Multisite Mpox Infection and Viral Dynamics Among Persons With HIV in Metro Atlanta.

The 2022 mpox outbreak primarily involved sexual transmission among men who have sex with men and disproportionately affected persons with human immunodeficiency virus (HIV). We examined viral dynamics and clinical features in a cohort evaluated for mpox infection at a comprehensive HIV clinic in Atlanta, Georgia. Viral DNA was found in 8 oropharyngeal and 5 anorectal specimens among 10 mpox cases confirmed by lesion swab polymerase chain reaction. Within-participant anatomic site of lowest cycle threshold (Ct) value varied, and lower Ct values were found in oropharyngeal and anorectal swabs when corresponding symptoms were present. This provides insight into mpox infection across multiple anatomic sites among people with HIV.

Low body mass index is a risk factor for hyperkalaemia associated with angiotensin converting enzyme inhibitors and angiotensin II receptor blockers treatments.

WHAT IS KNOWN AND OBJECTIVE: Angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) represent the cornerstones of hypertension and congestive heart failure treatment. Risk factors for hyperkalaemia associated with ACEI and ARB are chronic kidney disease and concomitant medications which increase serum potassium level. Body mass index (BMI) also affects pharmacokinetics of ACEI and ARB and potassium disposition. We evaluated the relationship between BMI and hyperkalaemia associated with ACEI and ARB treatments. METHODS: Study design is a retrospective case-control analysis. Patients who had been prescribed ACEI or ARB between June 2015 and June 2017 at Tokyo Women's Medical University, Medical Center East, were included. Patient clinical background was collected from medical records. Hyperkalaemia was defined as serum potassium above 5.5 meq/L. The concomitant use of ACEI and ARB, aldosterone antagonists, direct renin inhibitor, sulfamethoxazole-trimethoprim and non-steroidal anti-inflammatory drugs (NSAIDs) was regarded as hyperkalaemia-inducing medications. The relationship between BMI and hyperkalaemia associated with ACEI and ARB treatments was assessed using multivariable logistic regression analysis. RESULTS AND DISCUSSION: The study included 2987 patients aged 70.1 ± 12.9 years, 61.0% were men, and BMI was 23.8 ± 4.4 kg/m2 . The incidence of hyperkalaemia was 7.8%. Multivariable logistic regression analysis revealed that age >65 years, low BMI, diabetes, history of treatment for hyperkalaemia, serum sodium <135 meq/L, eGFR <30 mL/min/1.73m2 and the concomitant use of hyperkalaemia-inducing medications were independent risk factors for hyperkalaemia associated with ACEI and ARB. WHAT IS NEW AND CONCLUSION: This study demonstrated that BMI provides useful information for the identification of potential risk for hyperkalaemia associated with ACEI and ARB treatments.

Different X-linked KDM5C mutations in affected male siblings: is maternal reversion error involved?

Genetic reversion is the phenomenon of spontaneous gene correction by which gene function is partially or completely rescued. However, it is unknown whether this mechanism always correctly repairs mutations, or is prone to error. We investigated a family of three boys with intellectual disability, and among them we identified two different mutations in KDM5C, located at Xp11.22, using whole-exome sequencing. Two affected boys have c.633delG and the other has c.631delC. We also confirmed de novo germline (c.631delC) and low-prevalence somatic (c.633delG) mutations in their mother. The two mutations are present on the same maternal haplotype, suggesting that a postzygotic somatic mutation or a reversion error occurred at an early embryonic stage in the mother, leading to switched KDM5C mutations in the affected siblings. This event is extremely unlikely to arise spontaneously (with an estimated probability of 0.39-7.5 × 10(-28) ), thus a possible reversion error is proposed here to explain this event. This study provides evidence for reversion error as a novel mechanism for the generation of somatic mutations in human diseases.

A quantitative and humane tail bleeding assay for efficacy evaluation of antihaemophilic factors in haemophilia A mice.

The tail bleeding model using haemophilic mice has been used as one of the standard assays for efficacy evaluation of novel antihaemophilic therapies at the preclinical level. A number of different configurations and endpoints have been proposed in the literature for this model, hindering interlaboratory comparisons. A particular configuration, known as the tail bleeding survival assay (TBS), adopted by several groups, involves measuring the ability of conscious haemophilic mice to survive exsanguination following tail transection. Major limitations to this configuration include ethical constraints and impaired quantitative determinations. The aim of this study was to standardize and validate a quantitative haemostatic assay for evaluation of antihaemophilic therapies employing an alternative to TBS, which involves a more humane endpoint associated with stable clot formation. Haemophilic mice were treated with vehicle or different doses of two antihaemophilic reference products licensed in Brazil. The haemostatic response was evaluated by our quantitative tail bleeding haemostatic assay (qTBA) over a period of 120 min and then quantified by dose-response modelling. We demonstrate that our qTBA method allows a direct relationship between the number of animals which achieved full haemostatic response and the dosage of both antihaemophilic factors evaluated over 120 min. In addition, the method sensitivity is suitable to demonstrate the conversion from a severe to a moderate haemophilia phenotype. Our proposed qTBA is easy to implement and constitutes an alternative and more ethical endpoint, which could be effectively used as a surrogate to the commonly employed survival endpoint, allowing quantitative haemostatic response evaluation associated with stable clot formation.

Otosyphilis.

Otosyphilis can be challenging to diagnose, but, if left unrecognized, it may cause irreversible damage. An immunologic interplay between syphilis and human immunodeficiency virus (HIV) makes coinfection likely and may predispose people with HIV to neurosyphilis. In this study, we present a case of a man in his 50s with hearing loss and vertigo diagnosed with otosyphilis as well as a new diagnosis of HIV. This case and corresponding discussion serve to inform the noninfectious disease-trained clinician of the symptoms, diagnostics, and treatment options for otosyphilis as well as to discuss the relationship between HIV and syphilis and demonstrate the importance of disease recognition.

Magnetic-field-induced shape recovery by reverse phase transformation.

Large magnetic-field-induced strains have been observed in Heusler alloys with a body-centred cubic ordered structure and have been explained by the rearrangement of martensite structural variants due to an external magnetic field. These materials have attracted considerable attention as potential magnetic actuator materials. Here we report the magnetic-field-induced shape recovery of a compressively deformed NiCoMnIn alloy. Stresses of over 100 MPa are generated in the material on the application of a magnetic field of 70 kOe; such stress levels are approximately 50 times larger than that generated in a previous ferromagnetic shape-memory alloy. We observed 3 per cent deformation and almost full recovery of the original shape of the alloy. We attribute this deformation behaviour to a reverse transformation from the antiferromagnetic (or paramagnetic) martensitic to the ferromagnetic parent phase at 298 K in the Ni45Co5Mn36.7In13.3 single crystal.

A Call to Action: Integration of Buprenorphine Prescribing Into the Care of Persons With Human Immunodeficiency Virus and Opioid Use Disorder.

During the coronavirus disease 2019 (COVID-19) pandemic, we also experienced a worsening opioid overdose epidemic. Untreated opioid use disorder (OUD) in persons with human immunodeficiency virus (HIV) is associated with worse HIV-related outcomes. Buprenorphine is a safe, evidence-based medication for OUD and is effective in reducing opioid craving and overdose and improving outcomes along the HIV care continuum. Despite the longstanding evidence supporting the benefits of buprenorphine, there remains an implementation gap in the uptake of buprenorphine prescribing in HIV care settings. To improve integration of OUD care and HIV primary care, we recommend (1) all HIV clinicians obtain a buprenorphine waiver, (2) teaching on OUD should be integrated into infectious diseases and HIV continuing medical education, and (3) previously validated models of integrated care should be leveraged to urgently expand access to buprenorphine for persons with HIV and OUD.

Bone-destructive osseous arteriovenous fistula at the jugular bulb mimicking a glomus jugular tumor.

BACKGROUND: Some reports have described intraosseous arteriovenous fistulas showing osteolytic changes, but an osseous arteriovenous fistula (AVF) at the jugular bulb showing extensive bone destruction is a very rare disease. CASE DESCRIPTION: A 60-year-old man presented with pulsatile tinnitus and right facial nerve palsy. Radiological imaging showed a large homogenously enhanced osteolytic lesion at the right jugular foramen. A cerebral angiogram showed a high-flow vascular lesion of the jugular bulb associated with retrograde sinus reflux, resulting in venous congestion of the deep venous system. These findings led us to misdiagnose this lesion as a glomus jugular tumor. However, combined arterial and venous angiography after transarterial embolization revealed the precise angioarchitecture, and we finally diagnosed this lesion as a high-flow osseous AVF at the jugular bulb. We performed transvenous embolization using a triple catheter technique. The lesion was successfully obliterated, and the 6-months angiogram showed no recurrence. CONCLUSION: A rare case of high flow osseous AVF at the jugular bulb associated with osteolytic changes in the surrounding bony structure is reported. Although many hypervascular lesions at the jugular bulb are glomus tumors, bone destructive osseous AVF at the jugular bulb should be considered.

Absence of the Anterior Communicating Artery on Selective MRA is Associated with New Ischemic Lesions on MRI after Carotid Revascularization.

BACKGROUND AND PURPOSE: ICA-selective MRA using a pencil beam presaturation pulse can accurately visualize anterior communicating artery flow. We evaluated the impact of anterior communicating artery flow on the perioperative hemodynamic status and new ischemic lesions after carotid revascularization. MATERIALS AND METHODS: Eighty-three patients with carotid artery stenosis were included. We assessed anterior communicating artery flow using ICA-selective MRA. The preoperative hemodynamic status was measured using SPECT. We also measured the change in regional cerebral oxygen saturation after temporary ICA occlusion. New ischemic lesions were evaluated by DWI on the day after treatment. RESULTS: Anterior communicating artery flow was detected in 61 patients, but it was not detected in 22 patients. Preoperative cerebrovascular reactivity was significantly higher in patients with (versus without) anterior communicating artery flow with a mean peak systolic velocity of ≥200 cm/s (39.6% [SD, 23.8%] versus 25.2% [SD, 16.4%]; P = .030). The decrease in mean regional cerebral oxygen saturation was significantly greater in patients without (versus with) anterior communicating artery flow (8.5% [SD, 5.6%] versus 3.7% [SD, 3.8%]; P = .002). New ischemic lesions after the procedure were observed in 23 patients. The multivariate logistic regression analysis revealed that anterior communicating artery flow (OR, 0.07; 95% CI, 0.012-0.45; P = .005) was associated with new ischemic lesions. CONCLUSIONS: The absence of anterior communicating artery flow influenced the perioperative hemodynamic status in patients with carotid stenosis and was associated with an increased incidence of new ischemic lesions after carotid revascularization.

Cooperation between mDia1 and ROCK in Rho-induced actin reorganization.

The small GTPase Rho induces the formation of actin stress fibres and mediates the formation of diverse actin structures. However, it remains unclear how Rho regulates its effectors to elicit such functions. Here we show that GTP-bound Rho activates its effector mDia1 by disrupting mDia1's intramolecular interactions. Active mDia1 induces the formation of thin actin stress fibres, which are disorganized in the absence of activity of the Rho-associated kinase ROCK. Moreover, active mDia1 transforms ROCK-induced condensed actin fibres into structures reminiscent of Rho-induced stress fibres. Thus mDia1 and ROCK work concurrently during Rho-induced stress-fibre formation. Intriguingly, mDia1 and ROCK, depending on the balance of the two activities, induce actin fibres of various thicknesses and densities. Thus Rho may induce the formation of different actin structures affected by the balance between mDia1 and ROCK signalling.

[Subscapular elastofibroma].

Elastofibroma is a tumor that is localized mainly at the subscapular region. We report 2 cases of subscapular elastofibromas. Case 1, 75-year-old woman was seen at the hospital because of a left dorsal tumor. Computed tomography (CT) scan revealed the tumor of 6 cm in diameter in the inferior angle of left scapula. The patient underwent excision of the tumor. Case 2, 90-year-old man underwent excision a tumor of 5 cm in diameter in the inferior angle of right scapula simultaneously with the operation of right lung cancer. Histological examinations showed increased elastic fiber with elastica van Gieson staining. These specimens confirmed the diagnosis of elastofibroma There have been no signs of recurrence after surgery.

Multigenerational cortical inheritance of the Rax2 protein in orienting polarity and division in yeast.

Diploid yeast cells repeatedly polarize and bud from their poles, probably because of highly stable marks of unknown composition. Here, Rax2, a membrane protein, was shown to behave as such a mark. The Rax2 protein itself was inherited immutably at the cell cortex for multiple generations, and Rax2 was shown to have a half-life exceeding several generations. The persistent inheritance of cortical protein markers would provide a means to couple a cell's history to the future development of a precise morphogenetic form.

Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase.

The actin cytoskeleton undergoes extensive remodeling during cell morphogenesis and motility. The small guanosine triphosphatase Rho regulates such remodeling, but the underlying mechanisms of this regulation remain unclear. Cofilin exhibits actin-depolymerizing activity that is inhibited as a result of its phosphorylation by LIM-kinase. Cofilin was phosphorylated in N1E-115 neuroblastoma cells during lysophosphatidic acid-induced, Rho-mediated neurite retraction. This phosphorylation was sensitive to Y-27632, a specific inhibitor of the Rho-associated kinase ROCK. ROCK, which is a downstream effector of Rho, did not phosphorylate cofilin directly but phosphorylated LIM-kinase, which in turn was activated to phosphorylate cofilin. Overexpression of LIM-kinase in HeLa cells induced the formation of actin stress fibers in a Y-27632-sensitive manner. These results indicate that phosphorylation of LIM-kinase by ROCK and consequently increased phosphorylation of cofilin by LIM-kinase contribute to Rho-induced reorganization of the actin cytoskeleton.

Magnetic anisotropy in Ni-Fe-Ga-Co ferromagnetic shape memory alloys in the single-variant state.

The effects of the addition of Co on the magnetic anisotropy in Ni(55-x)Fe(18)Ga(27)Co(x) (x = 1-6) single-variant ferromagnetic shape memory alloys have been investigated. By the addition of Co from 1 to 6 at.%, the Curie temperature T(C) is increased from 318 to 405 K, keeping the martensitic transformation temperatures above room temperature. As a result, the value of the uniaxial magnetic anisotropy constant |K(u)| at 300 K increases with increasing x of the Co concentration and the martensite phase of Ni(49)Fe(18)Ga(27)Co(6) exhibits a relatively high value of |K(u)| = 1.15 × 10(5) J m(-3) at 300 K. With increasing Co concentration, on the other hand, the c axis changes from the magnetic easy axis to the hard axis at 4.2 K, that is, the sign of K(u) is reversed from positive to negative between 2 and 3 at.% Co. Furthermore, K(u) in Ni(53)Fe(18)Ga(27)Co(2) is positive below 100 K and negative above 100 K up to T(C), reducing the magnetic anisotropy around 200 K. From the present results, it is evident that the magnetic anisotropy of Ni(55-x)Fe(18)Ga(27)Co(x) (x = 1-6) single-variant ferromagnetic shape memory alloys is very sensitive to Co concentration and also temperature.

Stress-assisted large magnetic-field-induced strain in single-variant Co-Ni-Ga ferromagnetic shape memory alloy.

The magnetic anisotropy and the magnetic-field-induced strain (MFIS) in a single-variant Co(47.5)Ni(22.5)Ga(30.0) ferromagnetic shape memory alloy (FSMA) have been investigated. From the magnetization curves for the single crystal, the hard c-axis was confirmed, and the uniaxial magnetic anisotropy constant K(u) at 300 K was evaluated to be -1.07 × 10(6) erg cm(-3) for the single-variant Co(47.5)Ni(22.5)Ga(30.0) martensite phase. The magnitude of compressive shear stress for the variant rearrangement was estimated to be 6.0-7.5 MPa from the stress-strain curves. An assisted stress τ(assist) of 6.0 MPa was applied before applying a magnetic field, and then a magnetic stress τ(mag) of 0.3 MPa was added. As a result, a large MFIS of about 7.6 % was obtained at room temperature in the martensite phase of the single-variant Co(47.5)Ni(22.5)Ga(30.0).

Localization of Parotid Gland Tumors in Relation to the Intraparotid Facial Nerve on 3D Double-Echo Steady-State with Water Excitation Sequence.

BACKGROUND AND PURPOSE: Reliable preoperative facial nerve mapping may help avoid or minimize facial nerve injury during parotid tumor resection. The purpose of this study was to investigate the diagnostic performance of the 3D double-echo steady-state with water excitation sequence in localizing parotid gland tumors through direct visualization of the intraparotid facial nerve in comparison with indirect methods of estimating the facial nerve location. MATERIALS AND METHODS: We retrospectively reviewed 91 parotid gland tumors in 90 patients who underwent surgical resection and preoperative MR imaging, including the 3D double-echo steady-state with water excitation sequence. The tumor locations were categorized as deep or superficial on the basis of direct and 3 indirect methods: the facial nerve line, retromandibular vein, and Utrecht line. Surgical localization was considered the criterion standard. The diagnostic performance for localizing deep lobe lesions using direct and indirect methods was calculated and compared using the McNemar test. RESULTS: Surgical localization confirmed 75 superficial lesions and 16 deep lesions. The interobserver variability of the 3D double-echo steady-state with water excitation sequence was excellent (κ = 0.870). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for localizing deep lobe lesions using the 3D double-echo steady-state with water excitation method were 97.8%, 87.5%, 100%, 100%, and 97.4%, respectively. These findings were significantly higher than the facial nerve line in sensitivity, the retromandibular vein in sensitivity, and the Utrecht line in accuracy and specificity (P < .05). Overall, the direct method was the most accurate, sensitive, and specific in localizing parotid gland tumors. CONCLUSIONS: We can achieve higher diagnostic performance in localizing parotid gland tumors by directly visualizing the intraparotid facial nerve using the 3D double-echo steady-state with water excitation sequence compared with indirect methods.

DWI for Monitoring the Acute Response of Malignant Gliomas to Photodynamic Therapy.

BACKGROUND AND PURPOSE: Photodynamic therapy is a novel treatment that provides effective local control, but little is known about photodynamic therapy-induced changes on MR imaging. The aim of this study was to assess the utility of DWI and ADC in monitoring the response of malignant gliomas to photodynamic therapy. MATERIALS AND METHODS: Time-dependent changes in DWI and ADC values after photodynamic therapy were analyzed in a group that received photodynamic therapy in comparison with a group that did not. RESULTS: Twenty-four patients were enrolled (photodynamic therapy, n = 14; non-photodynamic therapy, n = 10). In all patients who received photodynamic therapy, linear high signals on DWI in the irradiated area were detected adjacent to the resection cavity and were 5-7 mm in depth from 1 day posttreatment and disappeared in about 30 days without any neurologic deterioration. The non-photodynamic therapy group did not show this change. The photodynamic therapy group had significantly lower ADC values from 1 day posttreatment (P < .001), which increased steadily and disappeared by 30 days. There was no decline or time-dependent change in ADC values in the non-photodynamic therapy group. CONCLUSIONS: The acute response of malignant gliomas to photodynamic therapy was detected as linear high signals on DWI and as a decrease in ADC values. These findings were asymptomatic and transient. Although the photodynamic therapy-induced acute response on MR imaging disappeared after approximately 30 days, it may be helpful for confirming the photodynamic therapy-irradiated area.

Etiology-Specific Mineralization Patterns in Patients with Labyrinthitis Ossificans.

BACKGROUND AND PURPOSE: Our aim was to identify whether specific patterns of ossification in labyrinthitis ossificans are associated with the known risk factors. Labyrinthitis ossificans has been described as sequela of prior temporal bone trauma, prior infection, and other disorders including sickle cell disease. Specific patterns of mineralization in the membranous labyrinth associated with these risk factors has not been previously described. MATERIALS AND METHODS: This was a retrospective study evaluating temporal bone CT scans at our institution from November 2005 to May 2018 in patients with labyrinthitis ossificans. Membranous labyrinthine structures evaluated for ossification included the following: basal, middle, and apical cochlear turns; lateral, posterior, and superior semicircular canals; and the vestibule for both ears in all patients. These structures were assigned a severity score, 0-4, based on degree of mineralization. Clinical records were reviewed for potential labyrinthitis ossificans risk factors. Basic descriptive statistics and a mixed model were used to correlate the degree and patterns of ossification with clinical history. RESULTS: Forty-four patients (58 ears) with labyrinthitis ossificans were identified and evaluated. The most common risk factors were chronic otomastoiditis (n = 18), temporal bone surgery (n = 9), temporal bone trauma (n = 6), sickle cell disease (n = 5), and meningitis (n = 4). For all etiologies, the semicircular canals were most severely affected, and the vestibule was the least. In patients with prior temporal bone surgery, significantly greater mineralization was seen in the basal turn of the cochlea (P = .027), the vestibule (P = .001), and semicircular canals (P < .001-.008). No significant pattern was identified in patients with meningitis, sickle cell disease, or trauma. CONCLUSIONS: Significant patterns of mineralization in labyrinthitis ossificans were observed in patients with prior temporal bone surgery. For all etiologies, the semicircular canals were most severely affected. No significant mineralization pattern was observed in patients with chronic otomastoiditis, meningitis, sickle cell disease, or prior temporal bone trauma.