Manganese Oxidation States in Volcanic Soils across Annual Rainfall Gradients.

Manganese (Mn) exists as Mn(II), Mn(III), or Mn(IV) in soils, and the Mn oxidation state controls the roles of Mn in numerous environmental processes. However, the variations of Mn oxidation states with climate remain unknown. We determined the Mn oxidation states in highly weathered bulk volcanic soils (primary minerals free) across two rainfall gradients covering mean annual precipitation (MAP) of 0.25-5 m in the Hawaiian Islands. With increasing MAP, the soil redox conditions generally shifted from oxic to suboxic and to anoxic despite fluctuating at each site; concurrently, the proportions of Mn(IV) and Mn(II) decreased and increased, respectively. Mn(III) was low at both low and high MAP, but accumulated substantially, up to 80% of total Mn, in soils with prevalent suboxic conditions at intermediate MAP. Mn(III) was likely hosted in Mn(III,IV) and iron(III) oxides or complexed with organic matter, and its distribution among these hosts varied with soil redox potentials and soil pH. Soil redox conditions and rainfall-driven leaching jointly controlled exchangeable Mn(II) in soils, with its concentration peaking at intermediate MAP. The Mn redox chemistry was at disequilibrium, with the oxidation states correlating with long-term average soil redox potentials better than with soil pH. The soil redox conditions likely fluctuated between oxic and anoxic conditions more frequently at intermediate than at low and high MAP, creating biogeochemical hot spots where Mn, Fe, and other redox-sensitive elements may be actively cycled.

A Rare Instance of Chronic Masson's Tumor Presenting in the External Auditory Meatus and Surgical Plan: A Case Report.

Intravascular papillary endothelial hyperplasia (IPEH), or Masson's tumor, is a rare and benign proliferation of endothelial cells typically of vascular origin. Common locations of Masson's tumor include the head, neck, orbit, lip, pharynx, and mandible. It is typically seen in middle-aged adult life and females. Possible differential diagnoses include hemangioma, benign vascular formation, angiosarcoma, and neurofibromatosis. The exact pathophysiology of Masson's tumor is currently unknown. We present the case of a middle-aged 47-year-old male with a pure type of Masson's tumor presenting with pedunculated, malleable lesions across the posterior scalp and circumferential neck, on the pinna of the right ear, and within the right external auditory meatus. The lesions within the right external auditory meatus caused conductive hearing loss. The plan is a complete surgical excision without wide margins. The patient was referred to an ear, nose, and throat (ENT) surgeon due to the complicated location of the lesion within the external auditory meatus. This case serves as a differential diagnosis of conductive hearing loss complicated by Masson's tumor.

Third dose of COVID-19 mRNA vaccine appears to overcome vaccine hyporesponsiveness in patients with cirrhosis.

BACKGROUND & AIMS: Cirrhosis is associated with immune dysregulation and hyporesponsiveness to several vaccines including those against COVID-19. Our aim was to compare outcomes between patients with cirrhosis who received 3 doses of either the Pfizer BNT162b2 mRNA or Moderna mRNA-1273 vaccines to a propensity-matched control group of patients at similar risk of infection who received 2 doses. METHODS: This was a retrospective cohort study of patients with cirrhosis who received 2 or 3 doses of a COVID-19 mRNA vaccine at the Veterans Health Administration. Participants who received 3 doses of the vaccine (n = 13,041) were propensity score matched with 13,041 controls who received 2 doses, and studied between July 18, 2021 and February 11, 2022, when B.1.617.2 (delta) and B.1.1.529 (omicron) were the predominant variants. Outcomes were aggregated as all cases with COVID-19, symptomatic COVD-19, with at least moderate COVID-19, or severe or critical COVID-19. RESULTS: Receipt of the third dose of a COVID-19 mRNA vaccine was associated with an 80.7% reduction in COVID-19 (95% CI 39.2-89.1, p <0.001), an 80.4% reduction in symptomatic COVID-19, an 80% reduction in moderate, severe or critical COVID-19, (95% CI 34.5-87.6%, p = 0.005), a 100% reduction in severe or critical COVID-19 (95% CI 99.2-100.0, p = 0.01), and a 100% reduction in COVID-19-related death (95% CI 99.8-100.0, p = 0.007). The magnitude of reduction in COVID-19 was greater with the third dose of BNT 162b2 than mRNA-1273 and among participants with compensated rather than decompensated cirrhosis. CONCLUSIONS: Administration of a third dose of a COVID-19 mRNA vaccine was associated with a more significant reduction in COVID-19 in patients with cirrhosis than in the general population, suggesting that the third dose can overcome vaccine hyporesponsiveness in this population. LAY SUMMARY: Cirrhosis is associated with decreased responsiveness to several vaccines, including those against COVID-19. In this study of 26,082 participants with cirrhosis during the delta and omicron surge, receipt of the third dose of the vaccine was associated with an 80% reduction in COVID-19, a 100% reduction in severe/critical COVID-19, and a 100% reduction in COVID-19-related death. These findings support the importance of a third dose of mRNA vaccine among patients with cirrhosis.

Foliar ẟ15N patterns in legumes and non-N fixers across a climate gradient, Hawai'i Island, USA.

Recent studies from the Hawaiian Islands showed that pedogenic thresholds demarcate domains in which rock-derived nutrient dynamics remain similar across wide variations in rainfall. These thresholds appear related to certain aspects of N cycling, but the degree to which they correspond to patterns of biological N fixation (BNF)-the dominant input of N into less-managed ecosystems-remains unclear. We measured aboveground plant biomass, foliar nutrient concentrations, and foliar δ15N along a climate gradient on ~ 150,000-year-old basaltic substrate to characterize foliar N sources and spatially relate them to soil nutrients. Patterns in legume δ15N correspond to known pedogenic thresholds along the rainfall gradient, with low δ15N values (~ 0 to - 2‰) occurring in the dry, biologically inactive domain and the wet, highly weathered domain. Elevated δ15N in the middle, fertile domain suggests a greater reliance of legumes on soil N where it has accumulated over time. Non-legume face N deficiencies throughout most of the gradient while legumes maintain low C:N ratios via symbiotic BNF. However, legume abundance declines outside the fertile domain, limiting ecosystem N inputs. Breakpoints in legume δ15N data suggest that P (and potentially other nutrients) limits BNF and, by extension, legume abundance in wet region. Nutrients may also constrain legume abundance in the dry domain, but pedogenic effects could not be isolated from climatic constraints at the dry sites. We conclude that pedogenic thresholds defined by climate can be informative of foliar δ15N patterns in cases where legumes are not directly constrained by climate, land use, or other external factors.

Nitrogen dynamics along a climate gradient on geologically old substrate, Kaua'i, Hawai'i.

We evaluated N dynamics on a climate gradient on old (> 4 million year) basaltic substrate on the Island of Kaua'i, Hawai'i, to evaluate the utility of pedogenic thresholds and soil process domains for understanding N cycling in terrestrial ecosystems. Studies of nitrogen dynamics on the climate gradient on a younger basaltic substrate (~ 150,000 year) had found a good match between soil process domains and N cycling processes. Here we measured net N mineralization and nitrification by incubation, and δ15N of total soil N, to determine whether the soil process domains on the older gradient were equally useful for interpreting N cycling and thereby to explore the general utility of the approach. Net N mineralization varied from 0 to 1.7 mg kg-1 d-1 across the old Kaua'i gradient, and δ15N varied from + 3 to + 11 ο/οο, both ranges similar to those on the younger substrate. However, while the pattern of variation with climate was similar for δ15N, the highest rates of mineralization on the old gradient occurred where forests were dominated by the native N fixer Acacia koa. This occurred in sites wetter than the process domain associated with high net N mineralization on the gradient on younger substrate. We conclude that soil process domains based on rock-derived nutrients are not always useful for evaluating N dynamics, especially where the distribution of biological N fixers is controlled by factors other than rock-derived nutrients.

Myoepithelial carcinoma or epithelioid sarcoma - A rare diagnosis with poor prognosis. A case report and review of literature.

INTRODUCTION: Myoepithelial carcinoma and proximal-type epithelioid sarcoma of the vulva are two rare malignancies with known aggressive behavior. In addition to a similar clinical course, these two disease entities also have significant histologic and pathologic overlap. Given the rarity of these malignancies, there is limited literature on the appropriate treatment regimen. Nevertheless, there is a consensus that early surgical resection is beneficial in both cases. PRESENTATION: We present a case of a patient who was initially diagnosed with myoepithelial carcinoma of the vulva with a differential later expanded to include possible epithelioid sarcoma. DISCUSSION: We demonstrate the importance in early identification of a SMARCB1 deficiency. Additionally, we suggest an appropriate treatment regimen for these patients going forward. Specifically, we encourage consideration of bilateral superficial and deep inguinal lymphadenectomies. Furthermore, sarcoma based chemotherapy regimens in the appropriate clinical setting may be beneficial in treating SMARCB1 deficient tumors. Additionally, there are now clinical trials involving EZH2 Inhibitors which may offer benefit for similar patients going forward. CONCLUSION: This case highlights the difficulty in making a definitive diagnosis, and the importance in identifying a SMARCB1 deficiency as it will affect treatment options and may allow for enrollment in ongoing clinical trials.

SLC39A14 deficiency alters manganese homeostasis and excretion resulting in brain manganese accumulation and motor deficits in mice.

Solute carrier family 39, member 14 (SLC39A14) is a transmembrane transporter that can mediate the cellular uptake of zinc, iron, and manganese (Mn). Studies of Slc39a14 knockout (Slc39a14-/-) mice have documented that SLC39A14 is required for systemic growth, hepatic zinc uptake during inflammation, and iron loading of the liver in iron overload. The normal physiological roles of SLC39A14, however, remain incompletely characterized. Here, we report that Slc39a14-/- mice spontaneously display dramatic alterations in tissue Mn concentrations, suggesting that Mn is a main physiological substrate for SLC39A14. Specifically, Slc39a14-/- mice have abnormally low Mn levels in the liver coupled with markedly elevated Mn concentrations in blood and most other organs, especially the brain and bone. Radiotracer studies using 54Mn reveal that Slc39a14-/- mice have impaired Mn uptake by the liver and pancreas and reduced gastrointestinal Mn excretion. In the brain of Slc39a14-/- mice, Mn accumulated in the pons and basal ganglia, including the globus pallidus, a region susceptible to Mn-related neurotoxicity. Brain Mn accumulation in Slc39a14-/- mice was associated with locomotor impairments, as assessed by various behavioral tests. Although a low-Mn diet started at weaning was able to reverse brain Mn accumulation in Slc39a14-/- mice, it did not correct their motor deficits. We conclude that SLC39A14 is essential for efficient Mn uptake by the liver and pancreas, and its deficiency results in impaired Mn excretion and accumulation of the metal in other tissues. The inability of Mn depletion to correct the motor deficits in Slc39a14-/- mice suggests that the motor impairments represent lasting effects of early-life Mn exposure.

Esophagectomy for cancer in octogenarians: should we do it?

PURPOSE: Inconsistent data exists regarding esophagectomy outcomes in octogenarians undergoing transhiatal esophagectomy for esophageal cancer. METHODS: A retrospective review was performed for esophagectomy cancer patients between 2000 and 2012 at our tertiary referral center. Outcome data for octogenarians was compared to younger patients aged 20 to 79 years. A case-matched group of patients younger than 80 years old (n = 33) was included based on the Charlson comorbidity index with the octogenarian group (n = 33). Endpoints included operative morbidity and mortality as well as short- and long-term survival. RESULTS: Thirty-three octogenarians met inclusion criteria. The median age was 82 years, and 79% were male; 76% had adenocarcinoma, 87% had distal esophageal, and 52% had poorly differentiated tumors. Stages 0 through III were observed in 6, 18, 27, and 48% of octogenarians, respectively. Neoadjuvant therapy was administered to 70% of patients, with 48% experiencing downstaging. Transhiatal esophagectomy was performed in 82% of patients, with R0 resection in 94%. The mean hospital stay was 18 days, with morbidity and mortality rates 56 and 9%, respectively, not significantly different from 13-day hospital stay, 45% morbidity, and 9% mortality in younger patients. Cardiac, pulmonary, and surgical site complications occurred in 24, 27, and 6% of octogenarians, respectively. Anastomotic leak occurred in 18% and reoperations in 3%. The median, 3-year survival, and 5-year survival were 21 months, 55.9%, and 37.1%, respectively. Overall survival was worse for octogenarians (p < 0.001). CONCLUSIONS: Postoperative mortality, morbidity, and length of stay in octogenarians are comparable to younger patients, while the overall survival is worse. With appropriate patient selection, good outcomes can be accomplished in octogenarians undergoing esophagectomy for cancer.