Effects of the nematode Litylenchus crenatae subsp. mccannii and beech leaf disease on leaf fungal and bacterial communities on Fagus grandifolia (American beech).

Beech leaf disease (BLD) is a newly emerging disease in North America that affects American beech (Fagus grandifolia). It is increasingly recognized that BLD is caused by a subspecies of the anguinid nematode Litylenchus crenatae subsp. mccannii (hereafter L. crenatae), which is likely native to East Asia. How nematode infestation of leaves affects the leaf microbiome and whether changes in the microbiome could contribute to BLD symptoms remain uncertain. In this study, we examined bacterial and fungal communities associated with the leaves of F. grandifolia across nine sites in Ohio and Pennsylvania that were either symptomatic or asymptomatic for BLD and used qPCR to measure relative nematode infestation levels. We found significantly higher levels of infestation at sites visibly symptomatic for BLD. Low levels of nematode infestation were also observed at asymptomatic sites, which suggests that nematodes can be present without visible symptoms evident. Bacterial and fungal communities were significantly affected by sampling site and symptomology, but only fungal communities were affected by nematode presence alone. We found many significant indicators of both bacteria and fungi related to symptoms of BLD, with taxa generally occurring in both asymptomatic and symptomatic leaves, suggesting that microbes are not responsible for BLD but could act as opportunistic pathogens. Of particular interest was the fungal genus Erysiphe, which is common in the Fagaceae and is reported to overwinter in buds-a strategy consistent with L. crenatae. The specific role microbes play in opportunistic infection of leaves affected by L. crenatae will require additional study. IMPORTANCE: Beech leaf disease (BLD) is an emerging threat to American beech (Fagus grandifolia) and has spread quickly throughout the northeastern United States and into southern Canada. This disease leads to disfigurement of leaves and is marked by characteristic dark, interveinal banding, followed by leaf curling and drop in more advanced stages. BLD tends to especially affect understory leaves, which can lead to substantial thinning of the forest understory where F. grandifolia is a dominant tree species. Understanding the cause of BLD is necessary to employ management strategies that protect F. grandifolia and the forests where it is a foundation tree species. Current research has confirmed that the foliar nematode Litylenchus crenatae subsp. mccannii is required for BLD, but whether other organisms are involved is currently unknown. Here, we present a study that investigated leaf-associated fungi and bacteria of F. grandifolia to understand more about how microorganisms may contribute to BLD.

Multidisciplinary Management of Adolescent and Young Adult Patients with Hodgkin Lymphoma.

OPINION STATEMENT: Successful management of adolescent and young adult patients with Hodgkin lymphoma (HL) requires a multidisciplinary approach to care with special attention paid to the unique medical, logistical, and psychosocial challenges faced by this group. The emotional and social changes and big life transitions that occur between the ages of 15 and 39 result in a broad scope of supportive care needs that differ from children or adults in similar circumstances. Currently, care of adolescent and young adult (AYA) patients with HL may be fractured across the pediatric-adult cancer care continuum resulting in this group being less well studied than pediatric or adult patients in general. In order to optimize outcomes, these patients need access to medical oncologists and radiation oncologists, advanced practice providers (APPs), psychologists/social work, financial support services, fertility specialists, survivorship care, and advocates with AYA expertise that can help navigate the healthcare system. A strong AYA support system established early with targeted education and resources may influence treatment compliance and likelihood of long-term follow-up. Surveys of the AYA cancer population have identified areas of opportunity for the healthcare team to collaborate to identify needs, design interventions to meet them, and ultimately develop evidence-based guidelines that will enable us to offer AYAs with HL the quality care they deserve.

Through the Looking Glass: Surveillance Following Colonoscopic Polypectomy of Malignant Polyps.

Introduction Colonoscopic polypectomy is a well-established screening and surveillance modality for malignant colorectal polyps. Following the detection of a malignant polyp, patients are either put on endoscopic surveillance or planned for a surgical procedure. We studied the outcome of colonoscopic excision of malignant polyps and their recurrence rates. Methods We performed a retrospective analysis over a period of five years (2015-2019) of patients who underwent colonoscopy and resection of malignant polyps. Size of polyp, follow-up with tumour markers, CT scan, and biopsy were considered individually for pedunculate and sessile polyps. We analysed the percentage of patients who underwent surgical resection, the percentage of patients who were managed conservatively, and the percentage of recurrence post-excision of malignant polyps. Results A total of 44 patients were included in the study. Of the 44 malignant polyps, most were present in the sigmoid colon at 43% (n=19), with the rectum containing 41% (n=18). The ascending colon accounted for 4.5% (n=2), transverse colonic polyps were 7% (n=3), and the descending colon polyps were 4.5% (n=2). Pedunculated polyps made up 55% (n=24). These were Level 1-3 based on Haggits classification; 14 were Haggits Level 1, eight were Haggits Level 2, and two were Haggits Level 3. The rest were sessile polyps making up 45% (n=20). Based on the Kikuchi classification, these were predominantly SM1 (n=12) and SM2 (n=8). Out of 44 cases, 11% (n=5) underwent surgical resection on follow-up in the form of bowel resection. This included three right hemicolectomies, one sigmoid colectomy, and one low anterior resection. Seven per cent (n=3) underwent endoscopic resection as trans-anal endoscopic mucosal resection (TEMS) and 82% (n=36) of the remaining cases were managed with regular follow-up and surveillance. Conclusions Colonoscopic polypectomy offers excellent benefits in detecting colorectal cancer and treating pre-malignant polyps. Colonoscopic polypectomy provides excellent benefits in colorectal cancer (CRC) detection and treatment of malignant polyps. However, it remains to be seen if post-polypectomy surveillance for low-risk polyp cancers would require a change in surveillance.

Primary Effusion Lymphoma: A Clinicopathologic Perspective.

Primary effusion lymphoma (PEL) is a rare, aggressive B-cell lymphoma that usually localizes to serous body cavities to subsequently form effusions in the absence of a discrete mass. Although some tumors can develop in extracavitary locations, the areas most often affected include the peritoneum, pleural space, and the pericardium. PEL is associated with the presence of human herpesvirus 8 (HHV8), also called the Kaposi sarcoma-associated herpesvirus (KSHV), with some variability in transformation potential suggested by frequent coinfection with the Epstein-Barr virus (EBV) (~80%), although the nature of the oncogenesis is unclear. Most patients suffering with this disease are to some degree immunocompromised (e.g., Human immunodeficiency virus (HIV) infection or post-solid organ transplantation) and, even with aggressive treatment, prognosis remains poor. There is no definitive guideline for the treatment of PEL, although CHOP-like regimens (cyclophosphamide, doxorubicin, vincristine, and prednisone) are frequently prescribed and, given the rarity of this disease, therapeutic focus is being redirected to personalized and targeted approaches in the experimental realm. Current clinical trials include the combination of lenalidomide and rituximab into the EPOCH regimen and the treatment of individuals with relapsed/refractory EBV-associated disease with tabelecleucel.

Characteristics Of Medical Device Shortages In The US, 2006-20.

Shortages of critical medical devices during the COVID-19 pandemic exposed vulnerabilities in device markets. From 2010 to 2019 there were approximately five shortages annually, but that number increased fourfold in the first half of 2020. Although most 2020 shortages were triggered by the pandemic, pre-2020 shortages stemmed from regulatory and enforcement actions related to product quality and manufacturing.

Sex hormones regulate NHE1 functional expression and brain endothelial proteome to control paracellular integrity of the blood endothelial barrier.

BACKGROUND: Sex hormones have been implicated in pH regulation of numerous physiological systems. One consistent factor of these studies is the sodium-hydrogen exchanger 1 (NHE1). NHE1 has been associated with pH homeostasis at epithelial barriers. Hormone fluctuations have been implicated in protection and risk for breaches in blood brain barrier (BBB)/blood endothelial barrier (BEB) integrity. Few studies, however, have investigated BBB/BEB integrity in neurological disorders in the context of sex-hormone regulation of pH homeostasis. METHODS//RESULTS: Physiologically relevant concentrations of 17-ß-estradiol (E2, 294 pM), progesterone (P, 100 nM), and testosterone (T,3.12 nM) were independently applied to cultured immortalized bEnd.3 brain endothelial cells to study the BEB. Individual gonadal hormones showed preferential effects on extracellular pH (E2), 14C-sucrose uptake (T), stimulated paracellular breaches (P) with dependence on functional NHE1 expression without impacting transendothelial resistance (TEER) or total protein expression. While total NHE1 expression was not changed as determined via whole cell lysate and subcellular fractionation experiment, biotinylation of NHE1 for surface membrane expression showed E2 reduced functional expression. Quantitative proteomic analysis revealed divergent effects of 17-ß-estradiol and testosterone on changes in protein abundance in bEnd.3 endothelial cells as compared to untreated controls. CONCLUSIONS: These data suggest that circulating levels of sex hormones may independently control BEB integrity by 1) regulating pH homeostasis through NHE1 functional expression and 2) modifying the endothelial proteome.

Loss of Blood-Brain Barrier Integrity in a KCl-Induced Model of Episodic Headache Enhances CNS Drug Delivery.

Cortical spreading depression (CSD) in the CNS is suggested as a common mechanism contributing to headache. Despite strong evidence for CNS involvement in headache disorders, drug development for headache disorders remains focused on peripheral targets. Difficulty in delivering drugs across the blood-brain barrier (BBB) may partially account for this disparity. It is known, however, that BBB permeability is increased during several CNS pathologies. In this study, we investigated BBB changes in response to KCl-induced CSD events and subsequent allodynia in rats. Cortical KCl injection in awake, freely moving rats produced facial allodynia with peak intensity between 1.5 and 3 h and CSD induction within 0.5-2 h postinjection. Brain perfusion of 14C-sucrose as a marker of BBB paracellular permeability revealed increased leak in the cortex, but not brainstem, beginning 0.5 h post-KCl injection and resolving within 6 h; no changes in tight junction (TJ) proteins occludin or claudin-5 expression were observed. Acute pretreatment with topiramate to inhibit CSD did not prevent the increased BBB paracellular permeability. CNS delivery of the abortive anti-migraine agent sumatriptan was increased in the cortex 1.5 h post-KCl injection. Surprisingly, sumatriptan uptake was also increased in the brainstem following CSD induction, suggesting regulation of active transport mechanisms at the BBB. Together, these results demonstrate the ability of CSD events to produce transient, time-dependent changes in BBB permeability when allodynia is present and to mediate access of clinically relevant therapeutics (i.e., sumatriptan) to the CNS.

Two-stage fungal biopulping for improved enzymatic hydrolysis of wood.

A novel two-stage, whole organism fungal biopulping method was examined for increasing the yield of enzymatic hydrolysis of wood into soluble glucose. Liriodendron tulipifera wood chips (1g) were exposed to liquid culture suspensions of white rot (Ceriporiopsis subvermispora) or brown rot (Postia placenta) fungi and incubated at 28°C, either alone in single-stage 30 day (one fungal species applied) or two-stage 60 day (both fungal species applied in alternative succession) treatments. Fungi grew in all treatments, but did not significantly decrease the percent carbohydrate content of the wood. Two-stage treatments differed significantly in mass loss depending on order of exposure, suggesting additive or inhibitory fungal interactions occurred. Treatments consisting of C. subvermispora followed by P. placenta exhibited 6 ± 0.5% mass loss and increased the yield of enzymatic hydrolysis by 67-119%. This significant hydrolysis improvement suggests that fungal biopulping technologies could support commercial lignocellulosic ethanol production efforts if further developed.