Utica/Point Pleasant brine isotopic compositions (δ7Li, δ11B, δ138Ba) elucidate mechanisms of lithium enrichment in the Appalachian Basin.

Global Li production will require a ∼500 % increase to meet 2050 projected energy storage demands. One potential source is oil and gas wastewater (i.e., produced water or brine), which naturally has high total dissolved solids (TDS) concentrations, that can also be enriched in Li (>100 mg/L). Understanding the sources and mechanisms responsible for high naturally-occurring Li concentrations can aid in efficient targeting of these brines. The isotopic composition (δ7Li, δ11B, δ138Ba) of produced water and core samples from the Utica Shale and Point Pleasant Formation (UPP) in the Appalachian Basin, USA indicates that depth-dependent thermal maturity and water-rock interaction, including diagenetic clay mineral transformations, likely control Li concentrations. A survey of Li content in produced waters throughout the USA indicates that Appalachian Basin brines from the Marcellus Shale to the UPP have the potential for economic resource recovery.

Transthyretin Cardiac Amyloidosis Disguised as Light Chain Amyloidosis or Multiple Myeloma?

We describe 2 challenging cases of cardiac transthyretin amyloidosis initially treated as cardiac amyloidosis light chain in the setting of active myeloma. Endomyocardial biopsy with mass spectrometry was essential to confirm the appropriate diagnosis to direct the treatment.

Recurrent Cardiac Sarcoidosis and Giant Cell Myocarditis After Heart Transplant: A Case Report and Systematic Literature Review.

Recurrence of cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) after heart transplant is rare, with rates of 5% in CS and 8% in GCM. We aim to identify all reported cases of recurrence in the literature and to assess clinical course, treatments, and outcomes to improve understanding of the conditions. A systematic review, utilizing Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, was conducted by searching MEDLINE/PubMed and Embase of all available literature describing post-transplant recurrent granulomatous myocarditis, CS, or GCM. Data on demographics, transplant, recurrence, management, and outcomes data were collected from each publication. Comparison between the 2 groups were made using standard statistical approaches. Post-transplant GM recurrence was identified in 39 patients in 33 total publications. Reported cases included 24 GCM, 12 CS, and 3 suspected cases. Case reports were the most frequent form of publication. Mean age of patients experiencing recurrence was 42 years for GCM and 48 years for CS and favored males (62%). Time to recurrence ranged from 2 weeks to 9 years post-transplant, occurring earlier in GCM (mean 1.8 vs 3.0 years). Endomyocardial biopsies (89%) were the most utilized diagnostic method over cardiac magnetic resonance and positron emission tomography. Recurrence treatment regimens involved only steroids in 40% of CS, whereas other immunomodulatory regimens were utilized in 70% of GCM. In conclusion, GCM and CS recurrence after cardiac transplantation holds associated risks including concurrent acute cellular rejection, a higher therapeutic demand for GCM recurrence compared with CS, and mortality. New noninvasive screening techniques may help modify post-transplant monitoring regimens to increase both early detection and treatment of recurrence.

Pathologic Criteria for the Diagnosis of Usual Interstitial Pneumonia vs Fibrotic Hypersensitivity Pneumonitis in Transbronchial Cryobiopsies.

Transbronchial cryobiopsy (TBCB) is increasingly used for the diagnosis of fibrosing interstitial pneumonias, but there are few detailed descriptions of the pathologic findings in such cases. It has been proposed that a combination of patchy fibrosis and fibroblast foci with an absence of alternative features is diagnostic of usual interstitial pneumonia (UIP; ie, idiopathic pulmonary fibrosis [IPF]) in TBCB. In this study, we reviewed 121 TBCB in which a diagnosis of fibrotic hypersensitivity pneumonitis (FHP; n = 83) or IPF (n = 38) was made by multidisciplinary discussion and evaluated a range of pathologic features. Patchy fibrosis was found in 65 of 83 (78%) biopsies from FHP and 32of 38 (84%) biopsies from UIP/IPF cases. Fibroblast foci were present in 47 of 83 (57%) FHP and 27 of 38 (71%) UIP/IPF cases. Fibroblast foci/patchy fibrosis combined did not favor either diagnosis. Architectural distortion was seen in 54 of 83 (65%) FHP and 32 of 38 (84%) UIP/IPF cases (odds ratio [OR] for FHP, 0.35; P = .036) and honeycombing in 18 of 83 (22%) and 17 of 38 (45%), respectively (OR, 0.37; P = .014). Airspace giant cells/granulomas were present in 13 of 83 (20%) FHP and 1 of 38 (2.6%) UIP/IPF cases (OR for FHP, 6.87; P = .068), and interstitial giant cells/granulomas in 20 of 83 (24%) FHP and 0 of 38 (0%) UIP/IPF (OR, 6.7 x 106; P = .000). We conclude that patchy fibrosis plus fibroblast foci can be found in TBCB from both FHP and UIP/IPF. The complete absence of architectural distortion/honeycombing favors a diagnosis of FHP, as does the presence of airspace or interstitial giant cells/granulomas, but these measures are insensitive, and many cases of FHP cannot be separated from UIP/IPF on TBCB.

Paleolakes and socioecological implications of last glacial "greening" of the South African interior.

Determining the timing and drivers of Pleistocene hydrological change in the interior of South Africa is critical for testing hypotheses regarding the presence, dynamics, and resilience of human populations. Combining geological data and physically based distributed hydrological modeling, we demonstrate the presence of large paleolakes in South Africa's central interior during the last glacial period, and infer a regional-scale invigoration of hydrological networks, particularly during marine isotope stages 3 and 2, most notably 55 to 39 ka and 34 to 31 ka. The resulting hydrological reconstructions further permit investigation of regional floral and fauna responses using a modern analog approach. These suggest that the climate change required to sustain these water bodies would have replaced xeric shrubland with more productive, eutrophic grassland or higher grass-cover vegetation, capable of supporting a substantial increase in ungulate diversity and biomass. The existence of such resource-rich landscapes for protracted phases within the last glacial period likely exerted a recurrent draw on human societies, evidenced by extensive pan-side artifact assemblages. Thus, rather than representing a perennially uninhabited hinterland, the central interior's underrepresentation in late Pleistocene archeological narratives likely reflects taphonomic biases stemming from a dearth of rockshelters and regional geomorphic controls. These findings suggest that South Africa's central interior experienced greater climatic, ecological, and cultural dynamism than previously appreciated and potential to host human populations whose archaeological signatures deserve systematic investigation.

Goiter and Abdominal Mass: A Rare Presentation of Riedel's Thyroiditis.

Riedel's thyroiditis (RT) is a rare inflammatory autoimmune disease, often associated with various forms of systemic fibrosis such as sclerosing mesenteritis (SM). A woman in her late 30s presented with a diffusely enlarged firm goiter and a mesenteric mass complicated by biliary obstruction and hydronephrosis. Labs and thyroid ultrasound were consistent with autoimmune thyroiditis. Abdominal imaging demonstrated a mesenteric mass that encased mesenteric vessels and ureter. Flow cytometry and infectious workup were negative. Both thyroid and mesenteric biopsies revealed dense fibrosis with patchy lymphoplasmacytic aggregates, no evidence of carcinoma, lymphoma, or IgG4-related disease, which confirmed diagnoses of RT and SM. She improved clinically with steroids. The coincidental timing of thyroid enlargement and the mesenteric mass, and the similarity in histology suggest an association between RT and SM. Overall, the case highlights the challenges in diagnosing RT given its rarity and emphasises the importance of early treatment to prevent systemic involvement.

Subacromial-Subdeltoid Bursitis With Rice Bodies After Rotator Cuff Repair With a Collagen Scaffold Implant: A Case Report.

CASE: We report the second-known case of subacromial-subdeltoid bursitis with rice bodies after rotator cuff repair with a Smith + Nephew REGENETEN bovine-derived bioinductive collagen scaffold implant. After the removal of rice bodies and a portion of implant that had not incorporated, the patient recovered well and made a full return to work and recreational activities. CONCLUSION: This case demonstrates that persistent pain, swelling, or decreased range of motion for several months after rotator cuff repair with the use of a collagen implant may warrant a relatively early magnetic resonance imaging to evaluate for underlying pathology. It also provides a framework for physicians who may see similar patients in the future.

Leiomyosarcoma of the Nasal Cavity and Paranasal Sinuses: A Case Report and Comprehensive Review of the Literature.

Sinonasal leiomyosarcoma (LMS) is a rare and aggressive mesenchymal tumor with smooth muscle differentiation. The sinonasal tract is an unusual primary site for LMS, as scant smooth muscle exists in this location, with only 75 cases reported in the English literature including the case presented herein. Sinonasal LMS is considered an aggressive head and neck tumor with significant potential for recurrence and metastasis. Since recurrence is high and the potential for late metastasis exists, lifelong follow-up in these patients would be beneficial, especially among those with previous history of RB.

Palmar and plantar fibromatosis: a review.

Palmar fibromatosis (Dupuytren disease/contracture) is the most common type of fibromatosis, defined as a benign proliferation of fibroblasts and myofibroblasts. The disease process is most common in white, middle-aged and older men occurring at the distal palmar crease leading to nodules and contracture, which in many cases recur after surgical treatment. In a similar process, plantar fibromatosis (Ledderhose disease) is a proliferation of fibroblasts and myofibroblasts on the plantar aponeurosis of mostly middle-aged patients that may lead to painful nodules but usually does not lead to contracture. Both processes are histologically similar, composed of a bland cellular proliferation of spindle cells with a bluish appearance and with a variable amount of background collagen, depending on the age of the lesion. The etiology of both lesions is still uncertain, while treatment ranges from observation to surgery, with some pharmacologic agents being investigated with mixed success. In this paper we provide an overview of both processes with regards to clinical and radiologic findings, pathophysiology, diagnosis, treatment, and prognosis.

Cardiac sarcoidosis in the donor heart without extracardiac manifestations.

A middle-aged woman who received heart transplantation for end-stage sarcoid cardiomyopathy developed recurrent cardiac sarcoidosis in the donor heart. She presented 5 years post-transplantation with heart block and systolic dysfunction, without extracardiac involvement. Her disease was unresponsive to corticosteroids. Routine functional imaging may help identify such recurrences.

Primary cardiac low-grade neuroendocrine tumor: a case report and review of the literature.

Primary tumors of the heart are uncommon; even rarer are primary cardiac neuroendocrine tumors. To our knowledge, only two cases have been described to date, both being high-grade tumors. We report a solitary low-grade neuroendocrine tumor of the heart, unexpectedly discovered during aortic valve repair for infectious bacterial endocarditis on the wall of the right ventricle in a 44-year-old man with a history of balloon valvulotomy as a child. Frozen section was sent intraoperatively and demonstrated a plasmacytoid neoplasm. Final pathology of the biopsies showed a tumor composed of both cohesive and discohesive plasmacytoid cells separated by a vascular network and strands of fibrosis. The tumor showed strong reactivity for AE1/3, synaptophysin, and CDX2 with focal reactivity for chromogranin-A and CD56. Neither necrosis nor a mitotic rate of greater than 2 mitoses per 2 mm2 was seen. A colonoscopy was performed and demonstrated only a tubular adenoma. An esophagogastroduodenoscopy was unremarkable. PET-CT DOTATATE, performed after complete resection of the tumor, demonstrated no abnormal radiotracer uptake. The patient continues to do well at present, 1 year later, and reports no symptoms attributable to carcinoid syndrome or disease progression. The patient was assigned by medical oncology to yearly follow-up and imaging, and is considered to have no evidence of disease.

Metabolic studies of selective androgen receptor modulators RAD140 and S-23 in horses.

This paper describes the studies of the in vitro biotransformation of two selective androgen receptor modulators (SARMs), namely, RAD140 and S-23, and the in vivo metabolism of RAD140 in horses using ultra-high performance liquid chromatography-high resolution mass spectrometry. in vitro metabolic studies of RAD140 and S-23 were performed using homogenised horse liver. The more prominent in vitro biotransformation pathways for RAD140 included hydrolysis, hydroxylation, glucuronidation and sulfation. Metabolic pathways for S-23 were similar to those for other arylpropionamide-based SARMs. The administration study of RAD140 was carried out using three retired thoroughbred geldings. RAD140 and the majority of the identified in vitro metabolites were detected in post-administration urine samples. For controlling the misuse of RAD140 in horses, RAD140 and its metabolite in sulfate form gave the longest detection time in hydrolysed urine and could be detected for up to 6 days post-administration. In plasma, RAD140 itself gave the longest detection time of up to 13 days. Apart from RAD140 glucuronide, the metabolites of RAD140 described herein have never been reported before.

Tiludronic acid can be detected in blood and urine samples from Thoroughbred racehorses over 3 years after last administration.

BACKGROUND: Administration of bisphosphonates, including tiludronic acid, to Thoroughbred racehorses below 3 and a half years of age is prohibited in most racing jurisdictions. OBJECTIVES: To determine if evidence of administration of tiludronic acid could be obtained from analysis of blood and urine samples beyond 40 days after administration. STUDY DESIGN: Retrospective cohort. METHODS: Horses maintained in a highly controlled environment and treated with Tildren®a were selected from clinical records. Twenty-four horses were identified, 21 of which were still in race training. Blood and urine samples were collected and analysed for the presence of tiludronic acid using ultra-high-performance liquid chromatography-high-resolution mass spectrometry. RESULTS: Tiludronic acid was detected in samples from every horse, including two that had been given a therapeutic dose of the drug 3 years prior to sample collection. The estimated concentrations of tiludronic acid in the blood collected at least 2 years post-administration were consistently very low (less than 0.3 ng/mL). The estimated concentrations in urine were less consistent and were generally lower than those in blood, although higher levels were inconsistently detected in individual horses (up to about 16 ng/mL almost 1 year post-administration in 1 horse and about 3.7 ng/mL at almost 3 years post-administration in another). MAIN LIMITATIONS: The study was performed in horses that are older than the primary target group. A single sample was obtained from most horses and so we cannot comment on elimination profiles. CONCLUSIONS: Evidence that a therapeutic dose of tiludronic acid has been administered to a horse can be obtained from detection of the drug in blood and urine samples over 3 years after it was administered.

Emergency ventilator for COVID-19.

The COVID-19 pandemic disrupted the world in 2020 by spreading at unprecedented rates and causing tens of thousands of fatalities within a few months. The number of deaths dramatically increased in regions where the number of patients in need of hospital care exceeded the availability of care. Many COVID-19 patients experience Acute Respiratory Distress Syndrome (ARDS), a condition that can be treated with mechanical ventilation. In response to the need for mechanical ventilators, designed and tested an emergency ventilator (EV) that can control a patient's peak inspiratory pressure (PIP) and breathing rate, while keeping a positive end expiratory pressure (PEEP). This article describes the rapid design, prototyping, and testing of the EV. The development process was enabled by rapid design iterations using additive manufacturing (AM). In the initial design phase, iterations between design, AM, and testing enabled a working prototype within one week. The designs of the 16 different components of the ventilator were locked by additively manufacturing and testing a total of 283 parts having parametrically varied dimensions. In the second stage, AM was used to produce 75 functional prototypes to support engineering evaluation and animal testing. The devices were tested over more than two million cycles. We also developed an electronic monitoring system and with automatic alarm to provide for safe operation, along with training materials and user guides. The final designs are available online under a free license. The designs have been transferred to more than 70 organizations in 15 countries. This project demonstrates the potential for ultra-fast product design, engineering, and testing of medical devices needed for COVID-19 emergency response.

Rotational Energy Transfer in Highly Excited States of Lithium Dimer: Experiment and Modeling.

We report level-resolved rate coefficients for collision-induced rotational energy transfer in the 7Li2*-Ne system, with 7Li2* in the highly electronically excited E(3)1Σg+(vi = 4, ji = 31) and F(4)1Σg+(vi = 10, ji = 31) states. The distributions of rate coefficients are strikingly different from those previously measured for the A(1)1Σu+(vi = 2-24, ji = 30) state of the same molecule, falling off much more rapidly with increasing rotational quantum number change |Δj|. The reason for the difference was explored by means of an inverse Monte Carlo approach employing classical trajectories and a model potential, which was adjusted to give agreement with experiment. The modeling strongly suggests that the E and F state interaction potentials are much more nearly isotropic than that of the A state. The resulting dramatic reduction in rate coefficient, especially for large |Δj|, may be relevant in the relaxation of gases at high temperatures.

Benign lesions of the mediastinum: A review with emphasis on cytology and small biopsy specimens.

This review focuses on the diagnosis of select benign processes, ranging from reactive entities to heterotopic tissues to neoplasms, which may occur in the mediastinum. Currently, the mediastinum can be evaluated and biopsied with endoscopic procedures. Therefore, cytopathology specimens, fine needle aspirations, and small biopsies play an important role in the diagnosis of these lesions. In this review, an emphasis is given to relevant clinical presentations, histologic and cytologic findings, differential diagnoses, ancillary testing, and interpretation. Pitfalls are reviewed and discussed in each section. It is important for both surgical pathologists and cytopathologists to be familiar with these entities and their cytologic and histologic features that may be helpful in reaching a diagnosis.

Barium Isotopes Track the Source of Dissolved Solids in Produced Water from the Unconventional Marcellus Shale Gas Play.

Waters coproduced with hydrocarbons from unconventional oil and gas reservoirs such as the hydraulically fractured Middle Devonian Marcellus Shale in the Appalachian Basin, USA, contain high levels of total dissolved solids (TDS), including Ba, which has been variously ascribed to drilling mud dissolution, interaction with pore fluids or shale exchangeable sites, or fluid migration through fractures. Here, we show that Marcellus Shale produced waters contain some of the heaviest Ba (high 138Ba/134Ba) measured to date (δ138Ba = +0.36‰ to +1.49‰ ± 0.06‰) and are distinct from overlying Upper Devonian/Lower Mississippian reservoirs (δ138Ba = -0.83‰ to -0.52‰). Marcellus Shale produced water values do not overlap with drilling mud barite (δ138Ba ≈ 0.0‰) and are significantly offset from Ba reservoirs within the producing portion of the Marcellus Shale, including exchangeable sites and carbonate cement. Precipitation, desorption, and diffusion processes are insufficient or in the wrong direction to produce the observed enrichments in heavy Ba. We hypothesize that the produced water is derived primarily from brines adjacent to and most likely below the Marcellus Shale, although such deep brines have not yet been obtained for Ba isotope analysis. Barium isotopes show promise for tracking formation waters and for understanding water-rock interaction under downhole conditions.

Ostrich eggshell bead strontium isotopes reveal persistent macroscale social networking across late Quaternary southern Africa.

Hunter-gatherer exchange networks dampen subsistence and reproductive risks by building relationships of mutual support outside local groups that are underwritten by symbolic gift exchange. Hxaro, the system of delayed reciprocity between Ju/'hoãn individuals in southern Africa's Kalahari Desert, is the best-known such example and the basis for most analogies and models of hunter-gatherer exchange in prehistory. However, its antiquity, drivers, and development remain unclear, as they do for long-distance exchanges among African foragers more broadly. Here we show through strontium isotope analyses of ostrich eggshell beads from highland Lesotho, and associated strontium isoscape development, that such practices stretch back into the late Middle Stone Age. We argue that these exchange items originated beyond the macroband from groups occupying the more water-stressed subcontinental interior. Tracking the emergence and persistence of macroscale, transbiome social networks helps illuminate the evolution of social strategies needed to thrive in stochastic environments, strategies that in our case study show persistence over more than 33,000 y.

Educational Case: Identification of Pulmonary Mycobacteria.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

SMARCA4-Deficient Thoracic Sarcoma: A Case Report and Review of Literature.

SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS) is a recently described entity with a poor prognosis that is defined by certain genetic alterations in the BAF chromatin remodeling complex, specifically SMARCA4 and SMARCA2. We present a case of a SMARCA4-DTS in a 59 year-old male with a heavy smoking history who was found to have an unexpected right upper lobe lung mass on routine chest radiograph after a visit to his primary care physician. This led to a biopsy with a diagnosis of poorly differentiated carcinoma at an outside institution. The patient was subsequently seen at our facility for surgical intervention. The right upper lobectomy contained a 7.2-cm poorly differentiated malignancy with slightly discohesive cells arranged in sheets and nests, abundant geographic necrosis, and with many areas showing rhabdoid morphology. The tumor was focally reactive for CK7, AE1/3, Cam5.2, and SALL4 and showed scattered reactivity for CD34 and SOX2. There was complete loss of reactivity for both SMARCA4 and SMARCA2. The histology and immunophenotype were all consistent with the diagnosis of a SMARCA4-DTS. Next-generation sequencing showed a frameshift mutation in the SMARCA4 gene and no abnormality with the SMARCA2 gene. Interestingly, this tumor was confined to the pulmonary parenchyma with no invasion of the visceral pleura nor the mediastinum and with no clinically apparent metastases at the time of presentation. This case is presented to add to the cohort of cases described to date and to discuss the immunohistochemical and molecular findings with regard to SMARCA2.