Melanocytic Matricoma: A Potential Mimic of Malignant Melanoma.

Melanocytic matricoma is a rare dermal tumor that typically presents on the sun-damaged skin of older patients. While there is controversy in the literature regarding the proper characterization of this tumor, there are certain histological and immunohistochemical features that have been described. This report presents a case of melanocytic matricoma with several unusual features that were initially feared to be malignant melanoma. Careful histologic and immunohistochemical analysis was required to rule out malignant melanoma and make the correct diagnosis. Given the rarity of melanocytic matricoma and the potential for it to mimic malignant melanoma, it is important for pathologists to keep melanocytic matricoma on the differential and be aware of the clinical, histological, and immunohistochemical features of this tumor.

Impact of the COVID-19 pandemic on hepatitis C outcomes at a health-system specialty pharmacy.

BACKGROUND: The goal of hepatitis C virus (HCV) treatment is to cure the patient of the infection, defined as a nondetectable HCV RNA at least 12 weeks after treatment completion, or sustained virologic response (SVR). The COVID-19 pandemic has presented new barriers to care in the treatment of patients with HCV that resulted in a transition to tele-health services at many health systems to overcome these barriers. OBJECTIVE: To assess the real-world impact of the COVID-19 pandemic and the subsequent shift to a telehealth model on collection of SVR data and other HCV treatment outcomes in a health-system setting. METHODS: Subjects who received a referral for an HCV direct-acting antiviral agent between January 1, 2018, and November 30, 2020, and were aged 18 years or older at time of enrollment were placed in either "pre-COVID-19" or "COVID-19" cohorts based on enrollment date. The primary endpoint of this study evaluated confirmed SVR to treatment determined by the absence of HCV RNA by polymerase chain reaction testing at least 12 weeks after completion of drug therapy. Secondary endpoints evaluated completion of medication therapy and adherence to laboratory appointments. RESULTS: 1,504 patients met study inclusion criteria (pre-COVID-19 cohort, n = 1,230; COVID-19 cohort, n = 274). The COVID-19 cohort demonstrated significantly lower therapy completion rates (P = 0.001), were less likely to obtain SVR laboratory tests (P < 0.001), and had a significantly lower confirmed SVR rate (P < 0.001) compared with the pre-COVID-19 cohort. In a subset of patients who completed therapy and had SVR laboratory tests collected, there were no significant differences observed in the rate of patients who achieved SVR (P = 0.959). CONCLUSIONS: During the COVID-19 pandemic, patients with HCV were significantly less likely to complete therapy or participate in SVR laboratory work. Further studies are needed to determine if offering a telehealth option for our patients in a post-COVID-19 environment would offer any additional advantage in increasing access to care for patients with HCV. DISCLOSURES: No outside funding supported this study. Dr Cooper is an employee of the University of Kentucky whose position was partially funded by Gilead Sciences, Inc.

Association of chronic pain with comorbidities and health care utilization: a retrospective cohort study using health administrative data.

ABSTRACT: Health administrative data provide a potentially robust information source regarding the substantial burden chronic pain exerts on individuals and the health care system. This study aimed to use health administrative data to estimate comorbidity prevalence and annual health care utilization associated with chronic pain in Newfoundland and Labrador, Canada. Applying the validated Chronic Pain Algorithm to provincial Fee-for-Service Physician Claims File data (1999-2009) established the Chronic Pain (n = 184,580) and No Chronic Pain (n = 320,113) comparator groups. Applying the Canadian Chronic Disease Surveillance System coding algorithms to Claims File and Provincial Discharge Abstract Data (1999-2009) determined the prevalence of 16 comorbidities. The 2009/2010 risk and person-year rate of physician and diagnostic imaging visits and hospital admissions were calculated and adjusted using the robust Poisson model with log link function (risks) and negative binomial model (rates). Results indicated a significantly higher prevalence of all comorbidities and up to 4 times the odds of multimorbidity in the Chronic Pain Group (P-value < 0.001). Chronic Pain Group members accounted for 58.8% of all physician visits, 57.6% of all diagnostic imaging visits, and 54.2% of all hospital admissions in 2009/2010, but only 12% to 16% of these were for pain-related conditions as per recorded diagnostic codes. The Chronic Pain Group had significantly higher rates of physician visits and high-cost hospital admission/diagnostic imaging visits (P-value < 0.001) when adjusted for demographics and comorbidities. Observations made using this methodology supported that people identified as having chronic pain have higher prevalence of comorbidities and use significantly more publicly funded health services.

Identifying cases of chronic pain using health administrative data: A validation study.

BACKGROUND: Most prevalence estimates of chronic pain are derived from surveys and vary widely, both globally (2%-54%) and in Canada (6.5%-44%). Health administrative data are increasingly used for chronic disease surveillance, but their validity as a source to ascertain chronic pain cases is understudied. AIM: The aim of this study was to derive and validate an algorithm to identify cases of chronic pain as a single chronic disease using provincial health administrative data. METHODS: A reference standard was developed and applied to the electronic medical records data of a Newfoundland and Labrador general population sample participating in the Canadian Primary Care Sentinel Surveillance Network. Chronic pain algorithms were created from the administrative data of patient populations with chronic pain, and their classification performance was compared to that of the reference standard via statistical tests of selection accuracy. RESULTS: The most performant algorithm for chronic pain case ascertainment from the Medical Care Plan Fee-for-Service Physicians Claims File was one anesthesiology encounter ever recording a chronic pain clinic procedure code OR five physician encounter dates recording any pain-related diagnostic code in 5 years with more than 183 days separating at least two encounters. The algorithm demonstrated 0.703 (95% confidence interval [CI], 0.685-0.722) sensitivity, 0.668 (95% CI, 0.657-0.678) specificity, and 0.408 (95% CI, 0.393-0.423) positive predictive value. The chronic pain algorithm selected 37.6% of a Newfoundland and Labrador provincial cohort. CONCLUSIONS: A health administrative data algorithm was derived and validated to identify chronic pain cases and estimate disease burden in residents attending fee-for-service physician encounters in Newfoundland and Labrador.

Contexte: La plupart des estimations de prévalence de la douleur chronique sont tirées d'enquêtes et varient considérablement, à la fois dans le monde (2 % -54 %) et au Canada (6,5 % - 44 %). Les données administratives sur la santé utilisées pour la surveillance des maladies chroniques, mais leur validité comme source pour déterminer les cas de douleur chronique est sous-étudiée.Objectif: Le but de cette étude était de dériver et de valider un algorithme pour répertorier les cas de douleur chronique comme une seule maladie chronique en utilisant les données administratives provinciales sur la santé.Méthodes: Une norme de référence a été élaborée et appliquée aux données des dossiers médicaux électroniques d'un échantillon de la population générale de Terre-Neuve-et-Labrador participant au Réseau canadien de surveillance sentinelle en soins primaires. Des algorithmes de douleur chronique ont été créés à partir des données administratives de populations de patients souffrant de douleur chronique et leur rendement en matière de classification a été comparé à celui de la norme de référence par le biais de tests statistiques sur la précision de sélection.Résultats: L'algorithme le plus performant pour la détermination des cas de douleur chronique à partir du Registre des paiements des soins médicaux rémunérés à l'acte était une seule consultation en anesthésiologie au cours de laquelle un code de procédure d'intervention clinique en matière de douleur chronique était enregistré OU cinq consultations médicales en cinq ans au cours desquelles était enregistré tout code de diagnostic lié à la douleur, avec une période de plus de 183 jours entre au moins deux consultations.L'algorithme a démontré une sensibilité de 0,703 (intervalle de confiance [IC] à 95 %, 0,685 à 0,722), une spécificité de 0,668 (IC 95 %, 0,657-0,678) et une valeur prédictive positive de 0,408 (IC 95 %, 0,393-0,423). L'algorithme de la douleur chronique a sélectionné 37,6 % d'une cohorte provinciale de Terre-Neuve-et-Labrador.Conclusions: Un algorithme de données administratives sur la santé a été dérivé et validé pour répertorier les cas de douleur et estimer le fardeau de la maladie chez les résidents ayant consulté un médecin rémunéré à l'acte à Terre-Neuve et Labrador.

Diving behaviour of Cuvier's beaked whales (Ziphius cavirostris) off Cape Hatteras, North Carolina.

Cuvier's beaked whales exhibit exceptionally long and deep foraging dives. The species is little studied due to their deep-water, offshore distribution and limited time spent at the surface. We used LIMPET satellite tags to study the diving behaviour of Cuvier's beaked whales off Cape Hatteras, North Carolina from 2014 to 2016. We deployed 11 tags, recording 3242 h of behaviour data, encompassing 5926 dives. Dive types were highly bimodal; deep dives (greater than 800 m, n = 1408) had a median depth of 1456 m and median duration of 58.9 min; shallow dives (50-800 m, n = 4518) were to median depths of 280 m with a median duration of 18.7 min. Most surface intervals were very short (median 2.2 min), but all animals occasionally performed extended surface intervals. We found no diel differences in dive depth or the percentage of time spent deep diving, but whales spent significantly more time near the surface at night. Other populations of this species exhibit similar dive patterns, but with regional differences in depth, duration and inter-dive intervals. Satellite-linked tags allow for the collection of long periods of dive records, including the occurrence of anomalous behaviours, bringing new insights into the lives of these deep divers.

Executive control during episodic retrieval: multiple prefrontal processes subserve source memory.

During recognition, one may sense items as familiar (item memory) and additionally recollect specific contextual details of the earlier encounters (source memory). Cognitive theory suggests that, unlike item memory, source memory requires controlled cue specification and monitoring processes. Functional imaging suggests that such processes may depend on left prefrontal cortex (PFC). However, the nature and possible anatomical segregation of these processes remains unknown. Using functional magnetic resonance imaging, we isolated distinct response patterns in left PFC during source memory consistent with semantic analysis/cue specification (anterior ventrolateral), recollective monitoring (posterior dorsolateral and frontopolar), and phonological maintenance/rehearsal (posterior ventrolateral). Importantly, cue specification and recollective monitoring responses were not seen during item memory and were unaffected by retrieval success, demonstrating that the mere attempt to recollect episodic detail engages multiple control processes with different left PFC substrates.

Patterns of inter-joint coordination during a single-limb standing.

Past studies have documented contributions of multiple joints in maintaining a single-limb standing, but no reports on patterns of inter-joint coordination. It is also unknown whether such inter-joint coordination, if exists, depends on visual feedback. Eight health young volunteers took part in this study. The inter-joint coordination during a single-limb standing were examined using 3D joint kinematics. There were five testing trials with eyes open (EO) and five trials with eyes close (EC) conditions. During each trial the subject stood on the right leg on an even platform for 20 s while 3D kinematic data was recorded. Recorded data was processed for an "adjusted coefficient of multiple determinations (ACMD)" to evaluate the inter-joint similarities in joint motions. Under both EO and EC conditions moderate to good similarities were found in axial rotation between the ankle and hip joints, and between ankle inversion/eversion and hip axial rotation. This pattern of the inter-joint coordination might be a unique feature of biomechanical configuration of the lower extremity. The significant increases in joint rotations but maintained inter-joint coordination from EO to EC condition may indicate a minimal influence of vision on the inter-joint coordination. Future studies to test patients with pathological conditions in single-limb stance need to examine any alternation/impairment of the inter-joint coordination pattern.

Both viral transcription and replication are reduced when the rabies virus nucleoprotein is not phosphorylated.

Rabies virus nucleoprotein (N) plays vital roles in regulation of viral RNA transcription and replication by encapsidation of the nascent genomic RNA. Rabies virus N is phosphorylated, and previous studies demonstrated that mutation of the phosphorylated serine at position 389 to alanine resulted in reduction of viral transcription and/or replication of a rabies virus minigenome. In the present study, we mutated the serine (S) at position 389 to alanine (A), glycine (G), aspartic acid (D), asparagine (N), glutamic acid (E), and glutamine (Q) and examined the effects of these mutations on rabies virus transcription and replication in the minigenome. Furthermore, mutations from S to A, S to D, and S to E were also incorporated into the full-length infectious virus. Mutation of the serine to each of the other amino acids resulted in the synthesis of an unphosphorylated N and reduction of viral transcription and replication in the minigenome. Mutations from S to A and S to D also resulted in reduction of both viral transcription and replication in full-length infectious viruses. Growth curve studies indicated that production of the mutant virus with the S-to-A mutation (L16A) was as much as 10,000-fold less than that of the wild-type virus (L16). Northern blot hybridization with rabies virus gene probes revealed that the rates of viral transcription and replication were reduced by as much as 10-fold in the mutant viruses when the N was not phosphorylated. Interpretation of the data from the minigenome system and the full-length infectious virus indicates that phosphorylation of rabies virus N is necessary for replication. Further studies involving cycloheximide treatment of infected cells revealed that viral transcription was also reduced when the N was not phosphorylated. Taken together, these results provide definitive evidence that N phosphorylation plays an important role in the processes of rabies virus transcription and replication.

Rhabdovirus-based vectors with human immunodeficiency virus type 1 (HIV-1) envelopes display HIV-1-like tropism and target human dendritic cells.

We describe replication-competent, vaccine strain-based rabies viruses (RVs) that lack their own single glycoprotein and express, instead, a chimeric RV-human immunodeficiency virus type 1 (HIV-1) envelope protein composed of the ectodomain and transmembrane domains of HIV-1 gp160 and the cytoplasmic domain of RV G. The envelope proteins from both X4 (NL4-3)- and R5X4 (89.6)-tropic HIV-1 strains were utilized. These recombinant viruses very closely mimicked an HIV-1- like tropism, as indicated by blocking experiments. Infection was inhibited by SDF-1 on cells expressing CD4 and CXCR4 for both viruses, whereas RANTES abolished infection of cells expressing CCR5 in addition to CD4 in studies of the RV expressing HIV-1(89.6) Env. In addition, preincubation with soluble CD4 or monoclonal antibodies directed against HIV-1 gp160 blocked the infectivity of both G-deficient viruses but did not affect the G-containing RVs. Our results also indicated that the G-deficient viruses expressing HIV-1 envelope protein, in contrast to wild-type RV but similar to HIV-1, enter cells by a pH-independent pathway. As observed for HIV-1, the surrogate viruses were able to target human peripheral blood mononuclear cells, macrophages, and immature and mature human dendritic cells (DC). Moreover, G-containing RV-based vectors also infected mature human DC, indicating that infection of these cells is also supported by RV G. The ability of RV-based vectors to infect professional antigen-presenting cells efficiently further emphasizes the potential use of recombinant RVs as vaccines.

Stat3 beta inhibits gamma-globin gene expression in erythroid cells.

We demonstrated previously gamma-globin gene inhibition in K562 cells and primary erythroid progenitors treated with interleukin-6. Although several cis-acting elements have been identified in the globin promoters, the precise mechanism for cytokine-mediated globin gene regulation remains to be elucidated. In this report we demonstrate inhibitors of Stat3 phosphorylation abrogate interleukin-6-mediated gamma gene silencing in erythroid cells. DNA-protein binding studies established Stat3 interaction in the 5'-untranslated gamma-globin promoter region. Furthermore, co-transfection experiments with Stat3 beta demonstrate gamma promoter inhibition in a concentration-dependent manner, which was significantly reversed when the cognate Stat3-binding site in the 5'-untranslated region was mutated. These studies establish a novel mechanism for gamma gene silencing through the STAT signal transduction pathway.

Second-generation rabies virus-based vaccine vectors expressing human immunodeficiency virus type 1 gag have greatly reduced pathogenicity but are highly immunogenic.

Rabies virus (RV) vaccine strain-based vectors show great promise as vaccines against other viral diseases such as human immunodeficiency virus type 1 (HIV-1) infection and hepatitis C, but a low residual pathogenicity remains a concern for their use. Here we describe several highly attenuated second-generation RV-based vaccine vehicles expressing HIV-1 Gag. For this approach, we modified the previously described RV vaccine vector SPBN by replacing the arginine at position 333 (R333) within the RV glycoprotein (G) with glutamic acid (E333), deleting 43 amino acids of the RV G cytoplasmic domain (CD), or combining the R333 exchange and the CD deletion. In addition, we constructed a new RV vector that expresses HIV-1 Gag from an RV transcription unit upstream of the RV phosphoprotein gene (BNSP-Gag) instead of upstream of the G gene. As expected and as demonstrated for SPBN-Gag, all vaccine vehicles were apathogenic after peripheral administration. However, the new, second-generation vaccine vectors containing modifications in the RV G were also apathogenic after intracranial infection with 10(5) infectious particles, and BNSP-Gag produced a 50%-reduced mortality in mice. Of note, the observed attenuation of pathogenicity did not result in either the attenuation of the humoral response against the RV G or the previously observed robust cellular response against HIV-1 Gag. These findings demonstrate that very safe and highly effective RV-based vaccines can be constructed and further emphasize their potential utility as efficacious antiviral vaccines.

Intrarater Reliability of Functional Performance Tests for Subjects With Patellofemoral Pain Syndrome.

OBJECTIVE: Patellofemoral pain syndrome (PFPS) is a common clinical entity seen by the sports medicine specialist. The ultimate goal of rehabilitation is to return the patient to the highest functional level in the most efficient manner. Therefore, it is necessary to assess the progress of patients with PFPS using reliable functional performance tests. Our purpose was to evaluate the intrarater reliability of 5 functional performance tests in patients with PFPS. DESIGN AND SETTING: We used a test-retest reliability design in a clinic setting. SUBJECTS: Two groups of subjects were studied: those with PFPS (n = 29) and those with no known knee condition (n = 11). The PFPS group included 19 women and 10 men with a mean age of 27.6 +/- 5.3 years, height of 169.80 +/- 10.5 cm, and weight of 69.59 +/- 15.8 kg. The normal group included 7 women and 4 men with a mean age of 30.3 +/- 5.2 years, height of 169.55 +/- 9.9 cm, and weight 69.42 +/- 14.6 kg. MEASUREMENTS: The reliability of 5 functional performance tests (anteromedial lunge, step-down, single-leg press, bilateral squat, balance and reach) was assessed in 15 subjects with PFPS. Secondly, the relationship of the 5 functional tests to pain was assessed in 29 PFPS subjects using Pearson product moment correlations. The limb symmetry index (LSI) was calculated in the 29 PFPS subjects and compared with the group of 11 normal subjects. RESULTS: The 5 functional tests proved to have fair to high intrarater reliability. Intrarater reliability coefficients (ICC 3,1) ranged from.79 to.94. For the PFPS subjects, a statistical difference existed between limbs for the anteromedial lunge, step-down, single-leg press, and balance and reach. All functional tests correlated significantly with pain except for the bilateral squat; values ranged from.39 to.73. The average LSI for the PFPS group was 85%, while the average LSI for the normal subjects was 97%. CONCLUSIONS: The 5 functional tests proved to have good intrarater reliability and were related to changes in pain. Future research is needed to examine interrater reliability, validity, and sensitivity of these clinical tests.