota, as discovered during this study. Further studies should clarify if the gut microbiota alterations associated with high salt levels and the human halophilic microbiota could be causally related to human disease, such as obesity.

Amustaline (S-303) treatment inactivates high levels of Chikungunya virus in red-blood-cell components.

BACKGROUND AND OBJECTIVES: Chikungunya virus (CHIKV) infections have been reported in all continents, and the potential risk for CHIKV transfusion-transmitted infections (TTIs) was demonstrated by the detection of CHIKV RNA-positive donations in several countries. TTIs can be reduced by pathogen inactivation (PI) of blood products. In this study, we evaluated the efficacy of amustaline and glutathione (S-303/GSH) to inactivate CHIKV in red-blood-cell concentrates (RBCs). MATERIAL AND METHODS: Red-blood-cells were spiked with high level of CHIKV. Infectious titres and RNA loads were measured before and after PI treatment. Residual CHIKV infectivity was also assessed after five successive cell culture passages. RESULTS: The mean CHIKV titres in RBCs before inactivation was 5·81 ± 0·18 log10 50% tissue culture infectious dose (TCID50 )/mL, and the mean viral RNA load was 10·49 ± 0·15 log10 genome equivalent (GEq)/mL. No CHIKV TCID was detected after S-303 treatment nor was replicative CHIKV particles and viral RNA present after five cell culture passages of samples obtained immediately after S-303 treatment. CONCLUSION: Chikungunya virus was previously shown to be inactivated by the PI technology using amotosalen and ultraviolet A light for the treatment of plasma and platelets. This new study demonstrates that S-303/GSH can inactivate high titres of CHIKV in RBCs.

A novel combination of peripheral nerve blocks for arthroscopic shoulder surgery.

BACKGROUND: Interscalene brachial plexus block is currently the gold standard for intra- and post-operative pain management for patients undergoing arthroscopic shoulder surgery. However, it is associated with block related complications, of which effect on the phrenic nerve have been of most interest. Side effects caused by general anesthesia, when this is required, are also a concern. We hypothesized that the combination of superficial cervical plexus block, suprascapular nerve block, and infraclavicular brachial plexus block would provide a good alternative to interscalene block and general anesthesia. METHODS: Twenty adult patients scheduled for arthroscopic shoulder surgery received a combination of superficial cervical plexus block (5 ml ropivacaine 0.5%), suprascapular nerve block (4 ml ropivacaine 0.5%), and lateral sagittal infraclavicular block (31 ml ropivacaine 0.75%). The primary aim was to find the proportion of patients who could be operated under light propofol sedation, without the need for opioids or artificial airway. Secondary aims were patients' satisfaction and surgeons' judgment of the operating conditions. RESULTS: Nineteen of twenty patients (95% CI: 85-100) underwent arthroscopic shoulder surgery with light propofol sedation, but without opioids or artificial airway. The excluded patient was not comfortable in the beach chair position and therefore received general anesthesia. All patients were satisfied with the treatment on follow-up interviews. The surgeons rated the operating conditions as good for all patients. CONCLUSION: The novel combination of a superficial cervical plexus block, a suprascapular nerve block, and an infraclavicular nerve block provides an alternative anesthetic modality for arthroscopic shoulder surgery.

Sensitivity of real-time PCR performed on dried sera spotted on filter paper for diagnosis of leptospirosis.

In remote countries, leptospirosis confirmation is difficult because it requires the shipment of frozen samples to reference laboratories. The sensitivity of leptospirosis real-time PCR performed on filter paper-dried serum samples stored at ambient temperature was evaluated at 2 × 10(2) equivalent leptospires/ml (eqLeptospires/ml). This easy alternative procedure can be used to enhance the surveillance of leptospirosis.

Zika virus infection complicated by Guillain-Barre syndrome--case report, French Polynesia, December 2013.

Zika fever, considered as an emerging disease of arboviral origin, because of its expanding geographic area, is known as a benign infection usually presenting as an influenza-like illness with cutaneous rash. So far, Zika virus infection has never led to hospitalisation. We describe the first case of Guillain-Barré syndrome (GBS) occurring immediately after a Zika virus infection, during the current Zika and type 1 and 3 dengue fever co-epidemics in French Polynesia.

Potential for Zika virus transmission through blood transfusion demonstrated during an outbreak in French Polynesia, November 2013 to February 2014.

Since October 2013, French Polynesia has experienced the largest documented outbreak of Zika virus (ZIKAV) infection. To prevent transmission of ZIKAV by blood transfusion, specific nucleic acid testing of blood donors was implemented. From November 2013 to February 2014: 42 (3%) of 1,505 blood donors, although asymptomatic at the time of blood donation, were found positive for ZIKAV by PCR. Our results serve to alert blood safety authorities about the risk of post-transfusion Zika fever.

Absence of Zika virus among pregnant women in Vietnam in 2008.

BACKGROUND: Despite being first identified in 1947, Zika virus-related outbreaks were first described starting from 2007 culminating with the 2015 Latin American outbreak. Hypotheses indicate that the virus has been circulating in Asia for decades, but reports are scarce. METHODS: We performed serological analysis and screened placental samples isolated in 2008 for the presence of Zika virus from pregnant women in Ho Chi Minh City (Vietnam). RESULTS: None of the placental samples was positive for Zika virus. Four serum samples out of 176 (2.3%) specifically inhibited Zika virus, with variable degrees of cross-reactivity with other flaviviruses. While one of the four samples inhibited only Zika virus, cross-reactivity with other flaviviruses not included in the study could not be ruled out. CONCLUSION: Our results support the conclusion that the virus was not present among pregnant women in the Vietnamese largest city during the initial phases of the epidemic wave.

Leprosy in French Polynesia.

Leprosy is a neglected endemic infectious disease in the Pacific region. In French Polynesia (FP), leprosy is no longer a public health problem at the national level, defined by the World Health Organization as a prevalence rate below 1 case per 10,000 population. However, even if its incidence has dramatically declined in FP in the last decades, leprosy is still endemic at a low level. Here we present a case of leprosy in a 34-year-old man from FP diagnosed in 2018. Clinical and microbiologic examinations, including fluorescence in-situ hybridization, led to the diagnosis of a multibacillary leprosy, and multidrug therapy was initiated. There is a need to maintain leprosy surveillance and trained medical staff for the detection and treatment of new cases.

Leptospirosis in French Polynesia: 11 years of surveillance data, 2007-2017.

Leptospirosis is a worldwide zoonosis with higher incidence in tropical areas and is a neglected disease in the Pacific region. French Polynesia (FP) is a French overseas territory located in the South Pacific. Data on the epidemiology in FP are scarce. In this study, we describe our understanding of leptospirosis epidemiology in FP and discuss the prospects concerning this disease and its surveillance to better address preventive actions. We report 11 years of surveillance data between 1 January 2007 and 31 December 2017. Over the study period, 1356 confirmed and probable leptospirosis cases were reported. The mean annual incidence rate was 46.0 (95% confidence interval, 43.6-48.5) cases per 100 000 inhabitants. We registered 864 (63.7%) hospitalizations; of these, at least 270 (19.9%) were in the intensive care unit, and 24 patients (1.8%) died. Even if the incidence of leptospirosis is lower in FP compared to most of other Pacific countries and territories, our data confirm that the disease is highly endemic in FP. Despite all the preventive measures taken, leptospirosis remains a major public health concern in FP, thus highlighting the need to maintain intensive leptospirosis surveillance, medical staff training and provision of information to the general population.

Comparison of the gut microbiota of obese individuals from different geographic origins.

Few studies have examined the interaction of human geography, microbial community structure and obesity. We tested obese adult volunteers from France, Saudi Arabia, French Polynesia and from a traditional population in the village of Trois-Sauts in French Guiana by sequencing the V3-V4 region. We also sequenced homemade fermented cachiri beers that were obtained from the traditional Amazonian population and are highly consumed by this population. We found that French and Saudis had significantly less richness and biodiversity in their gut microbiota than Amazonians and Polynesians (p <0.05). Principle coordinate analysis of the overall composition of the genera communities revealed that the microbiomes of Amazonians clustered independently from the other obese individuals. Moreover, we found that Amazonians presented significantly stricter anaerobic genera than the Saudis, French and Polynesians (p < 0.001). Polynesians presented significantly lower relative abundance of Lactobacillus sp. than French (p 0.01) and Saudis (p 0.05). Treponema berlinense and Treponema succinifaciens were only present in the gut microbiome of Amazonians. The cachiri beers presented significantly more bacterial species in common with the gut microbiome of Amazonians (p < 0.005). Obese individuals with different origins present modifications in their gut microbiota, and we provide evidence that the cachiri beers influenced the gut microbiome of Amazonians.

Treponema species enrich the gut microbiota of traditional rural populations but are absent from urban individuals.

There is a significant gap in our knowledge of the microbe-host relationship between urban and traditional rural populations. We conducted a large-scale study to examine the gut microbiota of different traditional rural and urban lifestyles in human populations. Using high-throughput 16S ribosomal RNA gene amplicon sequencing, we tested urban French, Saudi, Senegalese, Nigerian and Polynesian individuals as well as individuals living in traditional rural societies, including Amazonians from French Guiana, Congolese Pygmies, Saudi Bedouins and Algerian Tuaregs. The gut microbiota from individuals living in traditional rural settings clustered differently and presented significantly higher diversity than those of urban populations (p 0.01). The bacterial taxa identified by class analysis as contributing most significantly to each cluster were Phascolarctobacterium for traditional rural individuals and Bifidobacterium for urban individuals. Spirochaetae were only present in the gut microbiota of individuals from traditional rural societies, and the gut microbiota of all traditional rural populations was enriched with Treponema succinifaciens. Cross-transmission of Treponema from termites or swine to humans or the increased use of antibiotics in nontraditional populations may explain why Treponema is present only in the gut microbiota of traditional rural populations.

"Mycobacterium massilipolynesiensis" sp. nov., a rapidly-growing mycobacterium of medical interest related to Mycobacterium phlei.

In French Polynesia, respiratory tract clinical isolate M26, displayed unusual phenotype and contradictory phylogenetic affiliations, suggesting a hitherto unidentified rapidly-growing Mycobacterium species. The phenotype of strain M26 was further characterized and its genome sequenced. Strain M26 genome consists in a 5,732,017-bp circular chromosome with a G + C% of 67.54%, comprising 5,500 protein-coding genes and 52 RNA genes (including two copies of the 16 S rRNA gene). One region coding for a putative prophage was also predicted. An intriguing characteristic of strain M26's genome is the large number of genes encoding polyketide synthases and nonribosomal peptide synthases. Phylogenomic analysis showed that strain M26's genome is closest to the Mycobacterium phlei genome with a 76.6% average nucleotide identity. Comparative genomics of 33 Mycobacterium genomes yielded 361 genes unique to M26 strain which functional annotation revealed 84.21% of unknown function and 3.88% encoding lipid transport and metabolism; while 48.87% of genes absent in M26 strain have unknown function, 9.5% are implicated in transcription and 19% are implicated in transport and metabolism. Strain M26's unique phenotypic and genomic characteristics indicate it is representative of a new species named "Mycobacterium massilipolynesiensis". Looking for mycobacteria in remote areas allows for the discovery of new Mycobacterium species.

Detection of Zika virus RNA in semen of asymptomatic blood donors.

OBJECTIVES: Zika virus (ZIKV) transmission through semen donation has never been reported but the risk is supported by the detection of ZIKV in semen and the demonstration of ZIKV sexual transmission. The potential impact of ZIKV on assisted reproductive procedures should be evaluated. METHODS: We tested longitudinally collected semen samples provided by asymptomatic blood donors who tested positive for ZIKV RNA in plasma during ZIKV outbreaks in Puerto Rico and Florida in 2016. RESULTS: Five of the 14 (35.7%) asymptomatic blood donors provided semen samples that tested positive for ZIKV RNA, with ZIKV RNA loads ranging from 8.03 × 103 to 2.55 × 106 copies/mL. Plasma collected at the same time as the semen tested negative for ZIKV RNA for most ZIKV RNA-positive semen collections; all corresponding plasma samples tested positive or equivocal for anti-ZIKV IgG antibodies and all except one tested positive for ZIKV IgM antibodies. The rate of detection of ZIKV RNA in semen in asymptomatic donors is not significantly different from the rate previously reported for symptomatic patients. CONCLUSIONS: Our results that show a high percentage of detection of ZIKV RNA in the semen of asymptomatic men confirm that ZIKV is a new threat for reproductive medicine and should have important implications for assisted reproductive technology. We recommend that semen donations from men at risk for ZIKV infection should be tested for ZIKV RNA, regardless of symptoms of ZIKV infection.

Genome sequence and description of Actinomyces polynesiensis str. MS2 sp. nov. isolated from the human gut.

Actinomyces polynesiensis strain MS2 gen. nov., sp. nov. is a newly proposed genus within the family Actinomycetaceae, isolated from the stools of a healthy individual in Raiatea Island (French Polynesia, South Pacific). Actinomyces massiliensis is an anaerobic, Gram-positive organism. Here we describe the features of this organism, together with the complete genome sequence and annotation-2 943 271 bp with a 70.80% G+C content, assembled into 15 scaffolds and containing 2080 genes.

Symptomatic Venous Thromboembolism and Major Bleeding After Renal Transplantation: Should We Use Pharmacologic Thromboprophylaxis?

BACKGROUND: Venous thromboembolism (VTE) is a major health issue that may result in complications such as post-thrombotic syndrome, pulmonary hypertension, and death. Appropriate thromboprophylaxis in individuals undergoing kidney transplantation remains unclear. The aim of this study was to determine the prevalence of symptomatic VTE and major bleeding within 90 days after renal transplantation (RT). METHODS: This was a retrospective study on consecutive patients undergoing RT at Hospital Privado Córdoba, Argentina, from January 1, 2006, to December 31, 2013. Exclusion criteria were age <18 years and combined organ transplantation. Pharmacologic or mechanical thromboprophylaxis was not used routinely. Symptomatic VTE and major bleeding were documented. RESULTS: A total of 511 RTs were performed; 62 patients received combined organ transplantation, and 8 patients (1.5%) were lost to follow-up. Overall, follow-up was completed on 441 patients, 4 (0.9%) of whom developed deep venous thrombosis and 14 (3%) of whom died. The most frequent causes of death were septic shock and severe hemorrhage. Duration of surgery >4 hours (P = .006) and a history of VTE (P < .001) were associated with VTE. Twenty-three patients (5.2%) had major bleeding, 2 (0.4%) died from bleeding complications, and 17 (3.85%) required a reoperation to control bleeding. CONCLUSIONS: This study shows a low prevalence of symptomatic VTE in patients undergoing RT despite not having used thromboprophylaxis routinely. Major bleeding was significant, and despite the high risk of VTE assigned by the Caprini score, which suggests pharmacologic prophylaxis, our data raise questions about the appropriate prophylaxis for these patients.

The effect of a venous filter on the embolic load during medullary canal pressurization: a canine study.

BACKGROUND: Acute intramedullary stabilization of femoral shaft fractures in multiply injured patients is controversial. Intravasation of medullary fat during canal pressurization has been suspected to trigger adult respiratory distress syndrome. The goal of the present study was to evaluate the effect, on the lungs, of a filter placed into the ipsilateral common iliac vein during medullary canal pressurization in a canine model. METHODS: With use of an established model of fat embolization, twelve mongrel dogs were randomized into two groups. In six dogs, a special filter was inserted percutaneously into the left common iliac vein while the dogs were under general anesthesia. In all dogs, the left femur and tibia were then pressurized by injection of bone cement and insertion of intramedullary rods. Hemodynamic measurements and echocardiographic images were recorded throughout the experiment. After one hour, the animals were killed and the lungs were harvested for histomorphometric analysis. RESULTS: Without the filter, the mean pulmonary artery pressure increased by 11.8 +/- 2.1 mm Hg (p < 0.001). With the filter, the mean pulmonary artery pressure increased by only 2.2 +/- 0.8 mm Hg (p < 0.02). Without the filter, there was a significant increase in the index of pulmonary vascular resistance as compared with the baseline value (p < 0.05). With the filter, there was no such increase. Histomorphometric analysis demonstrated that the presence of the filter reduced the absolute area of embolization and the volume percentages of lung and pulmonary vasculature embolized. CONCLUSIONS: In this canine experiment, temporary placement of a venous filter prior to medullary canal pressurization reduced the embolic load and minimized its hemodynamic effects.

Inhibition of uridine phosphorylase: synthesis and structure-activity relationships of aryl-substituted 5-benzyluracils and 1-[(2-hydroxyethoxy)methyl]-5-benzyluracils.

A series of 1-[(2-hydroxyethoxy)methyl]-5-benzyluracils were synthesized and tested for inhibition of murine liver uridine phosphorylase (UrdPase). Inhibitors of UrdPase are reported to enhance the chemotherapeutic utility of 5-fluoro-2'-deoxyuridine and 5-fluorouracil and to ameliorate zidovudine-induced anemia in animal models. We prepared a series of 5-aryl-substituted analogues of 5-benzylacyclouridine (BAU), a good inhibitor of UrdPase (IC50 of 0.46 microM), to develop a compound with enhanced potency and improved pharmacokinetics. The first phase of structure-activity relationship studies on a series of 32 aryl-substituted 5-benzyluracils found several 5-(3-alkoxybenzyl) analogues of 5-benzyluracil with enhanced potency. The acyclovir side chain, the (2-hydroxyethoxy)methyl group, was substituted on the more potent aryl-substituted 5-benzyluracils. The two most potent compounds, 10y (3-propoxy) and 10dd (3-sec-butoxy), were inhibitors of UrdPase with IC50s of 0.047 and 0.027 microM, respectively. Six compounds were tested in vivo for effects on steady-state concentrations of circulating uridine in rats. Plasma uridine levels were elevated 3-9-fold by compound levels that ranged from 8 to 50 microM.

Inhibition of uridine phosphorylase. Synthesis and structure-activity relationships of aryl-substituted 1-((2-hydroxyethoxy)methyl)-5-(3-phenoxybenzyl)uracil.

Structure-activity relationship studies on a series of 1-((2-hydroxyethoxy)methyl)-5-(3-(substituted-phenoxy)benzyl)uracils as inhibitors of murine liver uridine phosphorylase have led to compounds with IC50s as low as 1.4 nM. The two most potent compounds, 10j (3-cyanophenoxy) and 11f (3-chlorophenoxy) were tested in vivo for effects on steady-state concentrations of circulating uridine in mice and rats. Both compounds were substantially more efficacious than BAU (5-benzylacyclouridine) both in vitro and in vivo.