Alveolar macrophage-derived extracellular vesicles inhibit endosomal fusion of influenza virus.

Alveolar macrophages (AMs) and epithelial cells (ECs) are the lone resident lung cells positioned to respond to pathogens at early stages of infection. Extracellular vesicles (EVs) are important vectors of paracrine signaling implicated in a range of (patho)physiologic contexts. Here we demonstrate that AMs, but not ECs, constitutively secrete paracrine activity localized to EVs which inhibits influenza infection of ECs in vitro and in vivo. AMs exposed to cigarette smoke extract lost the inhibitory activity of their secreted EVs. Influenza strains varied in their susceptibility to inhibition by AM-EVs. Only those exhibiting early endosomal escape and high pH of fusion were inhibited via a reduction in endosomal pH. By contrast, strains exhibiting later endosomal escape and lower fusion pH proved resistant to inhibition. These results extend our understanding of how resident AMs participate in host defense and have broader implications in the defense and treatment of pathogens internalized within endosomes.

Normal and Abnormal Appearances of the Ovaries during Assisted Reproduction: Multimodality Imaging Review.

Infertility is a common diagnosis that prompts many couples and individuals to seek assisted reproductive technology (ART) for assistance with conception. These technologies have become increasingly used in the United States in the past several decades, with 326 468 ART cycles performed in 2020, resulting in 75 023 live births. This ubiquity of ART also increases the likelihood that radiologists will encounter both normal and abnormal imaging findings associated with these treatments. Thus, radiologists of all subspecialties should be familiar with the multimodality appearance of the ovaries and pelvis in patients undergoing ART treatments. Furthermore, it is imperative that radiologists understand the appearance expected during different stages of the ART process. During stimulated ovulatory cycles, it is normal and expected for the ovaries to appear enlarged and to contain numerous cystic follicles, often with a small to moderate volume of pelvic free fluid. After oocyte retrieval, hemorrhagic ovarian follicles and a small to moderate volume of blood products in the cul-de-sac can be expected to be seen. Multiple nonemergency and emergency complications are related to ART, many of which can be seen at imaging. The most encountered emergency complications of ART include ovarian hyperstimulation syndrome, ectopic pregnancy, heterotopic pregnancy, multiple gestations, ovarian torsion, and procedural complications related to oocyte retrieval. These complications have important clinical implications, thus necessitating accurate and timely detection by the radiologist and the clinical team. ©RSNA, 2023 Supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Serial Neurologic Assessment in Pediatrics (SNAP): A New Tool for Bedside Neurologic Assessment of Critically Ill Children.

OBJECTIVES: We developed a tool, Serial Neurologic Assessment in Pediatrics, to screen for neurologic changes in patients, including those who are intubated, are sedated, and/or have developmental disabilities. Our aims were to: 1) determine protocol adherence when performing Serial Neurologic Assessment in Pediatrics, 2) determine the interrater reliability between nurses, and 3) assess the feasibility and acceptability of using Serial Neurologic Assessment in Pediatrics compared with the Glasgow Coma Scale. DESIGN: Mixed-methods, observational cohort. SETTING: Pediatric and neonatal ICUs. SUBJECTS: Critical care nurses and patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serial Neurologic Assessment in Pediatrics assesses Mental Status, Cranial Nerves, Communication, and Motor Function, with scales for children less than 6 months, greater than or equal to 6 months to less than 2 years, and greater than or equal to 2 years old. We assessed protocol adherence with standardized observations. We assessed the interrater reliability of independent Serial Neurologic Assessment in Pediatrics assessments between pairs of trained nurses by percent- and bias- adjusted kappa and percent agreement. Semistructured interviews with nurses evaluated acceptability and feasibility after nurses used Serial Neurologic Assessment in Pediatrics concurrently with Glasgow Coma Scale during routine care. Ninety-eight percent of nurses (43/44) had 100% protocol adherence on the standardized checklist. Forty-three nurses performed 387 paired Serial Neurologic Assessment in Pediatrics assessments (149 < 6 mo; 91 ≥ 6 mo to < 2 yr, and 147 ≥ 2 yr) on 299 patients. Interrater reliability was substantial to near-perfect across all components for each age-based Serial Neurologic Assessment in Pediatrics scale. Percent agreement was independent of developmental disabilities for all Serial Neurologic Assessment in Pediatrics components except Mental Status and lower extremity Motor Function for patients deemed "Able to Participate" with the assessment. Nurses reported that they felt Serial Neurologic Assessment in Pediatrics, compared with Glasgow Coma Scale, was easier to use and clearer in describing the neurologic status of patients who were intubated, were sedated, and/or had developmental disabilities. About 92% of nurses preferred to use Serial Neurologic Assessment in Pediatrics over Glasgow Coma Scale. CONCLUSIONS: When used by critical care nurses, Serial Neurologic Assessment in Pediatrics has excellent protocol adherence, substantial to near-perfect interrater reliability, and is feasible to implement. Further work will determine the sensitivity and specificity for detecting clinically meaningful neurologic decline.

Postoperative Urinary Retention Rates after Autofill versus Backfill Void Trial following Total Laparoscopic Hysterectomy: A Randomized Controlled Trial.

STUDY OBJECTIVE: To compare the rate of postoperative urinary retention (POUR) after total laparoscopic hysterectomy (TLH) using the autofill vs the backfill void trial. Secondary objectives were to compare the time to discharge from the recovery room, rate of postoperative urinary tract infection (UTI), perceived bladder condition, the effect of bladder function on life, and patient satisfaction. DESIGN: Randomized controlled trial. SETTING: Single academic medical center. PATIENTS: Women who underwent TLH by conventional laparoscopy or robotic-assisted laparoscopy for benign non-urogynecologic indications. INTERVENTIONS: After TLH, participants were randomized to have an autofill void trial (group A) or a backfill void trial once they were able to ambulate (group B). Failure rate, time to discharge, and UTI rate were assessed. Participants completed the patient perception of bladder condition and the incontinence impact questionnaire-short form questionnaires. Patient satisfaction was assessed. Multiple regression analysis was performed to determine the predictors of POUR. MEASUREMENTS AND MAIN RESULTS: Eighty-two participants completed the study after randomization, 42 in group A and 40 in group B. There were no statistically significant differences in demographic or perioperative outcomes. Seven participants had POUR in group A (16.7%) and 11 in group B (27.5%) (p = .36), respectively. The median time to discharge was 176 minutes for group A (160.5, 255.5) and 218 minutes for group B (180, 265) (p = .01), respectively. There were no statistically significant differences in rate of postoperative UTI (p >.99), patient perception of bladder condition scores (p = .24), incontinence impact questionnaire-short form scores (p = .23), and patient satisfaction scores (p = .26). A stepwise logistic regression analysis did not demonstrate any predictors of POUR. CONCLUSION: Backfill void trial once the participant was able to ambulate was not superior to the autofill void trial with respect to the rate of POUR. The autofill void trial resulted in faster same-day discharge.

Short Time-Scale Sensory Coding in S1 during Discrimination of Whisker Vibrotactile Sequences.

Rodent whisker input consists of dense microvibration sequences that are often temporally integrated for perceptual discrimination. Whether primary somatosensory cortex (S1) participates in temporal integration is unknown. We trained rats to discriminate whisker impulse sequences that varied in single-impulse kinematics (5-20-ms time scale) and mean speed (150-ms time scale). Rats appeared to use the integrated feature, mean speed, to guide discrimination in this task, consistent with similar prior studies. Despite this, 52% of S1 units, including 73% of units in L4 and L2/3, encoded sequences at fast time scales (≤20 ms, mostly 5-10 ms), accurately reflecting single impulse kinematics. 17% of units, mostly in L5, showed weaker impulse responses and a slow firing rate increase during sequences. However, these units did not effectively integrate whisker impulses, but instead combined weak impulse responses with a distinct, slow signal correlated to behavioral choice. A neural decoder could identify sequences from fast unit spike trains and behavioral choice from slow units. Thus, S1 encoded fast time scale whisker input without substantial temporal integration across whisker impulses.

The effects of dietary nitrate on plasma glucose and insulin sensitivity in sheep.

Nitrate (NO3 ¯ ) is an effective non-protein nitrogen source for gut microbes and reduces enteric methane (CH4 ) production in ruminants. Nitrate is reduced to ammonia by rumen bacteria with nitrite (NO2 ¯ ) produced as an intermediate. The absorption of NO2 ¯ can cause methaemoglobinaemia in ruminants. Metabolism of NO3 ¯ and NO2 ¯ in blood and animal tissues forms nitric oxide (NO) which has profound physiological effects in ruminants and has been shown to increase glucose uptake and insulin secretion in rodents and humans. We hypothesized that absorption of small quantities of NO2 ¯ resulting from a low-risk dose of dietary NO3 ¯ will increase insulin sensitivity (SI ) and glucose uptake in sheep. We evaluated the effect of feeding sheep with a diet supplemented with 18 g NO3 ¯ /kg DM or urea (Ur) isonitrogenously to NO3 ¯ , on insulin and glucose dynamics. A glucose tolerance test using an intravenous bolus of 1 ml/kg LW of 24% (w/v) glucose was conducted in twenty sheep, with 10 sheep receiving 1.8% supplementary NO3 ¯ and 10 receiving supplementary urea isonitrogenously to NO3 ¯ . The MINMOD model used plasma glucose and insulin concentrations to estimate basal plasma insulin (Ib ) and basal glucose concentration (Gb ), insulin sensitivity (SI ), glucose effectiveness (SG ), acute insulin response (AIRg) and disposition index (DI). Nitrate supplementation had no effect on Ib (p > .05). The decrease in blood glucose occurred at the same rate in both dietary treatments (SG ; p = .60), and there was no effect of NO3 ¯ on either Gb , SI , AIRg or DI. This experiment found that the insulin dynamics assessed using the MINMOD model were not affected by NO3 ¯ administered to fasted sheep at a low dose of 1.8% NO3 ¯ in the diet.

Fallopian tube perfusion in ex-vivo and in-vivo laparoscopic hysterectomy specimens: potential application for uterine transplantation.

STUDY QUESTION: Is there perfusion to the fallopian tubes in ex-vivo and in-vivo uteri at the time of total laparoscopic hysterectomy (TLH), as observed using laser angiography with indocyanine green (ICG)? SUMMARY ANSWER: The fallopian tubes may have perfusion from the utero-ovarian vasculature alone. WHAT IS KNOWN ALREADY: The fallopian tubes are perfused by the uterine and utero-ovarian vessels. Perfusion can be measured using laser angiography with ICG. STUDY DESIGN, SIZE, DURATION: This prospective pilot cohort study included 15 women, ages 32-59 years old, who underwent TLH with bilateral salpingectomy for benign indications. PARTICIPANTS/MATERIALS, SETTING, METHODS: In five participants, TLH was performed and the utero-ovarian artery was cannulated ex vivo and injected with ICG. The other 10 participants underwent the in-vivo protocol. The mesosalpinx and uterine vessels were transected in the partial protocol. Colpotomy was also performed in the complete protocol. All fallopian tubes were imaged using laser angiography with ICG. The relative fluorescence and the fluorescence intensity ratio (length of fluorescent fallopian tube/total length of fallopian tube) of the fallopian tubes were measured in the ex-vivo and in-vivo protocols, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Ex vivo, the fimbria of the ipsilateral fallopian tube had 47% median relative fluorescence as compared to the contralateral fallopian tube, which had 2.4% median relative fluorescence. In vivo, the post-ICG fluorescence intensity ratios were 0.61 ± 0.40 for the partial protocol, and 0.78 ± 0.30 for the complete protocol, with mean differences of 0.37 (95% CI: 0.23-0.50, P < .0001) and 0.22 (95% CI: 0.12-0.31, P < 0.0001), respectively, between the pre-procedure and the post-ICG fluorescence intensity ratios. Greater than 0.75 fluorescence intensity ratios (i.e. >75% tubal length fluorescence) was seen in 60% of fallopian tubes. LIMITATIONS, REASONS FOR CAUTION: This is a pilot study with a small sample size and pathologic uteri, which would not be appropriate for uterine transplantation. No conclusions can be made regarding the functionality of the fallopian tubes. WIDER IMPLICATIONS OF THE FINDINGS: The fallopian tubes may have perfusion with the utero-ovarian vasculature alone, potentially allowing for future animal studies regarding tubal viability in recipients of uterine-tubal transplants. If successful, human uterine-tubal transplantation may allow for spontaneous conception rather than IVF. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used. S.F., P.F.P., K.A.S. and R.F. have no conflicts of interest to report. M.L.S. is an educational consultant for Medtronic (Dublin, Republic of Ireland) and Applied Medical (Rancho Santa Margarita, CA, USA), as well as a stockholder for SynDaver Labs (Tampa, FL, USA). S.E.Z. is an educational consultant for Applied Medical (Rancho Santa Margarita, CA, USA) and is on the advisory board for AbbVie Inc. (Chicago, IL, USA). TRIAL REGISTRATION NUMBER: Not applicable.

Management, Prevention, and Sequelae of Adhesions in Women Undergoing Laparoscopic Gynecologic Surgery: A Systematic Review.

Surgical adhesions can lead to significant consequences including abdominopelvic pain, bowel obstruction, subfertility, and subsequent surgery. Although laparoscopic surgery is associated with a decreased risk of adhesion formation, methods to further decrease adhesions are warranted. We systematically reviewed literature addressing the management, prevention, and sequelae of adhesions in women undergoing laparoscopic gynecologic surgery. We searched PubMed, EMBASE, EBSCOhost, and Cochrane Central Register of Controlled Trials and found 6566 records. The primary outcome was adhesion formation. The secondary outcomes were abdominopelvic pain, quality of life, subfertility, pregnancy, bowel obstruction, urinary symptoms, and subsequent surgery. After applying inclusion and exclusion criteria, 52 studies remained for qualitative synthesis. Risk of bias assessments were applied independently by 2 authors. There was evidence that Hyalobarrier Gel (Anika Therapeutics, Bedford, MA), HyaRegen NCH Gel (Bilar Medikal, Istanbul, Turkey), Oxiplex/AP Gel (Fziomed, Inc., San Luis Obispo, CA), SprayGel (Confluent Surgical Inc., Waltham, MA), and Beriplast (CSL Behring, LLCm King of Prussia, PA) all decrease the incidence of adhesions. Adept (Baxter, Deerfield, IL) significantly decreased de novo adhesion scores of the posterior uterus. Using an integrated treatment approach to pelvic pain significantly improved pain and quality of life compared with standard laparoscopic treatment. Lastly, Hyalobarrier Gel Endo (Anika Therapeutics, Bedford, MA) placement led to a higher pregnancy rate than no barrier usage. Our findings underscore the need for high-quality trials to evaluate the efficacy of surgical techniques, adhesion barriers, and other treatment modalities on the management and prevention of adhesions and their clinical sequelae. This review was registered on PROSPERO (ID = CRD42017068053).

Chronic infections with viruses or parasites: breaking bad to make good.

Eukaryotic forms of life have been continually invaded by microbes and larger multicellular parasites, such as helminths. Over a billion years ago bacterial endosymbionts permanently colonized eukaryotic cells leading to recognized organelles with a distinct genetic lineage, such as mitochondria and chloroplasts. Colonization of our skin and mucosal surfaces with bacterial commensals is now known to be important for host health. However, the contribution of chronic virus and parasitic infections to immune homeostasis is being increasingly questioned. Persistent infection does not necessarily equate to exhibiting a chronic illness: healthy hosts (e.g. humans) have chronic viral and parasitic infections with no evidence of disease. Indeed, there are now examples of complex interactions between these microbes and hosts that seem to confer an advantage to the host at a particular time, suggesting that the relationship has progressed along an axis from parasitic to commensal to one of a mutualistic symbiosis. This concept is explored using examples from viruses and parasites, considering how the relationships may be not only detrimental but also beneficial to the human host.

Physician Engagement in Improving Operative Supply Chain Efficiency Through Review of Surgeon Preference Cards.

STUDY OBJECTIVE: To reduce operative costs involved in the purchase, packing, and transport of unnecessary supplies by improving the accuracy of surgeon preference cards. STUDY DESIGN: Quality improvement study (Canadian Task Force classification II-3). SETTING: Gynecologic surgery suite of an academic medical center. PARTICIPANTS: Twenty-one specialized and generalist gynecologic surgeons. INTERVENTIONS: The preference cards of up to the 5 most frequently performed procedures per surgeon were selected. A total of 81 cards were distributed to 21 surgeons for review. Changes to the cards were communicated to the operating room charge nurse and finalized. MEASUREMENTS AND MAIN RESULTS: Fourteen surgeons returned a total of 48 reviewed cards, 39 of which had changes. A total of 109 disposable supplies were removed from these cards, at a total cost savings of $767.67. The cost per card was reduced by $16 on average for disposables alone. Three reusable instrument trays were also eliminated from the cards, resulting in savings of approximately $925 in processing costs over a 3-month period. Twenty-two items were requested by surgeons to be available on request but were not routinely placed in the room at the start of each case, at a total cost of $6,293.54. The rate of return of unused instruments to storage decreased after our intervention, from 10.1 to 9.6 instruments per case. CONCLUSIONS: Surgeon preference cards serve as the basis for economic decision making regarding the purchase, storing, packing, and transport of operative instruments and supplies. A one-time surgeon review of cards resulted in a decrease in the number of disposable and reusable instruments that must be stocked, transported, counted in the operating room, or returned, potentially translating into cost savings. Surgeon involvement in preference card management may reduce waste and provide ongoing cost savings.

MyD88 signaling inhibits protective immunity to the gastrointestinal helminth parasite Heligmosomoides polygyrus.

Helminth parasites remain one of the most common causes of infections worldwide, yet little is still known about the immune signaling pathways that control their expulsion. C57BL/6 mice are chronically susceptible to infection with the gastrointestinal helminth parasite Heligmosomoides polygyrus. In this article, we report that C57BL/6 mice lacking the adapter protein MyD88, which mediates signaling by TLRs and IL-1 family members, showed enhanced immunity to H. polygyrus infection. Alongside increased parasite expulsion, MyD88-deficient mice showed heightened IL-4 and IL-17A production from mesenteric lymph node CD4(+) cells. In addition, MyD88(-/-) mice developed substantial numbers of intestinal granulomas around the site of infection, which were not seen in MyD88-sufficient C57BL/6 mice, nor when signaling through the adapter protein TRIF (TIR domain-containing adapter-inducing IFN-ß adapter protein) was also ablated. Mice deficient solely in TLR2, TLR4, TLR5, or TLR9 did not show enhanced parasite expulsion, suggesting that these TLRs signal redundantly to maintain H. polygyrus susceptibility in wild-type mice. To further investigate signaling pathways that are MyD88 dependent, we infected IL-1R1(-/-) mice with H. polygyrus. This genotype displayed heightened granuloma numbers compared with wild-type mice, but without increased parasite expulsion. Thus, the IL-1R-MyD88 pathway is implicated in inhibiting granuloma formation; however, protective immunity in MyD88-deficient mice appears to be granuloma independent. Like IL-1R1(-/-) and MyD88(-/-) mice, animals lacking signaling through the type 1 IFN receptor (i.e., IFNAR1(-/-)) also developed intestinal granulomas. Hence, IL-1R1, MyD88, and type 1 IFN receptor signaling may provide pathways to impede granuloma formation in vivo, but additional MyD88-mediated signals are associated with inhibition of protective immunity in susceptible C57BL/6 mice.

IL-6 controls susceptibility to helminth infection by impeding Th2 responsiveness and altering the Treg phenotype in vivo.

IL-6 plays a pivotal role in favoring T-cell commitment toward a Th17 cell rather than Treg-cell phenotype, as established through in vitro model systems. We predicted that in the absence of IL-6, mice infected with the gastrointestinal helminth Heligmosomoides polygyrus would show reduced Th17-cell responses, but also enhanced Treg-cell activity and consequently greater susceptibility. Surprisingly, worm expulsion was markedly potentiated in IL-6-deficient mice, with significantly stronger adaptive Th2 responses in both IL-6(-/-) mice and BALB/c recipients of neutralizing anti-IL-6 monoclonal Ab. Although IL-6-deficient mice showed lower steady-state Th17-cell levels, IL-6-independent Th17-cell responses occurred during in vivo infection. We excluded the Th17 response as a factor in protection, as Ab neutralization did not modify immunity to H. polygyrus infection in BALB/c mice. Resistance did correlate with significant changes to the associated Treg-cell phenotype however, as IL-6-deficient mice displayed reduced expression of Foxp3, Helios, and GATA-3, and enhanced production of cytokines within the Treg-cell population. Administration of an anti-IL-2:IL-2 complex boosted Treg-cell proportions in vivo, reduced adaptive Th2 responses to WT levels, and fully restored susceptibility to H. polygyrus in IL-6-deficient mice. Thus, in vivo, IL-6 limits the Th2 response, modifies the Treg-cell phenotype, and promotes host susceptibility following helminth infection.

Innate and adaptive type 2 immune cell responses in genetically controlled resistance to intestinal helminth infection.

The nematode Heligmosomoides polygyrus is an excellent model for intestinal helminth parasitism. Infection in mice persists for varying lengths of time in different inbred strains, with CBA and C57BL/6 mice being fully susceptible, BALB/c partially so and SJL able to expel worms within 2-3 weeks of infection. We find that resistance correlates not only with the adaptive Th2 response, including IL-10 but with activation of innate lymphoid cell and macrophage populations. In addition, the titer and specificity range of the serum antibody response is maximal in resistant mice. In susceptible strains, Th2 responses were found to be counterbalanced by IFN-γ-producing CD4(+) and CD8(+) cells, but these are not solely responsible for susceptibility as mice deficient in either CD8(+) T cells or IFN-γ remain unable to expel the parasites. Foxp3(+) Treg numbers were comparable in all strains, but in the most resistant SJL strain, this population does not upregulate CD103 in infection, and in the lamina propria the frequency of Foxp3(+)CD103(+) T cells is significantly lower than in susceptible mice. The more resistant SJL and BALB/c mice develop macrophage-rich IL-4Rα-dependent Type 2 granulomas around intestinal sites of larval invasion, and expression of alternative activation markers Arginase-1, Ch3L3 (Ym1) and RELM-α within the intestine and the peritoneal lavage was also strongly correlated with helminth elimination in these strains. Clodronate depletion of phagocytic cells compromises resistance of BALB/c mice and slows expulsion in the SJL strain. Thus, Type 2 immunity involves IL-4Rα-dependent innate cells including but not limited to a phagocyte population, the latter likely involving the action of specific antibodies.

Using our understanding of interactions between helminth metabolism and host immunity to target worm survival.

Helminths can adapt to environmental conditions in the host, utilising anaerobic processes like fermentation and malate dismutation to produce energy from carbohydrate. Although targeting carbohydrate metabolism is an established therapeutic strategy to combat helminth infection, questions remain over the metabolic pathways they employ as adults to survive and evade host immunity. Helminths also use amino acid, polyunsaturated fatty acid (PUFA), and cholesterol metabolism, a possible strategy favouring the production of immunomodulatory compounds that may influence survival in the host. Here, we discuss the significance of these differing metabolic pathways and whether targeting of helminth metabolic pathways may allow for the development of novel anthelmintics.

Adenomyoepithelioma of the Breast: Radiologic-Pathologic Correlation and Management.

Adenomyoepithelioma (AME) is a rare, usually benign breast neoplasm with low potential for malignant transformation. Imaging features are nonspecific and overlap with other benign and malignant breast lesions. On mammography, AME most often presents as a mass, usually oval in shape, with variable reported margins. Less commonly, AME can present mammographically as an asymmetry or can be mammographically occult. Associated calcifications are uncommon. On US, AME is usually seen as a hypoechoic oval mass, but it can also manifest as a complex cystic and solid mass. On US, the majority of AME have noncircumscribed margins (indistinct, angular, or microlobulated). Internal vascularity is usually present, and posterior enhancement can be seen. Although there is limited literature on MRI features, the most frequent finding is an irregular mass with washout kinetics; T2 hyperintensity can be observed. These nonspecific and often suspicious imaging features usually merit biopsy. On histologic analysis, AME is characterized by a biphasic proliferation of myoepithelial and epithelial cells. Pathologic diagnosis can be difficult due to the variety of histologic features of AME and heterogeneity in these tumors, especially when sampling is limited, such as in core needle biopsies. Wide local surgical excision of AME is recommended due to potential for recurrence and malignant transformation.

Chryseobacterium angstadtii sp. nov., isolated from a newt tank.

As part of an undergraduate microbiology course, a yellow-orange-pigmented, Gram-staining negative, rod-shaped, non-motile bacterial strain was isolated from a glass tank housing several red-spotted newts (Notophthalmus viridescens). The sequence of the 16S rRNA gene of this strain, designated KM(T), was 97.4-98.0 % similar to those of the type strains of Chryseobacterium luteum, C. shigense and C. vrystaatense, while the similarity levels for protein-coding genes were less than 94.7 % for rpoB, less than 92.1 % for groEL and less than 87.1 % for gyrB. These values are lower than for many other established distinct species. Polyphasic characterization and comparison to these relatives revealed that strain KM(T) was similar to other Chryseobacterium strains in that it contained MK-6 as its major respiratory quinone and phosphatidylethanolamine as the most abundant polar lipid, produced flexirubin-type pigments, oxidase and catalase and primarily contained the fatty acids iso-C15 : 0, iso-C17 : 1ω9c, iso-C17 : 0 3-OH and summed feature 3 (comprising C16 : 1ω6c and/or C16 : 1ω7c). Based on the results of this study, strain KM(T) represents a novel species, for which the name Chryseobacterium angstadtii sp. nov. is proposed. The type strain is KM(T) ( = ATCC BAA-2160(T) = NRRL B-59516(T) = KCTC 23297(T)).

Chronic helminth infection promotes immune regulation in vivo through dominance of CD11cloCD103- dendritic cells.

Gastrointestinal helminth infections are extremely prevalent in many human populations and are associated with downmodulated immune responsiveness. In the experimental model system of Heligmosomoides polygyrus, a chronic infection establishes in mice, accompanied by a modulated Th2 response and increased regulatory T cell (Treg) activity. To determine if dendritic cell (DC) populations in the lymph nodes draining the intestine are responsible for the regulatory effects of chronic infection, we first identified a population of CD11c(lo) nonplasmacytoid DCs that expand after chronic H. polygyrus infection. The CD11c(lo) DCs are underrepresented in magnetic bead-sorted preparations and spared from deletion in CD11c-diptheria toxin receptor mice. After infection, CD11c(lo) DCs did not express CD8, CD103, PDCA, or Siglec-H and were poorly responsive to TLR stimuli. In DC/T cell cocultures, CD11c(lo) DCs from naive and H. polygyrus-infected mice could process and present protein Ag, but induced lower levels of Ag-specific CD4(+) T cell proliferation and effector cytokine production, and generated higher percentages of Foxp3(+) T cells in the presence of TGF-ß. Treg generation was also dependent on retinoic acid receptor signaling. In vivo, depletion of CD11c(hi) DCs further favored the dominance of the CD11c(lo) DC phenotype. After CD11c(hi) DC depletion, effector responses were inhibited dramatically, but the expansion in Treg numbers after H. polygyrus infection was barely compromised, showing a significantly higher regulatory/effector CD4(+) T cell ratio compared with that of CD11c(hi) DC-intact animals. Thus, the proregulatory environment of chronic intestinal helminth infection is associated with the in vivo predominance of a newly defined phenotype of CD11c(lo) tolerogenic DCs.

Molecular Breast Imaging in the Screening Setting.

Early detection of breast cancer through screening mammography saves lives. However, the sensitivity of mammography for breast cancer detection is reduced in women with dense breast tissue. Imaging modalities for supplemental breast cancer screening include MRI, whole breast US, contrast-enhanced mammography, and molecular breast imaging (MBI). Molecular breast imaging with 99mTc-sestamibi is a functional imaging test to identify metabolically active areas in the breast with positioning analogous to mammography. Since 2011, there have been six large, published studies of screening MBI as a supplement to mammography involving over 6000 women from four different institutions. A multicenter, prospective clinical trial of 3000 women comparing breast cancer detection using screening digital breast tomosynthesis alone or in combination with MBI recently completed enrollment. This review focuses on the current evidence of MBI use for supplemental breast cancer screening, the strengths and limitations of MBI, and recent technological advances.