The selective advantage of facultative anaerobes relies on their unique ability to cope with changing oxygen levels during infection.

Bacteria, including those that are pathogenic, have been generally classified according to their ability to survive and grow in the presence or absence of oxygen: aerobic and anaerobic bacteria, respectively. Strict aerobes require oxygen to grow (e.g., Neisseria), and strict anaerobes grow exclusively without, and do not survive oxygen exposure (e.g., Clostridia); aerotolerant bacteria (e.g., Lactobacilli) are insensitive to oxygen exposure. Facultative anaerobes (e.g., E. coli) have the unique ability to grow in the presence or in the absence of oxygen and are thus well-adapted to these changing conditions, which may constitute an underestimated selective advantage for infection. In the WHO antibiotic-resistant 'priority pathogens' list, facultative anaerobes are overrepresented (8 among 12 listed pathogens), consistent with clinical studies performed in populations particularly susceptible to infectious diseases. Bacteria aerobic respiratory chain plays a central role in oxygen consumption, leading to the formation of hypoxic infectious sites (infectious hypoxia). Facultative anaerobes have developed a wide diversity of aerotolerance and anaerotolerance strategies in vivo. However, at a single cell level, the modulation of the intracellular oxygen level in host infected cells remains elusive and will be discussed in this review. In conclusion, the ability of facultative bacteria to evolve in the presence or the absence of oxygen is essential for their virulence strategy and constitute a selective advantage. TAKE AWAY: Most life-threatening pathogenic bacteria are facultative anaerobes. Only facultative anaerobes are aerotolerant, anaerotolerant and capable of consuming O2 . Facultative anaerobes induce and are well adapted to cellular hypoxia.

Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and antipsychotics: a large, prospective cohort study.

BACKGROUND: Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease-inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed. OBJECTIVE: To determine associations of autoantibody reactivities with comorbidities and concomitant medication. METHODS: In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti-BP180 NC16A and anti-BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed. RESULTS: An association between higher serum anti-BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase-4 (DPP4) inhibitors, inhibitors of platelet aggregation and L-thyroxine. The use of DPP4 inhibitors was associated with less anti-BP180 and anti-BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti-BP180 and anti-BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L-thyroxine. CONCLUSION: Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD.

Reducing neutrophil exposure to oxygen allows their basal state maintenance.

Neutrophils are the most abundant circulating white blood cells and are the central players of the innate immune response. During their lifecycle, neutrophils mainly evolve under low oxygen conditions (0.1-4% O2 ), to which they are well adapted. Neutrophils are atypical cells since they are highly glycolytic and susceptible to oxygen exposure, which induces their activation and death through mechanisms that remain currently elusive. Nevertheless, nearly all studies conducted on neutrophils are carried out under atmospheric oxygen (21%), corresponding to hyperoxia. Here, we investigated the impact of hyperoxia during neutrophil purification and culture on neutrophil viability, activation and cytosolic protein content. We demonstrate that neutrophil hyper-activation (CD62L shedding) is induced during culture under hyperoxic conditions (24 h), compared with neutrophils cultured under anoxic conditions. Spontaneous neutrophil extracellular trap (NET) formation is observed when neutrophils face hyperoxia during purification or culture. In addition, we show that maintaining neutrophils in autologous plasma is the preferred strategy to maintain their basal state. Our results show that manipulating neutrophils under hyperoxic conditions leads to the loss of 57 cytosolic proteins during purification, while it does not lead to an immediate impact on neutrophil activation (CD11bhigh , CD54high , CD62Lneg ) or viability (DAPI+ ). We identified two clusters of proteins belonging to cholesterol metabolism and to the complement and coagulation cascade pathways, which are highly susceptible to neutrophil oxygen exposure during neutrophil purification. In conclusion, protecting neutrophil from oxygen during their purification and culture is recommended to avoid activation and to prevent the alteration of cytosolic protein composition.

High Arctic Holocene temperature record from the Agassiz ice cap and Greenland ice sheet evolution.

We present a revised and extended high Arctic air temperature reconstruction from a single proxy that spans the past ∼12,000 y (up to 2009 CE). Our reconstruction from the Agassiz ice cap (Ellesmere Island, Canada) indicates an earlier and warmer Holocene thermal maximum with early Holocene temperatures that are 4-5 °C warmer compared with a previous reconstruction, and regularly exceed contemporary values for a period of ∼3,000 y. Our results show that air temperatures in this region are now at their warmest in the past 6,800-7,800 y, and that the recent rate of temperature change is unprecedented over the entire Holocene. The warmer early Holocene inferred from the Agassiz ice core leads to an estimated ∼1 km of ice thinning in northwest Greenland during the early Holocene using the Camp Century ice core. Ice modeling results show that this large thinning is consistent with our air temperature reconstruction. The modeling results also demonstrate the broader significance of the enhanced warming, with a retreat of the northern ice margin behind its present position in the mid Holocene and a ∼25% increase in total Greenland ice sheet mass loss (∼1.4 m sea-level equivalent) during the last deglaciation, both of which have implications for interpreting geodetic measurements of land uplift and gravity changes in northern Greenland.

The ace-1 Locus Is Amplified in All Resistant Anopheles gambiae Mosquitoes: Fitness Consequences of Homogeneous and Heterogeneous Duplications.

Gene copy-number variations are widespread in natural populations, but investigating their phenotypic consequences requires contemporary duplications under selection. Such duplications have been found at the ace-1 locus (encoding the organophosphate and carbamate insecticides' target) in the mosquito Anopheles gambiae (the major malaria vector); recent studies have revealed their intriguing complexity, consistent with the involvement of various numbers and types (susceptible or resistant to insecticide) of copies. We used an integrative approach, from genome to phenotype level, to investigate the influence of duplication architecture and gene-dosage on mosquito fitness. We found that both heterogeneous (i.e., one susceptible and one resistant ace-1 copy) and homogeneous (i.e., identical resistant copies) duplications segregated in field populations. The number of copies in homogeneous duplications was variable and positively correlated with acetylcholinesterase activity and resistance level. Determining the genomic structure of the duplicated region revealed that, in both types of duplication, ace-1 and 11 other genes formed tandem 203kb amplicons. We developed a diagnostic test for duplications, which showed that ace-1 was amplified in all 173 resistant mosquitoes analyzed (field-collected in several African countries), in heterogeneous or homogeneous duplications. Each type was associated with different fitness trade-offs: heterogeneous duplications conferred an intermediate phenotype (lower resistance and fitness costs), whereas homogeneous duplications tended to increase both resistance and fitness cost, in a complex manner. The type of duplication selected seemed thus to depend on the intensity and distribution of selection pressures. This versatility of trade-offs available through gene duplication highlights the importance of large mutation events in adaptation to environmental variation. This impressive adaptability could have a major impact on vector control in Africa.

The current distribution and characterization of the L1014F resistance allele of the kdr gene in three malaria vectors (Anopheles gambiae, Anopheles coluzzii, Anopheles arabiensis) in Benin (West Africa).

BACKGROUND: The fight against malaria faces various biological obstacles, including the resistance of parasites to anti-malarial drugs and the resistance of mosquito vectors to insecticides. The resistance of Anopheles gambiae sensu lato (s.l.) to pyrethroids, the only class of insecticides used to impregnate mosquito nets, is known in Benin; the expansion of this resistance is influenced by the existence of gene flow between species, otherwise by the presence or absence of the kdr mutation in them. The objective of this study is to determine the spatial distribution of An. gambiae and the level of expression of the pyrethroid resistance kdr gene in seven agro-ecological zones of Benin. METHODS: The study was conducted in 18 localities belonging to seven agro-ecological zones where environmental parameters varied. The sites represent the main areas of eco-epidemiological malaria in Benin. Anopheles gambiae larvae were collected in natural breeding sites using ladles and dipping method and reared under standard conditions. These larvae were reared under standard conditions of temperature and humidity (26 to 30 °C and 60 to 90%) at the insectarium of the Centre de Recherche Entomologique de Cotonou (CREC). Adult female mosquitoes having emerged are morphologically and molecularly identified. Homozygous resistant (1014F/1014F), homozygous sensitive (1014L/1014L) and heterozygous (1014F/1014L) genotypes of the L1014F kdr gene mutation are determined by PCR. RESULTS: A total of 677 An. gambiae was subjected at the PCR. The results revealed the presence of three vector species of the An. gambiae complex, of which 409 Anopheles coluzzii, 259 An. gambiae, 5 hybrids (An. coluzzii/An. gambiae) and 4 Anopheles arabiensis in the different agro-ecological zones. The four An. arabiensis were only found in Dassa, a locality in the cotton zone of central Benin. The frequency of distribution of the L1014F allele of the kdr gene varies from 84.48 to 100% in An. gambiae, from 80 to 100% in An. coluzzii and from 0 to 75% in An. arabiensis in the different agro-ecological zones. Moreover, a significant difference is generally observed in the distribution of the L1014F allele (P < 0.05). By comparing in pairs the distribution frequencies of this allele in the two species by agro-ecological zone, only a significant difference is noted in the central cotton and fishery zones (P = 0.0496). CONCLUSION: In summary, even if the data are in small portions, the An. Arabiensis species was found only in central Benin and the L1014F allele of the kdr gene is widespread and seems to fix in all the species recorded in the different agro-ecological zones. This situation amplifies the problem of resistance, which could eventually be a significant obstacle for the malaria vectors control. Similarly, a study of their genetic structure via the L1014F allele is necessary in order to put in place strategies to manage this resistance. These strategies will take into account both the ecology and the genetic diversity of the organisms involved to preserve the effectiveness of pyrethroids, the only insecticides used for the impregnation of mosquito nets.

Neutrophil Metabolic Shift during their Lifecycle: Impact on their Survival and Activation.

Polymorphonuclear neutrophils (PMNs) are innate immune cells, which represent 50% to 70% of the total circulating leukocytes. How PMNs adapt to various microenvironments encountered during their life cycle, from the bone marrow, to the blood plasma fraction, and to inflamed or infected tissues remains largely unexplored. Metabolic shifts have been reported in other immune cells such as macrophages or lymphocytes, in response to local changes in their microenvironment, and in association with a modulation of their pro-inflammatory or anti-inflammatory functions. The potential contribution of metabolic shifts in the modulation of neutrophil activation or survival is anticipated even though it is not yet fully described. If neutrophils are considered to be mainly glycolytic, the relative importance of alternative metabolic pathways, such as the pentose phosphate pathway, glutaminolysis, or the mitochondrial oxidative metabolism, has not been fully considered during activation. This statement may be explained by the lack of knowledge regarding the local availability of key metabolites such as glucose, glutamine, and substrates, such as oxygen from the bone marrow to inflamed tissues. As highlighted in this review, the link between specific metabolic pathways and neutrophil activation has been outlined in many reports. However, the impact of neutrophil activation on metabolic shifts' induction has not yet been explored. Beyond its importance in neutrophil survival capacity in response to available metabolites, metabolic shifts may also contribute to neutrophil population heterogeneity reported in cancer (tumor-associated neutrophil) or auto-immune diseases (Low/High Density Neutrophils). This represents an active field of research. In conclusion, the characterization of neutrophil metabolic shifts is an emerging field that may provide important knowledge on neutrophil physiology and activation modulation. The related question of microenvironmental changes occurring during inflammation, to which neutrophils will respond to, will have to be addressed to fully appreciate the importance of neutrophil metabolic shifts in inflammatory diseases.

The evolutionary fate of heterogeneous gene duplications: A precarious overdominant equilibrium between environment, sublethality and complementation.

Gene duplications occur at a high rate. Although most appear detrimental, some homogeneous duplications (identical gene copies) can be selected for beneficial increase in produced proteins. Heterogeneous duplications, which combine divergent alleles of a single locus, are seldom studied due to the paucity of empirical data. We investigated their role in an ongoing adaptive process at the ace-1 locus in Culex pipiens mosquitoes. We assessed the worldwide diversity of the ace-1 alleles (single-copy, susceptible S and insecticide-resistant R, and duplicated D that pair one S and one R copy), analysed their phylogeography and measured their fitness to understand their early dynamics using population genetics models. It provides a coherent and comprehensive evolutionary scenario. We show that D alleles are present in most resistant populations and display a higher diversity than R alleles (27 vs. 4). Most appear to result from independent unequal crossing-overs between local single-copy alleles, suggesting a recurrent process. Most duplicated alleles have a limited geographic distribution, probably resulting from their homozygous sublethality (HS phenotype). In addition, heterozygotes carrying different HS D alleles showed complementation, indicating different recessive lethal mutations. Due to mosaic insecticide control practices, balancing selection (overdominance) plays a key role in the early dynamics of heterogeneous duplicated alleles; it also favours a high local polymorphism of HS D alleles in natural populations (overdominance reinforced by complementation). Overall, our study shows that the evolutionary fate of heterogeneous duplications (and their long-term role) depends on finely balanced selective pressures due to the environment and to their genomic structure.

Anoxia and glucose supplementation preserve neutrophil viability and function.

Functional studies of human neutrophils and their transfusion for clinical purposes have been hampered by their short life span after isolation. Here, we demonstrate that neutrophil viability is maintained for 20 hours in culture media at 37°C under anoxic conditions with 3 mM glucose and 32 µg/mL dimethyloxalylglycine supplementation, as evidenced by stabilization of Mcl-1, proliferating cell nuclear antigen (PCNA), and pro-caspase-3. Notably, neutrophil morphology (nucleus shape and cell-surface markers) and functions (phagocytosis, degranulation, calcium release, chemotaxis, and reactive oxygen species production) were comparable to blood circulating neutrophils. The observed extension in neutrophil viability was reversed upon exposure to oxygen. Extending neutrophil life span allowed efficient transfection of plasmids (40% transfection efficiency) and short interfering RNA (interleukin-8, PCNA, and Bax), as a validation of effective and functional genetic manipulation of neutrophils both in vitro and in vivo. In vivo, transfusion of conditioned neutrophils in a neutropenic guinea pig model increased bacterial clearance of Shigella flexneri upon colonic infection, strongly suggesting that these conditioned neutrophils might be suitable for transfusion purposes. In summary, such conditioning of neutrophils in vitro should facilitate their study and offer new opportunities for genetic manipulation and therapeutic use.

Prospective study in bullous pemphigoid: association of high serum anti-BP180 IgG levels with increased mortality and reduced Karnofsky score.

BACKGROUND: Bullous pemphigoid (BP) is a subepidermal blistering disease characterized by autoantibodies against the two hemidesmosomal proteins, BP180 (type XVII collagen) and BP230. The multicentre prospective BLISTER (Bullous Pemphigoid Steroids and Tetracyclines) trial randomized 253 patients with BP to compare the benefits and harms between initial treatment with doxycycline or prednisolone. OBJECTIVES: To analyse distinct autoantibody profiles for the prediction of the disease course in a well-characterized cohort of BP sera. METHODS: One hundred and forty-three patients of the BLISTER trial consented to participate in this serological study. Sera taken at baseline were analysed by (i) indirect immunofluorescence, (ii) anti-BP180 NC16A (16th noncollagenous domain) and anti-BP230 enzyme-linked immunosorbent assay and (iii) immunoblotting with various substrates. Results were then linked with clinical parameters including age, Karnofsky score, number of blisters, related adverse events and mortality. RESULTS: Disease activity correlated with immunoglobulin (Ig)G anti-BP180 levels but not with levels of anti-BP230 IgG and anti-BP180 IgE. High levels of both anti-BP180 IgG and anti-BP230 IgG were associated with a low Karnofsky score. The presence of anti-BP230 IgG was more frequent in older patients. Those with higher total IgE serum levels suffered from fewer adverse events. Higher IgG anti-BP180 levels were associated with an increased 1-year mortality rate. CONCLUSIONS: Analysis of the autoantibody profile is not only of diagnostic relevance but may also be helpful in predicting the course of the disease.

Preparation of milk protein concentrates by ultrafiltration and continuous diafiltration: Effect of process design on overall efficiency.

High-milk-protein concentrates (>80% on a dry weight basis) are typically produced by ultrafiltration (UF) with constant-volume diafiltration (DF). To maximize protein retention at a commercial scale, polymeric spiral-wound UF membranes with a molecular weight cut-off (MWCO) of 10 kDa are commonly used. Flux decline and membrane fouling during UF have been studied extensively and the selection of an optimal UF-DF sequence is expected to have a considerable effect on both the process efficiency and the volumes of by-products generated. The objective of this study was to characterize the performance of the UF-DF process by evaluating permeate flux decline, fouling resistance, energy and water consumption, and retentate composition as a function of MWCO (10 and 50 kDa) and UF-DF sequence [3.5×-2 diavolumes (DV) and 5×-0.8DV]. The UF-DF experiments were performed on pasteurized skim milk using a pilot-scale filtration system operated at 50°C under a constant transmembrane pressure of 465 kPa. The results showed that MWCO had no effect on permeate flux for the same UF-DF sequence. Irreversible resistance was also similar for both sequences, whatever the MWCO, suggesting that soluble protein deposition within the pores is similar for all conditions. Despite lower permeate fluxes and greater reversible resistance for the 5×-0.8DV sequence, the overall energy consumption of the 2 UF-DF sequences was similar. However, the 3.5×-2DV sequence required more water for DF and generated larger volumes of permeate to be processed, which will require more membrane area and lead to greater environmental impact. A comparative life cycle assessment should however be performed to confirm which sequence has the lowest environmental impact.

Process efficiency of casein separation from milk using polymeric spiral-wound microfiltration membranes.

Microfiltration is largely used to separate casein micelles from milk serum proteins (SP) to produce a casein-enriched retentate for cheese making and a permeate enriched in native SP. Skim milk microfiltration is typically performed with ceramic membranes and little information is available about the efficiency of spiral-wound (SW) membranes. We determined the effect of SW membrane pore size (0.1 and 0.2 µm) on milk protein separation in total recirculation mode with a transmembrane pressure gradient to evaluate the separation efficiency of milk proteins and energy consumption after repeated concentration and diafiltration (DF). Results obtained in total recirculation mode demonstrated that pore size diameter had no effect on the permeate flux, but a drastic loss of casein was observed in permeate for the 0.2-µm SW membrane. Concentration-DF experiments (concentration factor of 3.0× with 2 sequential DF) were performed with the optimal 0.1-µm SW membrane. We compared these results to previous data we generated with the 0.1-µm graded permeability (GP) membrane. Whereas casein rejection was similar for both membranes, SP rejection was higher for the 0.1-µm SW membrane (rejection coefficient of 0.75 to 0.79 for the 0.1-µm SW membrane versus 0.46 to 0.49 for the GP membrane). The 0.1-µm SW membrane consumed less energy (0.015-0.024 kWh/kg of permeate collected) than the GP membrane (0.077-0.143 kWh/kg of permeate collected). A techno-economic evaluation led us to conclude that the 0.1-µm SW membranes may represent a better option to concentrate casein for cheese milk; however, the GP membrane has greater permeability and its longer lifetime (about 10 yr) potentially makes it an interesting option.

[Sarcoidosis : Dermatological view of a rare multisystem disease]. / Sarkoidose : Dermatologischer Blick auf eine seltene Multisystemerkrankung.

Sarcoidosis is a rare multisystem inflammatory disease of largely unknown etiology. While pulmonary sarcoidosis is the most abundant organ manifestation, involvement of the skin that occurs in up to 30% of patients is the most common extrapulmonary presentation of the disease. Dermatologists therefore play an important role not only for establishing the diagnosis and delineating it from potential differential diagnoses but also for the interdisciplinary care of the patient. The clinical presentation of skin sarcoidosis is manifold, which occasionally aggravates making the final diagnosis. Specific skin lesions (with granulomas) and nonspecific skin manifestations (without granulomas) can be differentiated. Since a variety of organ systems can be affected, multidisciplinary cooperation is mandatory. Therapy of sarcoidosis is difficult; evidence-based studies and therapy guidelines are widely lacking. Our review intends to outline the characteristic clinical presentations of cutaneous sarcoidosis, describe the diagnostic approach and how to assure or exclude extracutaneous manifestations of sarcoidosis, and suggest a therapy algorithm for the treatment of skin sarcoidosis.

Effect of transmembrane pressure control on energy efficiency during skim milk concentration by ultrafiltration at 10 and 50°C.

The efficiency of the ultrafiltration process during skim milk concentration was studied using both dynamic and constant (465 or 672kPa) transmembrane pressure experiments at refrigerated temperature (10°C) and high temperature (50°C). The pilot-scale module was equipped with a 10-kDa polyethersulfone spiral-wound membrane element with a surface area of 2.04m2. Permeation flux, resistance-in-series model, mineral and protein rejection, and energy consumption were studied as a function of temperature and transmembrane pressure applied. Higher permeation flux values were systematically obtained at 50°C. Also, a significant temperature effect was found for calcium rejection, which was lower at 10°C compared with 50°C. Total hydraulic resistance and reversible fouling resistance were higher at 50°C than at 10°C. No change in protein rejection was observed, depending on the operating mode studied. Permeation flux, which was higher at 50°C, had lower pumping energy consumption compared with ultrafiltration at the colder temperature. Also, the low ultrafiltration temperature required a higher total energy consumption to reach the 3.6× retentate compared with ultrafiltration at 50°C. Overall, our study shows that the operating parameters and temperature can be optimized using an energy efficiency ratio.

[Differential diagnosis of oral mucosal erosions and ulcers in children]. / Differenzialdiagnose erosiver und ulzeröser Mundschleimhauterkrankungen im Kindesalter.

BACKGROUND: Oral ulcers and erosions are of great clinical importance because they are common in childhood and adolescence and generally painful. They can be related to harmless conditions, such as recurrent aphthous stomatitis. On the other hand, they can be associated with severe systemic diseases making an early diagnosis and initiation of treatment necessary. OBJECTIVES: We herein focus on the systematic presentation of differential diagnoses of oral ulcers and erosions in pediatric patients and present clues in the history and clinical features that are helpful to establish the diagnosis. CONCLUSIONS: Patient's age at the beginning of the symptoms, differentiation between acute and chronic course, distribution of mucosal lesions, additional involvement of the skin, extracutaneous symptoms, general condition of the patient, comorbidities and medication may be determining factors of the correct diagnosis. In children and adolescents aphthous stomatitis, infections and trauma are the most frequent causes of oral ulcerations or erosions of the mucous membranes.

Improvements in hippocampal-dependent memory and microglial infiltration with calorie restriction and gastric bypass surgery, but not with vertical sleeve gastrectomy.

BACKGROUND: Much recent evidence suggest that obesity and related comorbidities contribute to cognitive decline, including the development of non age-related dementia and Alzheimer's disease. Obesity is a serious threat to public health, and few treatments offer proven long-term weight loss. In fact, bariatric surgery remains the most effective long-term therapy to reduce weight and alleviate other aspects of the metabolic syndrome (MetS). Unlike the demonstrated benefits of caloric restriction to prevent weight gain, few if any studies have compared various means of weight loss on central nervous system function and hippocampal-dependent cognitive processes. DESIGN AND RESULTS: Our studies comprise the first direct comparisons of caloric restriction to two bariatric surgeries (Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG)) on cognitive function. Weight loss following caloric restriction, RYGB and VSG was associated with generalized improvements in metabolic health and hippocampal-dependent learning, as measured in the radial arm maze and spontaneous alternation tests. However, VSG-treated rats exhibited deficits on spatial learning tasks in the Morris water maze. In addition, whereas VSG animals had elevated hippocampal inflammation, comparable to that of obese controls, RYGB and calorie-restricted (pair-fed, PF) controls exhibited an amelioration of inflammation, as measured by the microglial protein ionized calcium binding adaptor molecule 1 (IBA1). We also assessed whether GHR (ghrelin) replacement would attenuate hippocampal inflammation in VSG, as post-surgical GHR levels are significantly reduced in VSG relative to RYGB and PF rats. However, GHR treatment did not attenuate the hippocampal inflammation. CONCLUSION: Although VSG was comparably effective at reducing body weight and improving glucose regulation as RYGB, VSG did not appear to confer an equal benefit on cognitive function and markers of inflammation.

Antimicrobial resistance in eight US hospitals along the US-Mexico border, 2000-2006.

Antimicrobial resistance (AR) is a growing problem worldwide and international travel, cross-border migration, and antimicrobial use may contribute to the introduction or emergence of AR. We examined AR rates and trends along the US-Mexico border by analysing microbiology data from eight US hospitals in three states bordering Mexico. Microbiology data were ascertained for the years 2000-2006 and for select healthcare and community pathogens including, three Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae) and three Gram-positive (Staphylococcus aureus, Enterococcus, Streptococcus pneumoniae) pathogens and 10 antimicrobial-pathogen combinations. Resistance was highest in S. aureus (oxacillin resistance 45·7%), P. aeruginosa (quinolone resistance 22·3%), and E. coli (quinolone resistance 15·6%); six (60%) of the 10 antimicrobial-pathogen combinations studied had a significantly increasing trend in resistance over the study period. Potential contributing factors in the hospital and community such as infection control practices and antimicrobial use (prescription and non-prescription) should be explored further in the US-Mexico border region.

Design of a specific colonic mucus marker using a human commensal bacterium cell surface domain.

Imaging living cells and organs requires innovative, specific, efficient, and well tolerated fluorescent markers targeting cellular components. Such tools will allow proceeding to the dynamic analysis of cells and the adaptation of tissues to environmental cues. In this study, we have identified and synthesized a novel non-toxic fluorescent marker allowing a specific fluorescent staining of the human colonic mucus. Our strategy to identify a molecule able to specifically bind to the human colonic mucus was on the basis of the mucus adhesion properties of commensal bacteria. We identified and characterized the mucus-binding property of a 70-amino acid domain (MUB(70)) expressed on the surface of Lactobacillus strains. The chemical synthesis of MUB(70) was achieved using the human commensal bacterium Lactobacillus reuteri AF120104 protein as a template. The synthesized Cy5-conjugated MUB(70) marker specifically stained the colonic mucus on fixed human, rabbit, and guinea pig tissues. Interestingly, murine tissue was not stained, suggesting significant differences in the composition of the murine colonic mucus. In addition, this marker stained the mucus of living cultured human colonic cells (HT29-MTX) and human colonic tissue explants. Using a biotinylated derivative of MUB(70), we demonstrated that this peptide binds specifically to Muc2, the most abundant secreted mucin, through its glycosylated moieties. Hence, Cy5-MUB(70) is a novel and specific fluorescent marker for mammalian colonic mucus. It may be used for live imaging analysis but also, as demonstrated in this study, as a marker for the diagnosis and the prognosis of colonic mucinous carcinomas.

The effect of vertical sleeve gastrectomy on food choice in rats.

OBJECTIVE: Diets high in fat are implicated in the development and maintenance of obesity, and obese individuals display greater preferences for high-fat foods than do their lean counterparts. Weight-reduction bariatric surgery is associated with changes in food choice. In particular, after Roux-en-Y gastric bypass (RYGB), humans and rodents select or prefer foods that are lower in fat content. We asked whether a bariatric surgical procedure limited to the stomach, vertical sleeve gastrectomy (VSG), causes a similar reduction of fat intake/preference. RESEARCH DESIGN AND METHODS: Rats received VSG or Sham surgery or remained surgically naïve, and were assessed for food preference using three diet-choice paradigms. Using progressive-ratio (PR) and conditioned taste aversion paradigms, we further asked whether surgically induced changes in food choice are secondary to changes in the reward value of food and/or to the formation of a food aversion. Finally, food choice was compared between VSG- and RYGB-operated rats. RESULTS: VSG rats decreased their intake of dietary fat, and shifted their preference toward lower caloric-density foods. This change in food choice was not associated with changes in motivated responding on a PR schedule for either a fat or a carbohydrate food reinforcer. When VSG and RYGB were compared directly, both procedures caused comparable changes in food choice. The conditioned taste aversion paradigm revealed that VSG rats form an aversion to an intra-gastric oil administration whereas RYGB rats do not. CONCLUSIONS: VSG and RYGB, two anatomically distinct bariatric procedures, produce similar changes in food choice.