Primary lymphoma of bone of the little finger: a case report and review of the literature.

Primary lymphoma of bone (PLB) is a rare, malignant lymphoid proliferation within bone accounting for less than 3% of all malignant bone tumors. In this case report, a 61-year-old female with past medical history of gout presented with pain and swelling in her right little finger. Initial radiographs demonstrated periostitis and soft tissue swelling about the right little finger. She returned three months later with progressive pain. Subsequent MRI and repeat radiographs demonstrated near complete destruction of the right little finger middle phalanx and periostitis with marrow infiltration at the right long finger. Given the rapid progression of disease, the differential diagnosis consisted primarily of aggressive neoplastic processes. The little finger ray was amputated through the level of the metacarpophalangeal joint and histopathology demonstrated large neoplastic cells that stained positive with CD45, CD20, and PAX5, compatible with diffuse large B-cell lymphoma. A subsequent normal bone marrow aspiration and PET-CT demonstrated no additional sites of disease, thus excluding secondary lymphoma to bone. To the best of our knowledge, this is the first case report of polyostotic PLB involving the hand. PLB of the hands may be initially misdiagnosed due to its rarity and clinical presentation mimicking rheumatological disease. Clinical vigilance in concert with close imaging follow-up is required to make the diagnosis in a timely fashion. We also review the existing PLB hand literature which consists of five cases.

Health change awareness and its association with weight loss following bariatric surgery.

OBJECTIVE: Patients' ability to judge health change over time has important clinical implications for treatment, but is understudied in longitudinal contexts with meaningful health change. We assess patients' awareness of health change for 5 years following bariatric surgery, and its association with weight loss. METHOD: Participants were part of the Longitudinal Assessment of Bariatric Surgery (N = 2,027). Perceived health change for each year was assessed by comparing it to self-reports of health on the SF-36 health survey. Participants were categorized as concordant when perceived and actual self-reported health change corresponded, and as discordant when they did not correspond. RESULTS: Year-to-year concordance between perceived and actual self-reported health change occurred less than 50% of the time. Discordance between perceived and actual health was associated with weight loss following surgery. Discordant-positive participants who perceived their health change as more positive than was warranted lost more weight post-surgery and thus had lower body mass index scores than concordant participants. Conversely, discordant-negative participants who perceived their health as worse than what was warranted lost less weight post-surgery and thus had higher body mass index scores. CONCLUSIONS: These results suggest that recollection of past health is generally poor and can be biased by salient factors during recall. Clinicians are advised to use caution when retrospective judgments of health are utilized. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Assessing the role of sow parity on PRRSv detection by RT-qPCR through weekly processing fluids monitoring in breeding herds.

The use of processing fluids to monitor the breeding herd's porcine reproductive and respiratory syndrome (PRRS) status has gained industry acceptance. However, little is known about PRRS virus RT-qPCR detection dynamics in processing fluids and factors that may contribute to maintain PRRS virus in the herd after an outbreak. This study aimed to describe weekly RT-qPCR processing fluid results in breeding herds after an outbreak and to evaluate the proportion of RT-qPCR positive results among parity groups. Processing tissues of 15 first parity (P1), 15 second parity (P2), and 15 third parity or higher (P3+) litters (parity groups) were collected weekly for between 19 and 46 weeks in nine breeding herds. Processing fluids were aggregated, and RT-qPCR tested by parity group weekly. Additionally, a subset of 743 processing fluid samples of litters that formed 50 parity groups, as previously described, were RT-qPCR tested individually at the litter level. The agreement between RT-qPCR results of processing fluid samples of parity groups (15 litters) and results based on individual litter testing was assessed using overall percent of agreement, Kappa statistic, and McNemar test. The association between RT-qPCR results and the parity group was evaluated using a generalized estimating equations model, after accounting for the effects of sampling week, breeding herd PRRS control strategy (i.e., open to replacements v/s closed) and herd. An autoregressive correlation structure was used to account for the repeated samplings within a herd in time. The overall agreement was 98 %, and Kappa statistic 0.955 (McNemar p = 1.0). Sensitivity of parity group processing fluid samples was estimated at 100 % (95 % CI 89-100 %), while specificity was estimated at 94 % (95 % CI 71-100 %). Although P1 aggregated litters had on average a higher proportion of RT-qPCR positive results from outbreak week 25 onwards, the proportion was not significantly different to the one observed for P2 and P3+ aggregated litters (p > 0.13). Additionally, herds that interrupted gilt entry had lower odds of PRRS RT-qPCR positivity than herds that continued entering gilts (OR = 0.35, 95 % CI 0.16-0.78). PRRS virus persistence in processing fluids was not affected by the sow parity effect in most of the breeding herds studied. No evidence of disagreement between RT-qPCR results of an aggregated sample of 15 litters and those of individual litters was observed. This level of litter aggregation testing strategy may be of particular use at the last stages of an elimination program under low PRRS virus prevalence.

Regional pediatric disaster network guides statewide telehealth initiation during COVID-19 pandemic.

BACKGROUND: Telehealth emerged early as an important tool to provide clinical care during the COVID-19 pandemic, but statewide implementation strategies were lacking. Needs assessment: We performed a needs assessment at 15 pediatrics clinics in Washington regarding their ability to institute telehealth. Fourteen clinics (93 percent response rate) responded; none had ability to perform telehealth visits. Clinics needed the following specific support structures: (1) an easily implementable, low-cost system, and (2) parity billing for telehealth services. Disaster effort: Two weeks after the needs assessment was performed, we facilitated direct telehealth initiation support to 45 Washington clinics and created a coalition of statewide advocacy groups. These groups advocated for (1) a statewide solution for non-network or poorly resourced providers, which was delivered by the WA Health Care Authority, and (2) parity billing, which was delivered by emergency governor action. CONCLUSION: Engagement with our regional pediatric disaster network was essential in providing guidance and expertise in this needs assessment, telehealth initiation process, and subsequent advocacy efforts. The power we have as pediatricians to coordinate with regional experts helped improve access to telehealth across Washington.

A Case of Tofacitinib-Induced Lymphomatoid Papulosis With Ocular Involvement.

ABSTRACT: Janus kinase (JAK) inhibitors are being prescribed with increasing regularity in dermatology. We report on a patient who initiated treatment with tofacitinib for refractory erythema elevatum diutinum and subsequently developed a novel cutaneous outbreak characterized by firm violaceous papules on the trunk and extremities along with conjunctival injection and periorbital inflammation. Biopsy of affected tissue from both the cutaneous and ophthalmologic sources demonstrated increased numbers of CD30+ large atypical cells amid a mixed inflammatory cell infiltrate, consistent with lymphomatoid papulosis. A review of the literature reveals a plausible mechanism for the induction of persistent JAK signaling in the presence of a JAK inhibitor. We discuss this mechanism in depth because it pertains to this patient and recommend continued vigilance with the use of these immunologic agents.

Fatty Acid Composition by Total Acyl Lipid Collision-Induced Dissociation Time-of-Flight (TAL-CID-TOF) Mass Spectrometry.

Total acyl lipid collision-induced dissociation time-of-flight (TAL-CID-TOF) mass spectrometry uses a quadrupole time-of-flight (QTOF) mass spectrometer to rapidly provide a comprehensive fatty acid composition of a biological lipid extract. Samples are infused into a QTOF instrument, operated in negative mode, and the quadrupole is used to transfer all, or a wide mass range of, precursor ions to the collision cell for fragmentation. Time-of-flight-acquired mass spectra provide mass accuracy and resolution sufficient for chemical formula determination of fatty acids in the complex mixture. Considering the limited number of reasonable CHO variants in fatty acids, one can discern acyl anions with the same nominal mass but different chemical formulas. An online application, LipidomeDB Data Calculation Environment, is employed to process the mass spectral output data and match identified fragments to target fragments at a resolution specified by the user. TAL-CID-TOF methodology is a useful discovery or screening tool to identify and compare fatty acid profiles of biological samples.

Engrafted Donor-Derived Clonal Hematopoiesis after Allogenic Hematopoietic Cell Transplantation is Associated with Chronic Graft-versus-Host Disease Requiring Immunosuppressive Therapy, but no Adverse Impact on Overall Survival or Relapse.

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-associated condition defined by the presence of a somatic mutation in a leukemia-associated gene in individuals who otherwise have no evidence of a hematologic malignancy. In the allogeneic hematopoietic cell transplantation (HCT) setting, clonal hematopoiesis (CH) mutations present in donor stem cells can be transferred to recipients at the time of HCT. Given that the consequences of donor-derived CH in HCT recipients are not entirely clear, we sought to investigate clinical outcomes in patients with engrafted donor-derived CH using a matched cohort analysis of both related and unrelated donors. Of 209 patients with next-generation sequencing performed before and after HCT, donor-derived CH mutations were detected in 15 (5.2%). DNMT3A was the most commonly mutated gene (9 of 15; 60%); mutations in SF3B1, CSF3R, STAT3, CBLB, TET2, and ASXL1 were also identified. Donor-derived CH was not associated with delayed neutrophil or platelet engraftment, and there was no impact on conversion to full donor chimerism. No patients with donor-derived CH experienced relapse, in contrast to 15.6% (7 of 45) in the matched control cohort without CH (P = .176). Donor-derived CH was not associated with worse overall survival; however, patients with donor-derived CH were more likely to develop chronic graft-versus-host disease (GVHD) necessitating systemic immunosuppressive therapy (IST) (P = .045) and less likely to discontinue IST (P = .03) compared with controls without donor-derived CH. We conclude that donor-derived CH does not have an adverse impact on relapse, survival, or engraftment outcomes but may potentiate a graft-versus-leukemia effect, as reflected by increased chronic GVHD necessitating IST.

Familial Alzheimer's disease mutations in amyloid protein precursor alter proteolysis by γ-secretase to increase amyloid ß-peptides of ≥45 residues.

Production of amyloid ß-protein (Aß) is carried out by the membrane-embedded γ-secretase complex. Mutations in the transmembrane domain of amyloid ß-protein precursor (APP) associated with early-onset familial Alzheimer's disease (FAD) can alter the ratio of aggregation-prone 42-residue Aß (Aß42) to 40-residue Aß (Aß40). However, APP substrate is proteolyzed processively by γ-secretase along two pathways: Aß49→Aß46→Aß43→Aß40 and Aß48→Aß45→Aß42→Aß38. Effects of FAD mutations on each proteolytic step are unknown, largely due to difficulties in detecting and quantifying longer Aß peptides. To address this, we carried out systematic and quantitative analyses of all tri- and tetrapeptide coproducts from proteolysis of wild-type and 14 FAD-mutant APP substrates by purified γ-secretase. These small peptides, including FAD-mutant forms, were detected by tandem mass spectrometry and quantified by establishing concentration curves for each of 32 standards. APP intracellular domain (AICD) coproducts were quantified by immunoblot, and the ratio of AICD products corresponding to Aß48 and Aß49 was determined by mass spectrometry. Levels of individual Aß peptides were determined by subtracting levels of peptide coproducts associated with degradation from those associated with production. This method was validated for Aß40 and Aß42 by specific ELISAs and production of equimolar levels of Aß and AICD. Not all mutant substrates led to increased Aß42/40. However, all 14 disease-causing mutations led to inefficient processing of longer forms of Aß ≥ 45 residues. In addition, the effects of certain mutations provided insight into the mechanism of processive proteolysis: intermediate Aß peptides apparently remain bound for subsequent trimming and are not released and reassociated.

Extraosseous multiple myeloma: imaging spectrum in the abdomen and pelvis.

Multiple myeloma represents a subset of plasma cell dyscrasias characterized by the proliferation of plasma cells typically in the bone marrow, representing approximately 1% of all cancers and 15% of hematologic malignancies. Often multiple myeloma is limited to the skeletal system; however, a small percentage (<5%) of patients will develop extraosseous manifestations. We review the current WHO classification of plasma cell dyscrasias and use multimodality imaging including US, CT, MRI, and PET-CT to illustrate the spectrum of extraosseous multiple myeloma in the abdomen and pelvis. Because extraosseous multiple myeloma is associated with a poorer prognosis and decreased survival, it is important for the radiologist to become familiar with a variety of extraosseous manifestations in the abdomen and pelvis, especially in a patient with a known diagnosis of multiple myeloma and the development of an abdominal or pelvic mass.

Metastatic renal clear cell carcinoma masquerading as a pyogenic granuloma on the lip.

Metastases to the face are rare. We report on a patient with a history of renal cell carcinoma who presented with a 1.2cm violaceous papule on his lower lip. Although clinically thought to be a pyogenic granuloma, biopsy revealed metastatic renal cell carcinoma recurring after 7 years of latency.

Survival of swine pathogens in compost formed from preprocessed carcasses.

An introduction of a Foreign Animal Disease (FAD) like African Swine Fever Virus (ASF) would be financially devastating. For example, ASF, a highly contagious pathogen with high mortality rates, is a World Health Organization reportable disease that has recently been spreading across Asia and Europe. Control of ASF would likely require mass euthanasia of infected and exposed animals similar to the United Kingdom's elimination of Foot and Mouth Disease (FMD). Subsequent disposal of infectious carcasses must adequately eliminate the virus and prevent further transmission of the disease. Although composting swine carcasses is widely used throughout the industry, limited data is available describing pathogen survival or elimination during this process. While current methods have evaluated the composting of swine carcasses under temperature-controlled settings, they have not considered the effects of adverse weather conditions (e.g., cold winter conditions) where composting is routinely performed. This study utilized preprocessing (grinding) of swine carcasses prior to composting, which decreases the amount of required carbon material and land space. The ability of composting to reduce the level of viral nucleic acid during cold weather conditions and the risk of environmental contamination that may occur during preprocessing was evaluated. In this study, pigs challenged with Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and Porcine Epidemic Diarrhea Virus (PEDV), common domestic diseases, before euthanasia provided infectious carcasses containing pathogen surrogates. Composting of preprocessed carcasses achieved adequate temperatures necessary to eliminate FAD and common swine pathogens during cold weather conditions (monitored by compost temperature over time, virus diagnostic testing, and swine bioassay for PRRSV and PEDV). Under the conditions of this study, composting preprocessed carcasses presents minimal risk to air and groundwater contamination. In conclusion, composting preprocessed euthanized swine under adverse weather conditions is a safe and feasible option for mass disposal of infected carcasses.

A workflow for visualizing human cancer biopsies using large-format electron microscopy.

Recent developments in large format electron microscopy have enabled generation of images that provide detailed ultrastructural information on normal and diseased cells and tissues. Analyses of these images increase our understanding of cellular organization and interactions and disease-related changes therein. In this manuscript, we describe a workflow for two-dimensional (2D) and three-dimensional (3D) imaging, including both optical and scanning electron microscopy (SEM) methods, that allow pathologists and cancer biology researchers to identify areas of interest from human cancer biopsies. The protocols and mounting strategies described in this workflow are compatible with 2D large format EM mapping, 3D focused ion beam-SEM and serial block face-SEM. The flexibility to use diverse imaging technologies available at most academic institutions makes this workflow useful and applicable for most life science samples. Volumetric analysis of the biopsies studied here revealed morphological, organizational and ultrastructural aspects of the tumor cells and surrounding environment that cannot be revealed by conventional 2D EM imaging. Our results indicate that although 2D EM is still an important tool in many areas of diagnostic pathology, 3D images of ultrastructural relationships between both normal and cancerous cells, in combination with their extracellular matrix, enables cancer researchers and pathologists to better understand the progression of the disease and identify potential therapeutic targets.

Pharmacokinetics and tissue concentrations of firocoxib in sows following oral administration.

The objectives of this study were to describe the pharmacokinetics of firocoxib following oral (PO) dosing and intravenous (IV) injection in sows. Seven healthy sows were administered 0.5 mg firocoxib/kg IV. Following a 23-d washout period, sows were administered firocoxib at 4.0 mg firocoxib/kg PO. Blood samples were collected at predetermined times for 72 hr after IV and 120 hr after PO administration. Plasma firocoxib concentration was measured using UPLC-MS/MS, and pharmacokinetic analysis was performed using noncompartmental procedures. Tissue firocoxib concentrations were determined at 5, 10 (n = 2/time point), and 21 d (n = 3) after PO administration. The geometric mean half-life following IV and PO administration was 16.6 and 22.5 hr, respectively. A mean peak plasma concentration (Cmax) of 0.06 µg/ml was recorded at 7.41 hr (Tmax ) after oral administration. Mean oral bioavailability was determined to be 70.3%. No signs of NSAID toxicity were observed on macroscopic and microscopic investigation. Firocoxib was detected in the skin with subcutaneous fat (0.02 µg/g) of one of three sows at 21 days postadministration. Additional work to establish appropriate meat withhold intervals in sows is required. Firocoxib was readily absorbed following PO administration. Further work is needed to better understand the analgesic effects for sows and piglets nursing sows administered firocoxib.

Primary Extranodal Nodular Lymphocyte Predominant Hodgkin Lymphoma Involving the Thyroid.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon lymphoma that accounts for 3-8% of all Hodgkin lymphomas. NLPHL typically presents as early stage disease with localized peripheral lymphadenopathy. Involvement of extranodal sites at the time of presentation occurs in 6% of cases and most commonly involves the spleen, liver, bone marrow, and Waldeyer ring. Primary extranodal NLPHL is exceedingly rare. We describe the first reported case involving the thyroid and review the six other previously described cases of primary extranodal NLPHL.

Two-dimensional Machiavellianism: Conceptualization, theory, and measurement of the views and tactics dimensions.

For over 45 years, research investigating Machiavellianism has largely used the same unidimensional approach, even though empirical research demonstrates that Machiavellianism is comprised of 2 robust dimensions: views and tactics. This article elaborates on the theory and conceptualization behind the 2 dimensions. It also documents the construction and validation of the 12-item Two-Dimensional Machiavellianism Scale (TDMS), which measures the cynical and untrusting views dimension, and the immoral interpersonal tactics dimension, across 6 samples (N = 3,886, 37.70% men) using confirmatory factor analysis (CFA) and item response theory. The 2-factor structure fitted the data well based on CFA, and was invariant across samples, gender, and over a 3-month period (N = 338, 36.39% men). Evidence of each subscale's construct validity was established using structural equation modeling. As expected, the Views subscale was primarily associated with misanthropy, hypersensitive narcissism, lower subjective well-being, and lower emotional stability. The Tactics subscale was primarily associated with psychopathy, lower conscientiousness, lower willingness to reciprocate, and "ends justified the means" behavior in ethical dilemmas. The TDMS enhances practical and conceptual understanding of Machiavellianism through demarcating the underlying motivations and addresses the need for an updated and psychometrically sound measure of Machiavellianism. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Designed Helical Peptides as Functional Probes for γ-Secretase.

γ-Secretase is a membrane-embedded aspartyl protease complex with presenilin as the catalytic component that cleaves within the transmembrane domain (TMD) of >90 known substrates, including the amyloid precursor protein (APP) of Alzheimer's disease. Processing by γ-secretase of the APP TMD produces the amyloid ß-peptide (Aß), including the 42-residue variant (Aß42) that pathologically deposits in the Alzheimer brain. Complex proteolysis of APP substrate by γ-secretase involves initial endoproteolysis and subsequent carboxypeptidase trimming, resulting in two pathways of Aß production: Aß49 → Aß46 → Aß43 → Aß40 and Aß48 → Aß45 → Aß42 → Aß38. Dominant mutations in APP and presenilin cause early onset familial Alzheimer's disease (FAD). Understanding how γ-secretase processing of APP is altered in FAD is essential for elucidating pathogenic mechanisms in FAD and developing effective therapeutics. To improve our understanding, we designed synthetic APP-based TMD substrates as convenient functional probes for γ-secretase. Installation of the helix-inducing residue α-aminoisobutyric acid provided full TMD helical substrates while also facilitating their synthesis and increasing the solubility of these highly hydrophobic peptides. Through mass spectrometric analysis of proteolytic products, synthetic substrates were identified that were processed in a manner that reproduced physiological processing of APP substrates. Validation of these substrates was accomplished through mutational variants, including the installation of two natural APP FAD mutations. These FAD mutations also resulted in increased levels of formation of Aß-like peptides corresponding to Aß45 and longer, raising the question of whether the levels of such long Aß peptides are indeed increased and might contribute to FAD pathogenesis.

PCV3-associated disease in the United States swine herd.

Porcine circovirus-associated disease encompasses multiple disease syndromes including porcine circovirus 2 systemic diseases, reproductive failure, and porcine dermatitis and nephropathy syndrome. Until recently, porcine circovirus 2 was the only species associated with the porcine circovirus-associated disease. In this report, diagnostic investigations of thirty-six field cases submitted from multiple production systems, numerous sites and varied geographic locations demonstrated porcine circovirus 3 within lesions by in situ hybridization including fetuses with myocarditis, weak-born neonatal piglets with encephalitis and myocarditis, from cases of porcine dermatitis and nephropathy syndrome, and in weaned pigs with systemic periarteritis. Porcine circovirus 3 was detected by PCR in numerous fetuses and perinatal piglets at high viral loads (trillions of genome copies per mL of tissue homogenate). Samples from all cases in this study were assayed and found negative for porcine circovirus 2 by PCR. Metagenomic sequencing was performed on a subset of reproductive cases, consisting of sixteen fetuses/fetal sample pools. PCV3 was identified in all pools and the only virus identified in fourteen pools. Based on these data, porcine circovirus 3 is considered a putative cause of reproductive failure, encephalitis and myocarditis in perinatal piglets, porcine dermatitis and nephropathy syndrome, and periarteritis in swine in the United States.

An unmet clinical need: The history of thrombus imaging.

Robust thrombus imaging is an unresolved clinical unmet need dating back to the mid 1970s. While early molecular imaging approaches began with nuclear SPECT imaging, contrast agents for virtually all biomedical imaging modalities have been demonstrated in vivo with unique strengths and common weaknesses. Two primary molecular imaging targets have been pursued for thrombus imaging: platelets and fibrin. Some common issues noted over 40 years ago persist today. Acute thrombus is readily imaged with all probes and modalities, but aged thrombus remains a challenge. Similarly, anti-coagulation continues to interfere with and often negate thrombus imaging efficacy, but heparin is clinically required in patients suspected of pulmonary embolism, deep venous thrombosis or coronary ruptured plaque prior to confirmatory diagnostic studies have been executed and interpreted. These fundamental issues can be overcome, but an innovative departure from the prior approaches will be needed.