The microbiota coordinates diurnal rhythms in innate immunity with the circadian clock.

Environmental light cycles entrain circadian feeding behaviors in animals that produce rhythms in exposure to foodborne bacteria. Here, we show that the intestinal microbiota generates diurnal rhythms in innate immunity that synchronize with feeding rhythms to anticipate microbial exposure. Rhythmic expression of antimicrobial proteins was driven by daily rhythms in epithelial attachment by segmented filamentous bacteria (SFB), members of the mouse intestinal microbiota. Rhythmic SFB attachment was driven by the circadian clock through control of feeding rhythms. Mechanistically, rhythmic SFB attachment activated an immunological circuit involving group 3 innate lymphoid cells. This circuit triggered oscillations in epithelial STAT3 expression and activation that produced rhythmic antimicrobial protein expression and caused resistance to Salmonella Typhimurium infection to vary across the day-night cycle. Thus, host feeding rhythms synchronize with the microbiota to promote rhythms in intestinal innate immunity that anticipate exogenous microbial exposure.

Development and Pilot of an Mpox Severity Scoring System.

Clinical severity scores facilitate comparisons to understand risk factors for severe illness. For the 2022 multinational monkeypox clade IIb virus outbreak, we developed a 7-item Mpox Severity Scoring System (MPOX-SSS) with initial variables refined by data availability and parameter correlation. Application of MPOX-SSS to the first 200 patients diagnosed with mpox revealed higher scores in those treated with tecovirimat, presenting >3 days after symptom onset, and with CD4 counts <200 cells/mm3. For individuals evaluated repeatedly, serial scores were concordant with clinical observations. The pilot MPOX-SSS demonstrated good discrimination, distinguished change over time, and identified higher scores in expected groups.

How the Orthodox Features of Orthopoxviruses Led to an Unorthodox Mpox Outbreak: What We've Learned, and What We Still Need to Understand.

Orthopoxviruses have repeatedly confounded expectations in terms of the clinical illness they cause and their patterns of spread. Monkeypox virus (MPXV), originally characterized in the late 1950s during outbreaks among captive primates, has been recognized since the 1970s to cause human disease (mpox) in West and Central Africa, where interhuman transmission has largely been associated with nonsexual, close physical contact. In May 2022, a focus of MPXV transmission was detected, spreading among international networks of gay, bisexual, and other men who have sex with men. The outbreak grew in both size and geographic scope, testing the strength of preparedness tools and public health science alike. In this article we consider what was known about mpox before the 2022 outbreak, what we learned about mpox during the outbreak, and what continued research is needed to ensure that the global public health community can detect, and halt further spread of this disease threat.

Low CD4 Count or Being Out of Care Increases the Risk for Mpox Hospitalization Among People With Human Immunodeficiency Virus and Mpox.

Human immunodeficiency virus (HIV)-associated immunosuppression may increase the risk of hospitalization with mpox. Among persons diagnosed with mpox in the state of Georgia, we characterized the association between hospitalization with mpox and HIV status. People with HIV and a CD4 count <350 cells/mm3 or who were not engaged in HIV care had an increased risk of hospitalization.

Structural brain plasticity and inflammation are independently related to changes in depressive symptoms six months after an index ECT course.

BACKGROUND: Electroconvulsive therapy (ECT) is effective for treatment-resistant depression and leads to short-term structural brain changes and decreases in the inflammatory response. However, little is known about how brain structure and inflammation relate to the heterogeneity of treatment response in the months following an index ECT course. METHODS: A naturalistic six-month study following an index ECT course included 20 subjects with treatment-resistant depression. Upon conclusion of the index ECT course and again after six months, structural magnetic resonance imaging scans and peripheral inflammation measures [interleukin-6 (IL-6), IL-8, tumor necrosis factor (TNF-α), and C-reactive protein] were obtained. Voxel-based morphometry processed with the CAT-12 Toolbox was used to estimate changes in gray matter volume. RESULTS: Between the end of the index ECT course and the end of follow-up, we found four clusters of significant decreases in gray matter volume (p < 0.01, FWE) and no regions of increased volume. Decreased HAM-D scores were significantly related only to reduced IL-8 level. Decreased volume in one cluster, which included the right insula and Brodmann's Area 22, was related to increased HAM-D scores over six months. IL-8 levels did not mediate or moderate the relationship between volumetric change and depression. CONCLUSIONS: Six months after an index ECT course, multiple regions of decreased gray matter volume were observed in a naturalistic setting. The independent relations between brain volume and inflammation to depressive symptoms suggest novel explanations of the heterogeneity of longer-term ECT treatment response.

Assessing the properties of patient-specific treatment effect estimates from causal forest algorithms under essential heterogeneity.

BACKGROUND: Treatment variation from observational data has been used to estimate patient-specific treatment effects. Causal Forest Algorithms (CFAs) developed for this task have unknown properties when treatment effect heterogeneity from unmeasured patient factors influences treatment choice - essential heterogeneity. METHODS: We simulated eleven populations with identical treatment effect distributions based on patient factors. The populations varied in the extent that treatment effect heterogeneity influenced treatment choice. We used the generalized random forest application (CFA-GRF) to estimate patient-specific treatment effects for each population. Average differences between true and estimated effects for patient subsets were evaluated. RESULTS: CFA-GRF performed well across the population when treatment effect heterogeneity did not influence treatment choice. Under essential heterogeneity, however, CFA-GRF yielded treatment effect estimates that reflected true treatment effects only for treated patients and were on average greater than true treatment effects for untreated patients. CONCLUSIONS: Patient-specific estimates produced by CFAs are sensitive to why patients in real-world practice make different treatment choices. Researchers using CFAs should develop conceptual frameworks of treatment choice prior to estimation to guide estimate interpretation ex post.

Canadian Consensus Guidelines for the Diagnosis and Treatment of Autoimmune Encephalitis in Adults.

Autoimmune encephalitis is increasingly recognized as a neurologic cause of acute mental status changes with similar prevalence to infectious encephalitis. Despite rising awareness, approaches to diagnosis remain inconsistent and evidence for optimal treatment is limited. The following Canadian guidelines represent a consensus and evidence (where available) based approach to both the diagnosis and treatment of adult patients with autoimmune encephalitis. The guidelines were developed using a modified RAND process and included input from specialists in autoimmune neurology, neuropsychiatry and infectious diseases. These guidelines are targeted at front line clinicians and were created to provide a pragmatic and practical approach to managing such patients in the acute setting.

Twenty year analysis of professional men's rugby union knee injuries from the English premiership shows high rates and burden.

OBJECTIVES: To determine the rates, severity and burden of knee injuries in professional male rugby union from the English Premiership. METHODS: Injury and exposure data were captured over 20 seasons using a prospective cohort design. Knee injury incidence, days' absence and burden were recorded for each injury type and by pitch surface type for match and training. RESULTS: The rate of knee injury in matches was 9.8/1000 hours (95% CIs 9.3-10.3). Mean days lost were 50 (95% CI 46 to 53) in matches and 51 (95% CI 44 to 57) in training. In matches, medial collateral ligament injuries were the most common, while anterior cruciate ligament (ACL) injuries had the highest mean severity and burden. There was no significant change in the count of knee injuries over time; however, average severity increased significantly (annual change: 2.18 days (95% CI 1.60 to 2.77); p<0.001). The incidence of match knee injury was 44% higher on artificial pitches than grass pitches (incidence rate ratio: 1.44 (95% CI 1.21 to 1.69); p<0.01), with no significant difference in severity between surfaces. In matches, the tackle was the event most commonly associated with knee injuries for all diagnoses, except ACL injuries (running). In training, running was a more common injury event than the tackle. CONCLUSION: Knee injuries in matches are common and severe in English professional men's rugby union. Despite an increased focus on player conditioning and injury prevention throughout the study period, rates of knee injury remained stable, and resulting days' absence increased. New strategies for the prevention of knee injuries should be considered a priority.

ICD-10 diagnosis codes in electronic health records do not adequately capture fracture complexity for proximal humerus fractures.

BACKGROUND: The ability to do comparative effectiveness research (CER) for proximal humerus fractures (PHF) using data in electronic health record (EHR) systems and administrative claims databases was enhanced by the 10th revision of the International Classification of Diseases (ICD-10), which expanded the diagnosis codes for PHF to describe fracture complexity including displacement and the number of fracture parts. However, these expanded codes only enhance secondary use of data for research if the codes selected and recorded correctly reflect the fracture complexity. The objective of this project was to assess the accuracy of ICD-10 diagnosis codes documented during routine clinical practice for secondary use of EHR data. METHODS: A sample of patients with PHFs treated by orthopedic providers across a large, regional health care system between January 1, 2016, and December 31, 2018, were retrospectively identified from the EHR. Four fellowship-trained orthopedic surgeons reviewed patient radiographs and recorded the Neer Classification characteristics of displacement, number of parts, and fracture location(s). The fracture characteristics were then reviewed by a trained coder, and the most clinically appropriate ICD-10 diagnosis code based on the number of fracture parts was assigned. We assessed congruence between ICD-10 codes documented in the EHR and radiograph-validated codes, and assessed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for EHR-documented ICD-10 codes. RESULTS: There were 761 patients with unilateral, closed PHF who met study inclusion criteria. On average, patients were 67 years of age and 77% were female. Based on radiograph review, 37% were 1-part fractures, 42% were 2-part, 11% were 3-part, and 10% were 4-part fractures. Of the EHR diagnosis codes recorded during clinical practice, 59% were "unspecified" fracture diagnosis codes that did not identify the number of fracture parts. Examination of fracture codes revealed PPV was highest for 1-part (PPV = 0.66, 95% confidence interval [CI] 0.60-0.72) and 4-part fractures (PPV = 0.67, 95% CI 0.13-1.00). CONCLUSIONS: Current diagnosis coding practices do not adequately capture the fracture complexity needed to conduct subgroup analysis for PHF. Conclusions drawn from population studies or large databases using ICD-10 codes for PHF classification should be interpreted within this limitation. Future studies are warranted to improve diagnostic coding to support large observational studies using EHR and administrative claims data.

Successful completion of orthodontic therapy in a patient with osteopetrosis: Case Report.

INTRODUCTION: Orthodontic therapy in patients with osteopetrosis (OP) of the jaws has typically been contraindicated owing to the presence of poorly perfused and extremely compact bone, and the potential risk for infection and osteomyelitis. As such, completed orthodontic cases in association with OP have rarely been published. PATIENT CONCERNS: A patient aged 14 years 6 months, with no known diagnosis of OP, sought orthodontic assessment for anterior crowding. CLINICAL FINDINGS: The patient exhibited a straight facial profile and increased mandibular facial height, competent lips, shallow mentolabial sulcus with mild mentalis strain, flat/reverse smile arc and wide buccal corridors on smiling. PRIMARY DIAGNOSIS: The patient had a Class I incisor relationship on Class I skeletal bases with bilateral Class I molars and Class II canine relationships. This was complicated by a crossbite involving the lateral incisors and a Bolton discrepancy due to small maxillary lateral incisors. A radiologic assessment revealed polyostotic OP of the oromaxillofacial complex. INTERVENTIONS: Treatment consisted of maxillary and mandibular fixed orthodontic therapy, bite turbos and elastics to level and align the dentition. Extractions of permanent teeth were not needed. OUTCOMES: At the conclusion of treatment, there was a slight left Class II malocclusion, with incomplete intercuspation on the left side due to tooth size discrepancy, possibly attributed to inadequate elastics compliance and the presence of osteopetrotic bone. The treatment was completed in 3 years, 1 year longer than anticipated. CONCLUSION: This report represents the second published account of a patient with OP successfully managed with comprehensive orthodontic care and without osseous complications. Obtaining cephalometric measurements on OP-affected patients may be imprecise owing to the presence of extremely dense bone and difficulty to identify bony landmarks. To reduce osteopetrotic sequelae, attending clinicians should consider reduced exertional orthodontic forces and closely monitor patients for adverse alveolar events.

Oral manifestations of mpox (monkeypox).

The zoonotic infectious disease mpox (previously known as monkeypox) is caused by the monkeypox virus (MPXV) from the Poxviridae family. Presently, mpox is receiving worldwide attention because of its emergence in countries that have never previously documented the illness, resulting in a public health emergency. MPXV is transmitted via human-to-human contact, and sexual contact is especially implicated in spread of the disease. Affected individuals experience fever, headache, malaise, and early lymphadenopathy, followed by a secondary mucotaneous rash. Oral ulcers and perioral papules may be the first evidence of the disease. Although there are numerous articles in medical publications documenting the cutaneous presentations of mpox, there is limited information in the dental literature regarding oral lesions. The objective of this article is to review the oral manifestations of mpox and strategies for management of the disease.

Severe radiographic artifact created by a large fenestration of the skin and labial mucosa following placement of a plate piercing: a case report.

The presence of facial jewelry and medical devices within a radiographic field of view may promote the formation of artifacts that challenge diagnostic interpretation. The objective of this article is to describe a previously unreported radiographic anomaly produced by an oral piercing site below the lower lip. This unusual artifact masqueraded as a severe resorptive defect, dental caries, or cervical abfraction and occurred following removal of an extremely large labret below the lower lip and subsequent acquisition of a radiographic image. The radiolucency was ultimately attributed to an extensive aperture below the lower lip created by a series of sequentially larger soft tissue expanders. Clinicians should seek correlation of atypical radiographic presentations with soft tissue defects secondary to injury or intentional oral piercing.

Dental implant failure possibly attributed to embedded pencil graphite: first clinical report.

Implant failures have been associated with a diversity of etiologic processes, predominately arising from bone loss (peri-implantitis) due to inadequate maintenance of oral hygiene or excess luting agents. The aim of this article is to report a novel case of the apparent failure of a dental implant to undergo osseointegration in the presence of submerged pencil graphite. Practitioners are advised to carefully evaluate the clinical and radiographic site of a proposed implant for occult foreign substances. Embedded pencil graphite in the jawbone may promote a foreign body reaction and should be considered in the list of possible contributing factors to dental implant complications.

Diminutive compound odontoma in a child: a case report with emphasis on early detection.

The odontoma is regarded as a hamartomatous process of the jaws. Most are discovered as an incidental radiographic finding, averaging 15 mm in size. This report describes a case of a diminutive odontoma that was surgically removed before the onset of eruptive and pathologic consequences. A compilation of documented complications and syndromes associated with odontomas is also presented.

Unanticipated costs associated with interscalene nerve catheters for shoulder surgery.

BACKGROUND: Regional anesthesia has become a mainstay of analgesia following shoulder arthroscopic and reconstructive procedures. Local anesthetic can be injected in the perineural space of the brachial plexus by a single shot or continuously by an indwelling catheter. Although previous studies have compared efficacy and direct cost of single shot to catheters, few have evaluated unanticipated costs of ongoing care or complications. Pulmonary complications can lead to unexpected admissions and emergency department visits. The purpose of the study was to identify unplanned hospital admissions or emergency department visits related to regional anesthesia after shoulder surgery and determine the additional associated costs. METHODS: A series of 1888 shoulder surgeries were identified in 1856 unique patients at a single, large academic center. As part of an interscalene nerve catheter program, a continuous interscalene block (CIB) was given to 1728 patients, whereas 160 patients had a single-shot interscalene block (SSIB). A hospital-employed quality control nurse contacted all patients receiving a CIB at 1, 2, 7, and 14 days following surgery. All emergency department visits and readmissions were recorded, and the associated billing charges were reviewed for the inpatient and any outpatient visits immediately preceding or immediately following the readmission. The regional average Medicare fee schedule was used to determine a cost for these episodes of care. RESULTS: Of the 1728 patients who had CIB, 10 patients were readmitted following open or arthroscopic surgery or presented to the emergency department in the immediate postoperative period for pulmonary compromise. No patient in the SSIB group had an emergency department visit or readmission. The average age of the 10 patients with readmission was 60 years (7 females, 3 males). The majority were diagnosed with hypoxemia on admission (R09.02). Length of stay during readmission ranged from 0 to 4 days, with 1 patient requiring admission to the intensive care unit. The average cost of admission to the hospital or visit to the emergency department was $6849 (range, $1988-$19,483). These costs were primarily related to chest radiographs and electrocardiogram (9/10), chest computed tomography (CT) with contrast (3/10), and head CT (2/10). CONCLUSION: Although uncommon, unanticipated pulmonary complications after CIB can result in significant cost compared to SSIB. The indirect costs of pulmonary workup after readmission or emergency department workup may be overlooked if only considering direct costs, such as medication charges, medical supplies, and physician fees.

Spindle cell lipoma of the buccal mucosa: Uncommon finding in an older adult.

OBJECTIVE: This article reports a case of a longstanding, slowly enlarging intraoral spindle cell lipoma (SCL) that had become increasingly painful during mastication. BACKGROUND: The SCL represents an uncommon variant of the conventional lipoma. There is limited information regarding this lesion in the gerodontologic literature. MATERIALS AND METHODS: A 68-year-old patient underwent an excisional biopsy of a 9-mm slightly yellow papule along the buccal mucosa. RESULTS: The surgical specimen was composed of mature adipocytes with abundant spindle cell populations and was diagnosed as a SCL. CONCLUSIONS: Timely removal of the SCL may reduce the incidence of clinical and surgical complications, particularly in older adults. The management of a SCL is complete excision, and recurrence is rare. Lesions must be carefully distinguished microscopically from its malignant counterpart, the spindle cell liposarcoma.

Idiopathic bone cavity mimicking a botryoid odontogenic cyst: A rare radiographic presentation in an older adult.

OBJECTIVES: This report describes an unusual case of a multilocular idiopathic bone cavity (IBC) that presented as a botryoid odontogenic cyst situated between the mandibular lateral incisor and canine in an older adult. BACKGROUND: The IBC represents an intraosseous concavity that appears radiographically as a unilocular or multilocular radiolucent lesion found in various skeletal sites, including the jaw. Atypical cases of gnathic IBC have not been appreciated in the gerodontologic literature. MATERIALS AND METHODS: The teeth adjacent to the bony lesion had normal pulpal responses to cold. A full-thickness flap was elevated and provided a direct entry into a bony concavity, which was devoid of an epithelial lining and fluid. RESULTS: The lack of a cystic lining within the empty osseous lesion following surgical entry, concomitant with the vital pulpal status of the proximal teeth, led to a diagnosis of an IBC. The bony walls underwent curettage and copious irrigation prior to primary closure. A 10-month follow-up revealed partial evidence of osseous repair. The patient will continue to be monitored. CONCLUSION: Timely surgical intervention of central lesions of the jaws may improve clinical outcomes. Variants of the IBC should be included in the differential diagnosis of multilocular lesions, particularly in the geriatric population.

Pseudopathologic findings on panoramic radiographs and utility of follow-up cone beam computed tomographic scans: a case series.

Conventional radiography is the mainstay for evaluation of developmental and pathologic disorders of oral and maxillofacial structures. Occasionally, clinicians may experience diagnostic pitfalls during interpretation of these imaging modalities. The aim of this article is to present 4 cases of pseudopathologic disorders found on intraoral and panoramic radiographs. Subsequent use of cone beam computed tomographic (CBCT) imaging determined that the initial concerning findings represented anatomical or radiographic anomalies rather than pathologic processes. Supplemental use of CBCT scans may enhance diagnostic assessment, possibly reducing the need for surgical intervention, and elucidate structurally compromised regions of the jaw that could predispose it to fracture.

What every dentist needs to know about in-house clear aligner therapy.

Clear aligner therapy (CAT) has gained popularity in recent years. As technological advancements increase within the field of dentistry, clinicians have opted to prouce orthodontic appliances within their own offices or clinics, often referred to as in-house CAT. Construction of in-house aligners utilizes 3-dimensional printing devices, potentially offering practitioners enhanced control and improving patient comfort. The aim of this article is to review the materials, methods, advantages, disadvantages, and procedural outcomes associated with the fabrication of aligners within a dental office or clinic.

Interim Guidance for Prevention and Treatment of Monkeypox in Persons with HIV Infection - United States, August 2022.

Monkeypox virus, an orthopoxvirus sharing clinical features with smallpox virus, is endemic in several countries in Central and West Africa. The last reported outbreak in the United States, in 2003, was linked to contact with infected prairie dogs that had been housed or transported with African rodents imported from Ghana (1). Since May 2022, the World Health Organization (WHO) has reported a multinational outbreak of monkeypox centered in Europe and North America, with approximately 25,000 cases reported worldwide; the current outbreak is disproportionately affecting gay, bisexual, and other men who have sex with men (MSM) (2). Monkeypox was declared a public health emergency in the United States on August 4, 2022.† Available summary surveillance data from the European Union, England, and the United States indicate that among MSM patients with monkeypox for whom HIV status is known, 28%-51% have HIV infection (3-10). Treatment of monkeypox with tecovirimat as a first-line agent is available through CDC for compassionate use through an investigational drug protocol. No identified drug interactions would preclude coadministration of tecovirimat with antiretroviral therapy (ART) for HIV infection. Pre- and postexposure prophylaxis can be considered with JYNNEOS vaccine, if indicated. Although data are limited for monkeypox in patients with HIV, prompt diagnosis, treatment, and prevention might reduce the risk for adverse outcomes and limit monkeypox spread. Prevention and treatment considerations will be updated as more information becomes available.