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Human milk oligosaccharides (HMOs) ensure proper infant gut microbiome establishment. Isolate studies have revealed the genetic basis for HMO metabolism, but they exclude the possibility of HMO assimilation via synergistic interactions involving multiple organisms. Here, we investigated microbiome responses to 2'-fucosyllactose (2’FL), a prevalent HMO and infant formula additive, by establishing individualized microbiomes using fecal samples from three different infants as the inocula. Bifidobacterium breve, a prominent member of infant microbiomes, typically cannot metabolize 2’FL. Using metagenomic data, we predicted that extracellular fucosidases encoded by co-existing members such as Ruminococcus gnavus initiate 2’FL breakdown, thus critical for B. breve’s growth. Using both targeted co-cultures and by supplementation of R. gnavus into one microbiome, we show that R. gnavus can promote extensive growth of B. breve through the release of lactose from 2’FL. Overall, microbiome cultivation combined with genome-resolved metagenomics demonstrated that HMO utilization can vary with an individual’s microbiome.

Human milk oligosaccharides (HMOs) ensure proper infant gut microbiome establishment. Isolate studies have revealed the genetic basis for HMO metabolism, but they exclude the possibility of HMO assimilation via synergistic interactions involving multiple organisms. Here, we investigated microbiome responses to 2’-fucosyllactose (2’FL), a prevalent HMO and infant formula additive, by establishing individualized microbiomes using fecal samples from three different infants as the inocula.Bifidobacterium breve, a prominent member of infant microbiomes, typically cannot metabolize 2’FL. Using metagenomic data, we predicted that extracellular fucosidases encoded by co-existing members such asRuminococcus gnavusinitiate 2’FL breakdown, thus critical forB. breve’sgrowth. Using both targeted co-cultures and by supplementation ofR. gnavusinto one microbiome, we show thatR. gnavuscan promote extensive growth ofB. brevethrough the release of lactose from 2’FL. Overall, microbiome cultivation combined with genome-resolved metagenomics demonstrated that HMO utilization can vary with an individual’s microbiome.

Management of symptomatic ureteropelvic junction (UPJ) obstruction with hydronephrosis and discordant Tc-99 MAG-3 renal scintigraphy is challenging. Here we describe long-term outcomes of patients who underwent robot-assisted laparoscopic pyeloplasty for the correction of symptomatic UPJ obstruction with discordant pre-operative Tc-99m mercaptoacetyltriglycine (MAG-3) renal scintigraphy.Patients undergoing robot-assisted laparoscopic pyeloplasty for symptomatic UPJ obstruction at a single academic center from 2009 to 2021 were retrospectively reviewed. Patients were categorized into three groups with varying degrees of obstruction based on pre-operative MAG-3 imaging: Group 1- no obstruction (Lasix T1/2 clearance10 minutes), Group 2- equivocal obstruction (Lasix T1/2 clearance 10-20 minutes), and Group 3: obstruction (Lasix T1/2 clearance20 minutes. Pyeloplasty success was defined as resolution of symptoms and improvement/stable CT imaging or MAG-3 scintigraphy. Failure was defined as persistence of symptoms with either obstruction on functional imaging, worsening hydronephrosis, or subsequent intervention.125 cases were identified, with a median patient age of 35 years. Dismembered pyeloplasty technique was performed in 98.4% of cases. Median pre-operative split renal function on MAG-3 scintigraphy was the only statistically significant (p = 0.003) difference in pre-operative characteristics between the three groups. There were 15 post-operative complications, with a rate of Clavien-Dindo grade 3 or higher complications of 4.8%. Overall pyeloplasty success was 92.8%, with success rates of 100% (15/15) and 97% (32/33) in the no obstruction and equivocal obstruction groups, respectively. Median time to pyeloplasty failure was 20.4 months.Robot-assisted laparoscopic pyeloplasty is a safe and effective surgical intervention for correcting UPJ obstruction. Patients with symptoms of UPJ obstruction and discordant functional imaging studies demonstrate similar or improved success rates after pyeloplasty when compared to patients with documented high-grade obstruction. Based on these findings pre-operative renal scan may not be reliable in appropriate selection of candidacy for successful pyeloplasty.

Clinical use of various forms of immunotherapeutic drugs in glioblastoma (GBM), has highlighted severe T cell dysfunction such as exhaustion in GBM patients. However, reversing T cell exhaustion using immune checkpoint inhibitors in GBM clinical trials has not shown significant overall survival benefit. Phenotypically, CD8+ T cells with downregulated CD28 coreceptors, low CD27 expression, increased CD57 expression, and telomere shortening are classified as senescent T cells. These senescent T cells are normally seen as part of aging and also in many forms of solid cancers. Absence of CD28 on T cells leads to several functional irregularities including reduced TCR diversity, incomplete activation of T cells, and defects in Ag-induced proliferation. In the context of GBM, presence and/or function of these CD8+CD28– T cells is unknown. In this clinical correlative study, we investigated the effect of aging as well as tumor microenvironment on CD8+ T cell phenotype as an indicator of its function in GBM patients. We systematically analyzed and describe a large population of CD8+CD28– T cells in both the blood and tumor-infiltrating lymphocytes of GBM patients. We found that phenotypically these CD8+CD28– T cells represent a distinct population compared with exhausted T cells. Comparative transcriptomic and pathway analysis of CD8+CD28– T cell populations in GBM patients revealed that tumor microenvironment might be influencing several immune related pathways and thus further exaggerating the age associated immune dysfunction in this patient population.

The Lesser Pacific Striped Octopus,Octopus chierchiae, is a small iteroparous octopus known to inhabit intertidal regions of the Pacific coast of Central America. Many details about its life history and ecology remain unknown. For apparently rare and delicate animals such asO. chierchiae, non-extractive sampling methods are necessary to study individuals and populations over time. After photographically documenting the physical development of 25 octopuses from hatching, we have concluded thatO. chierchiaehas individually unique stripe configurations that remain constant throughout their post-hatchling lifetimes. Furthermore, using photographs taken of animals in captivity on different dates over many months, we show that untrained volunteers can accurately identify whether or not a pair of images depicts the same individual octopus. These results demonstrate that laboratory-reared individuals could be identified via photographs taken at different points in their lifetimes, which suggests wild individuals can also be recognized and observed for longitudinal field studies. In addition, our results imply potential for photoidentification and community science to be used as non-extractive, non-intrusive sampling methods for future studies of wildO. chierchiae.

INTRODUCTION AND OBJECTIVE:Diabetes (DM) affects 34.2 million Americans.1 Diabetic bladder dysfunction is thought to affect approximately 25-50% of patients with Type 2 diabetes and is classically ...

Objective: The objective is to compare robotic sacral colpopexy (RSC) utilizing autologous fascia lata with RSC with synthetic mesh in the treatment of pelvic organ prolapse (POP). Methods: We perf...

Background and Hypothesis: Glioblastoma (GBM) is the most common primary brain tumor in adults and has a median overall survival of 20.6 months. Intracranial location, infiltrative growth with near 100% recurrence and the blood brain barrier are challenges which make treating GBM difficult. CD8+ T cells (CTLs) are largely responsible for mediating anti-tumor responses and thus, are an endpoint to most immunotherapies. However, the immunosuppressive tumor microenvironment (TME) hampers T cell effectiveness and causes exhaustion and senescence. Senescent CTLs (CD28-CD57+) can result from DNA damage which causes loss of CD28. Lack of CD28 renders CTLs insensitive to immune signals and result in loss of cytotoxic functions. Thus, we hypothesize that CTLs have lost CD28 expression and are becoming senescent in the TME of GBM patients. Experimental Design or Project Methods: CD8 and CD28 RNA expression data was pulled from TCGA in glioma and normal brain patients and a Pearson’s correlation was conducted. Lymphocytes were isolated from patient tumor brain and blood and using flow cytometry, CD3+ CD8+ T cells were identified and stained for CD28, CD57, PD-1, and TIM-3. Results: RNA sequencing data from TCGA database on CD8 and CD28 expression showed a negative correlation in GBM patients compared to normal patients. Majority of CD8+ lymphocytes from patient brain had lost CD28+ expression compared to blood. Conclusion and Potential Impact: The increased senescent T cell population in GBM suggests that the TME has a mechanism for cytotoxic T cell immunosuppression. Preventing CD8+ T cell senescence in GBM can improve current immunotherapies by promoting activation of tumor infiltrating lymphocytes.

The cultivars Sarracenia 'Hummer's Okee Classic', Sarracenia 'Super Green Giant', Sarracenia 'Harvest of Gold', Sarracenia 'Hummer's Hammerhead', Dionaea 'Jaws', Sarracenia 'Golden-Red Jubilee', Sarracenia 'Green Rosette', Sarracenia 'John's Autumnal Splendor' are descrbed.

The cultivars Utricularia 'Cthulhu', Dionaea 'Dentate Traps', Dionaea Dentate Traps Group, Sarracenia 'Imhotep', Utricularia 'Lavinia Whateley', Utricularia 'Mrs. Marsh', Pinguicula 'Pirouette', Dionaea 'Sawtooth', Utricularia 'Yog-Sothoth' are described.

SummaryDue to the high risk of thrombocytopenia and haemorrhage, thrombotic complications have received little attention in patients with acute myeloid leukemia (AML). Furthermore, the predictive role of cytogenetics on venous thromboembolism (VTE) has largely been ignored. This study aimed to evaluate the incidence, risk factors, and prognostic aspects of VTE in AML. A total of 811 consecutive patients with AML were enrolled and analysed retrospectively. Cox time-dependent covariate regression analysis was used to identify the significant predictors of VTE development. To minimise potential confounding factors, we used propensity-score matching to compare overall survival between patients with and without VTE. The six-month and one-year cumulative incidences of VTE were 3.1 % (95 % confidence interval [CI], 2.0–4.7) and 3.9 % (95 % CI, 2.6–5.7), respectively. Of the 26 cases of VTE, 22 (85 %) developed within 6 months of leukemia diagnosis and 13 (50 %) were catheter-related. In multivariate analysis, advanced age (≥ 65 years) (hazard ratio [HR], 2.70; p = 0.03) and increasing cytogenetic risk (common HR, 1.84; p = 0.05) were independent predictors of VTE. There was no significant association between VTE development and decreased survival (p = 0.32 for matched analysis). Advanced age and increasing cytogenetic risk, well-known predictors for clinical outcome in AML, were also independent risk factors of VTE development. Our results suggest that VTE does not hold prognostic implications for AML.

Introduction: The esophagus may be affected by several infective agents, which cause mucosa alterations of various degree, and which can determine either light symptons or critical clinical problems with a high mortality risk. These diseases very often affect patients with reduced immunocompetence. Some of the infectious agents most frequently involved in esophageal infections are Herpes virus, Candida, CMV, HIV. Infectious esophagitis from HPVs are rare in the western countries. The greater number of registered cases have been discovered in the East. Hypotesis is that HPV is a possible etiologic agent in esophageal carcinogenesis, most probaby acting synergistically with physical, chemical, and/or nutritional factors in some high-risk areas of China. Although there are specific endoscopic aspect for infectious esophagitis from different agents, it is difficult to make a differential diagnosis and therefore biopsies, cultures and brushing have a particular importance. The bioptic area is a critical point for histological diagnosis of infectious oesophagitis. Infact, in case of suspected infection from herpes virus, the biopsies must be made on the mucosa surrounding the ulcerative lesion, whereas, for the cytomegalovirus, the specimen must be obteined from the ulcerative crater. Other important procedure, in case of supposed infectiouse disease, is culture, especially with the “shell vial” technique. Epidemiological and experimental evidences suggest the possibility that HPV infection increases the cancer risk for the oral cavity, pharynx and upper aerodigestive tract. However, histologic changes, suggesting HPV infection, are occasionally found adjacent to squamous cell carcinoma or in squamous papilloma of the esophagus, but the relationship between HPV infection and benign and malignant squamous lesions of the esophagus is not yet clear. It is important to differenziate infective esophagitis from gastroesophageal reflux esophagitis in order to perform an up-to-date treatment. Clinical Case: A 25 year old woman was hospitalized in the Federico II University Dept. of General Surgery for arising of retrosternal pain, odynophagia and dysphagia, both for solids and liquids. These symptoms had begun six days before admission. Bioumoral routine tests showed no abnormalities. No pathognomonic symptoms for gastroesophageal reflux nor caustic assumption was referred. The esophago-gastro-duodenoscopy showed, in midium esophagus, a large and deep ulcerative lesion, which involved the whole lumen between 26 and 30 cm. The lesion was thickened and covered by fibrin. Several bioptic tests were performed: IgG anti-varicella-zoster virus, anti-herpes simplex virus, anti-Epstein-Barr-vca were positive. The anti-HIV 1-2 test was negative. No lymphocytic alteration was observed. The histological diagnosis was “active chronic inflammatory infiltration and fibrinoleukocyte exudate”, which is direct sign of ulcerative lesion. Cytologic changes of coilocytic type (giving evidence for HPV infection) were observed. Examination of oral cavity, pharynx and upper respiratory tract gived no evidence of lesions by HPV or other causes. The patient received therapy consisting in mucosal protectives (sucralphate) and Total Parenteral Nutrition. At EGDS, performed two weeks later, the lesion appeared completely healed. References 1. Chang F., Syrjanen S., Shen Q., et al. Evaluation of HPV, CMV, HSV and EBV in esophageal squamous cell carcinomas fom a high-incidence area of China. Anticancer Res 2000 20(5C): 3935-40. 2. Chen L., Yang L., Sun Z. et al. Detection of human papillomaviral infection on Kazakh patients with esophageal squamous cell carcinoma in Xinjiang Chinese Journal of Clinical Oncology 2009; 6 (1): 64-67 3. de Villiers E.M., Lavergne D., Chang F., et al. An interlaboratory study to determine the presence of human papillomaviruses DNA in esophageal carcinoma from China. Int J Cancer 1999; 81(2): 225-8. 4. Franceschi S., Munoz N., Bosch XF et al. Human papillomavirus and cancers of the upper aerodigestive tract: a review of epidemiological and experimental evidence. Cancer Epidemiol Biomarkers Prev 1996; 5 (7): 567-75. 5. Kamangar F., Qiao Y.L., Schiller J.T. et al. Human papillomavirus serology and the risk of esophageal and gastric cancers: Results from a cohort in a high-risk region in China. International Journal of Cancer 2006; 119 (3): 579-584