Management of concussion symptoms utilizing Mechanical Diagnosis and Therapy: a case series.

OBJECTIVE: Concussions are a common condition in athletes leading to symptoms including headache, dizziness, and sometimes vestibular deficits. Concussion management typically involves rest and a gradual return to activity among other interventions. This case series includes three patients who were evaluated using Mechanical Diagnosis and Therapy (MDT) after sport-related injuries involving concussion-like symptoms. MDT is a system of evaluating patients using repeated movements and sustained positions to assess symptomatic and mechanical changes. RESULTS: Patients in this case series demonstrated rapid reduction of symptoms using variations of repeated cervical movements and sustained positions, which enabled them to return to play with a lasting resolution of symptoms. DISCUSSION/CONCLUSION: This highlights the importance of a classification system for the appropriate treatment of these cases who did not require management using concussion protocol, as they were classified as cervical derangement.

Smoking Pack Years and Eustachian Tube Dysfunction.

Objective: To determine the effect of smoking history on the risk of developing obstructive eustachian tube dysfunction (OETD). Study Design: Cross-sectional review. Setting: National database. Methods: Data from the National Health and Nutrition Examination Survey (1999 to present) was analyzed. OETD was defined as middle ear pressure less than -100 decapascals (daPa). Nonsmokers, current smokers, with tympanometry data were analyzed. Patients under the age of 18, with myringotomy tubes, or with a sinus problem/earache/cold in the past 24 hours were excluded. The relative risks (RRs) for developing OETD were calculated for nonsmokers versus smokers and those with greater versus less than 10, 20, and 30 pack years (py). Results: A total of 9472 patients met inclusion criteria (54.1% female, 75.9% non-Hispanic, mean age 43, 20.3% smokers). The RR of having OETD for smokers versus nonsmokers was 1.75 [95% confidence interval, CI: 1.45-2.11]. The RR of having OETD for patients with a 10+ py was 1.97 [95% CI 1.57-2.47], 20+ py was 2.29 [95% CI 1.76-2.95], and 30 py or greater was 2.08 [95% CI 1.49-2.90]. Conclusion: In this study, smoking roughly doubled the risk of developing OETD, as represented by a single measurement of negative middle ear pressure less than -100 daPa. The definition of OETD used in this study was limited, as it did not include symptomology, and more work is needed to examine additional covariates. However, these results may guide future research to better counsel and screen patients for OETD.

3D Genial Tubercle Anatomic Considerations in Genioglossus Advancement Surgery.

OBJECTIVE: To qualitatively describe variation in morphology of the genial tubercle and quantify the spatial relationship between the tubercle and genioglossus muscle. STUDY DESIGN: Case series. SETTING: Cadaver dissection. METHODS: Segmental sections of the mandible, with muscular attachments intact, were harvested from 18 fresh cadaver heads. Three-dimensional laser scans, with a resolution of 0.025 mm, were taken of each specimen with muscle attached and repeated after muscle removal. The genioglossus muscular attachment was measured relation to bony landmarks. RESULTS: The morphology of the genial tubercle varied, with anywhere from 1 large spine to 4 individual spines. However, all specimens had a distinguishable superior portion of the tubercle, where the genioglossus attached, and an inferior portion, where the geniohyoid attached. The height of the superior tubercle (ST) was 6.1 mm (95% confidence inerval [CI]: 5.7-6.5). The height of the genioglossus muscle above the peak amplitude of the ST was 4.3 mm (3.8-4.9), but only 2.5 mm (2.0-3.0) below. On average, 64.4% (58.6-70.2) of the height of the genioglossus muscle attachment was above the peak. Overall, 19.5% (14.1-25.0) of the muscle surface area extended beyond the boundaries of the tubercle. CONCLUSION: The genioglossus muscle attachment originates from the superior genial tubercle, which has a variable topography and amplitude. However, the muscle is not centered on the spines-more of the muscular fibers attach above the spine as compared to below. This new data may explain the genioglossus advancement "miss rate"-failure to advance muscle on initial osteotomy-of 39-78% reported in the literature.

Patient Satisfaction with Nonopioid Postoperative Analgesia in Head and Neck Surgery: A Prospective Randomized Trial.

OBJECTIVE: To evaluate patients' satisfaction with opioid versus opioid-sparing postoperative analgesia in patients undergoing outpatient head and neck surgery. STUDY DESIGN: Prospective randomized trial. SETTING: Tertiary care academic hospital. METHODS: Adult patients undergoing outpatient head and neck surgery were randomly assigned to 1 of 3 analgesic regimens. First- and second-line medications were the following by group (1) Hydrocodone-acetaminophen with ibuprofen, (2) ibuprofen with hydrocodone-acetaminophen, and (3) ibuprofen with acetaminophen. Preoperative counseling was provided to patients regarding expected pain and proper medication use. Postoperative questionnaires were administered to assess satisfaction. RESULTS: One hundred three patients were enrolled in the study (mean age, 56.5 years; women, 75 [73%]). The mean satisfaction score with the pain regimen assigned was similar between the 3 groups (scale 0-10, [7.7, 8.3, 8.5, P = .46]). A similar percentage of patients in each group reported that surgery was more painful than anticipated (25%, 32%, 26%, P = .978), and a similar percentage of patients reported willingness to utilize the same analgesic regimen following future surgeries (75%, 83%, 76%, P = .682). Additional questions evaluating the side effect profile, maximum and minimum pain scores, and difficulty of recovery were not statistically different between the 3 groups. CONCLUSION: In the postoperative population for outpatient head and neck surgeries, there was no significant difference in patient satisfaction and pain control between the opioid and nonopioid arms. Providers should discuss opioid-sparing regimens preoperatively with patients and describe them as effective in providing adequate pain control without a significant impact on patient's perception of care.

A Contemporary Review of Trachea, Nose, and Ear Cartilage Bioengineering and Additive Manufacturing.

The complex structure, chemical composition, and biomechanical properties of craniofacial cartilaginous structures make them challenging to reconstruct. Autologous grafts have limited tissue availability and can cause significant donor-site morbidity, homologous grafts often require immunosuppression, and alloplastic grafts may have high rates of infection or displacement. Furthermore, all these grafting techniques require a high level of surgical skill to ensure that the reconstruction matches the original structure. Current research indicates that additive manufacturing shows promise in overcoming these limitations. Autologous stem cells have been developed into cartilage when exposed to the appropriate growth factors and culture conditions, such as mechanical stress and oxygen deprivation. Additive manufacturing allows for increased precision when engineering scaffolds for stem cell cultures. Fine control over the porosity and structure of a material ensures adequate cell adhesion and fit between the graft and the defect. Several recent tissue engineering studies have focused on the trachea, nose, and ear, as these structures are often damaged by congenital conditions, trauma, and malignancy. This article reviews the limitations of current reconstructive techniques and the new developments in additive manufacturing for tracheal, nasal, and auricular cartilages.

Viral infection disrupts intestinal homeostasis via Sting-dependent NF-κB signaling in Drosophila.

Host-microbe interactions influence intestinal stem cell (ISC) activity to modulate epithelial turnover and composition. Here, we investigated the functional impacts of viral infection on intestinal homeostasis and the mechanisms by which viral infection alters ISC activity. We report that Drosophila A virus (DAV) infection disrupts intestinal homeostasis in Drosophila by inducing sustained ISC proliferation, resulting in intestinal dysplasia, loss of gut barrier function, and reduced lifespan. We found that additional viruses common in laboratory-reared Drosophila also promote ISC proliferation. The mechanism of DAV-induced ISC proliferation involves progenitor-autonomous epidermal growth factor receptor (EGFR) signaling, c-Jun N-terminal kinase (JNK) activity in enterocytes, and requires Sting-dependent nuclear factor κB (NF-κB) (Relish) activity. We further demonstrate that activating Sting-Relish signaling is sufficient to induce ISC proliferation, promote intestinal dysplasia, and reduce lifespan in the absence of infection. Our results reveal that viral infection can significantly disrupt intestinal physiology, highlight a novel role for Sting-Relish signaling, and support a role for viral infection in aging.

New Frontiers in Nonheme Enzymatic Oxyferryl Species.

Non-heme mononuclear iron dependent (NHM-Fe) enzymes exhibit exceedingly diverse catalytic reactivities. Despite their catalytic versatilities, the mononuclear iron centers in these enzymes show a relatively simple architecture, in which an iron atom is ligated with 2-4 amino acid residues, including histidine, aspartic or glutamic acid. In the past two decades, a common high-valent reactive iron intermediate, the S = 2 oxoferryl (Fe(IV)-oxo or Fe(IV)=O) species, has been repeatedly discovered in NHM-Fe enzymes containing a 2-His-Fe or 2-His-1-carboxylate-Fe center. However, for 3-His/4-His-Fe enzymes, no common reactive intermediate has been identified. Recently, we have spectroscopically characterized the first S = 1 Fe(IV) intermediate in a 3-His-Fe containing enzyme, OvoA, which catalyzes a novel oxidative carbon-sulfur bond formation. In this review, we summarize the broad reactivities demonstrated by S = 2 Fe(IV)-oxo intermediates, the discovery of the first S = 1 Fe(IV) intermediate in OvoA and the mechanistic implication of such a discovery, and the intrinsic reactivity differences of the S = 2 and the S = 1 Fe(IV)-oxo species. Finally, we postulate the possible reasons to utilize an S = 1 Fe(IV) species in OvoA and their implications to other 3-His/4-His-Fe enzymes.

The Long-Term Effect of COVID-19 Infection on Body Composition.

BACKGROUND: The effect of COVID-19 infection versus the indirect effect of the pandemic on body composition remains unclear. This study investigates the long-term changes in body composition in COVID-19 survivors compared to a contemporary control group. METHOD: This is a prospective study involving adults who underwent a pre-pandemic whole-body DXA scan (DXA#1) between 2017 and 2019. Participants were asked to return for a repeat whole-body DXA scan (DXA#2) after the pandemic. Detailed data were collected including their medical and COVID-19 history. Inflammation markers and fasting lipids were measured. For those participants who experienced a COVID-19 infection between the two DXAs, DXA#2 was acquired at least one year after COVID-19 infection. RESULTS: Overall, 160 adults were enrolled; 32.5% females, 51.8% non-white, with mean age of 43.2 years. Half (n = 80) of the participants experienced a COVID-19 infection between their two DXA scans (COVID-19+ group), and the other half had never had COVID-19. COVID-19-negative participants displayed an increase in annualized trunk fat (g) [922.5 vs. 159.7; p = 0.01], total fat (g) [1564.3 vs. 199.9; p = 0.2], and LBM (g) [974.9 vs. -64.5; p = 0.0002] when compared to the COVID-19+ group. However, among the COVID-19+ group, no differences were seen in annualized trunk fat, total fat mass, or LBM between those with PASC and without (p > 0.05). CONCLUSION: During the pandemic, both the COVID-19 survivors and the COVID-19-negative group exhibited increases in weight, total fat, and trunk fat, likely associated with pandemic-linked lifestyle modifications. However, only COVID-19 survivors displayed a decline in lean body mass over the same period, regardless of PASC symptoms.

Composite Thickness and Stiffness Analysis of the Nasal Septum.

Background: The nasal septum supports the structure of the nose and is frequently manipulated during septorhinoplasty. Objective: To compare measurements of thickness and compressive Young's modulus (YM) between different regions of nasal septa from human anatomic specimens. Study Design: Case series. Methods: Cartilaginous septa from human anatomic specimens were dissected. Septum thickness was measured at 24 points with regular intervals using a digital caliper. Compressive YM was determined at 14 regions using a force gauge. Two-tailed student's t-tests were used to compare the average thickness and YM between different regions. Results: Septa from 40 human anatomic specimens were included, with age ranging from 50 to 89. Fifty percent of specimens were female. The mean (standard deviation) thickness of the septum was 1.75 (0.76) mm. The mean YM was 2.38 (1.29) MPa. The septum was thickest near the maxillary crest (3.09 [1.17] mm) and the keystone area (2.52 [0.91] mm) and thinnest near the anterior septal angle (1.29 [0.58] mm). The septum was most stiff posteriorly (2.90 [1.32] MPa) and least stiff anteriorly (1.80 [1.15] MPa). Conclusion: The nasal septum is thickest posteriorly, inferiorly, and along its bony edges. The septum is stiffest posteriorly, ventrally, and along its bony edges.

Case report: Molecular profiling facilitates the diagnosis of a challenging case of lung cancer with choriocarcinoma features.

Accurate diagnoses are crucial in determining the most effective treatment across different cancers. In challenging cases, morphology-based traditional pathology methods have important limitations, while molecular profiling can provide valuable information to guide clinical decisions. We present a 35-year female with lung cancer with choriocarcinoma features. Her disease involved the right lower lung, brain, and thoracic lymph nodes. The pathology from brain metastasis was reported as "metastatic choriocarcinoma" (a germ cell tumor) by local pathologists. She initiated carboplatin and etoposide, a regimen for choriocarcinoma. Subsequently, her case was assessed by pathologists from an academic cancer center, who gave the diagnosis of "adenocarcinoma with aberrant expression of ß-hCG" and finally pathologists at our hospital, who gave the diagnosis of "poorly differentiated carcinoma with choriocarcinoma features". Genomic profiling detected a KRAS G13R mutation and transcriptomics profiling was suggestive of lung origin. The patient was treated with carboplatin/paclitaxel/ipilimumab/nivolumab followed by consolidation radiation therapy. She had no evidence of progression to date, 16 months after the initial presentation. The molecular profiling could facilitate diagnosing of challenging cancer cases. In addition, chemoimmunotherapy and local consolidation radiation therapy may provide promising therapeutic options for patients with lung cancer exhibiting choriocarcinoma features.

Multiplexed serum biomarkers to discriminate nonviable and ectopic pregnancy.

OBJECTIVE: To evaluate combinations of candidate biomarkers to develop a multiplexed prediction model for identifying the viability and location of an early pregnancy. In this study, we assessed 24 biomarkers with multiple machine learning-based methodologies to assess if multiplexed biomarkers may improve the diagnosis of normal and abnormal early pregnancies. DESIGN: A nested case-control design evaluated the predictive ability and discrimination of biomarkers in patients at risk of early pregnancy failure in the first trimester to classify viability and location. SETTING: Three university hospitals. PATIENTS: A total of 218 individuals with pain and/or bleeding in early pregnancy: 75 had an ongoing intrauterine gestation; 68 had ectopic pregnancies (EPs); and 75 had miscarriages. INTERVENTIONS: Serum levels of 24 biomarkers were assessed in the same patients. Multiple machine learning-based methodologies to evaluate combinations of these top candidates to develop a multiplexed prediction model for the identification of a nonviable pregnancy (ongoing intrauterine pregnancy vs. miscarriage or EP) and an EP (EP vs. ongoing intrauterine pregnancy or miscarriage). MAIN OUTCOME MEASURES: The predicted classification using each model was compared with the actual diagnosis, and sensitivity, specificity, positive predictive value, negative predictive value, conclusive classification, and accuracy were calculated. RESULTS: Models using classification regression tree analysis using 3 (pregnancy-specific beta-1-glycoprotein 3 [PSG3], chorionic gonadotropin-alpha subunit, and pregnancy-associated plasma protein-A) biomarkers were able to predict a maximum sensitivity of 93.3% and a maximum specificity of 98.6%. The model with the highest accuracy was 97.4% (with 70.2% receiving classification). Models using an overlapping group of 3 (soluble fms-like tyrosine kinase-1, PSG3, and tissue factor pathway inhibitor 2) biomarkers achieved a maximum sensitivity of 98.5% and a maximum specificity of 95.3%. The model with the highest accuracy was 94.4% (with 65.6% receiving classification). When the models were used simultaneously, the conclusive classification increased to 72.7% with an accuracy of 95.9%. The predictive ability of the biomarkers in the random forest produced similar test characteristics when using 11 predictive biomarkers. CONCLUSION: We have demonstrated a pool of biomarkers from divergent biological pathways that can be used to classify individuals with potential early pregnancy loss. The biomarkers choriogonadotropin alpha, pregnancy-associated plasma protein-A, and PSG3 can be used to predict viability, and soluble fms-like tyrosine kinase-1, tissue factor pathway inhibitor 2, and PSG3 can be used to predict pregnancy location.

Patterns of Discordance Between Clinical and Pathologic Stage in Head and Neck Cancer.

OBJECTIVE: To enhance understanding in patterns of discordance between clinical and pathological T and N staging in multiple sites of head and neck squamous cell cancer. METHODS: A retrospective cohort of 580 newly diagnosed and surgically treated head and neck squamous cell carcinoma patients from a single institution over a 10-year period are presented. Clinical and pathologic staging are compared. RESULTS: Notably, 33% of cases had staging discordance. Overall Cohen's kappa agreement was κ = 0.55 (moderate agreement). Highly discordant site stages with κ < 0.45 included: T2 oral cavity, T2 oropharynx, T3 larynx, and N1 lymph node. T2-4 oral cavity cancers were often overstaged, and more than one-third of T3 larynx cancers were understaged. Highly concordant site stages with κ>0.65 included: T1 larynx, T4 oropharynx, N0 lymph node, and N3 lymph node. CONCLUSION: There exists a quantifiable and, in certain sites, clinically relevant pattern of discordance between clinical and pathologic staging. Tumor board multidisciplinary evaluation can highlight these discrepancies and aide in limiting effects on treatment decisions. However, discordant staging can affect the interpretation and application of prognostication, treatment, and data accuracy. Further investigation is warranted to improve clinical staging accuracy in areas of highest discordance. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Pharmacodynamic effects following co-administration of cannabinoids and opioids: a scoping review of human experimental studies.

BACKGROUND: Cannabinoids are increasingly used in the management of chronic pain. Although analgesic potential has been demonstrated, cannabinoids interact with a range of bodily functions that are also influenced by chronic pain medications, including opioids. OBJECTIVE: We performed a scoping review of literature on the pharmacodynamic effects following the co-administration of cannabinoids and opioids. METHODS: We systematically searched EMBASE, PubMed, and PsycINFO for studies that experimentally investigated the co-effects of cannabinoids and opioids in human subjects. Available evidence was summarized by clinical population and organ system. A risk of bias assessment was performed. RESULTS: A total of 16 studies met the inclusion criteria. Study populations included patients with chronic non-cancer and cancer pain on long-term opioid regimens and healthy young adults without prior exposure to opioids who were subject to experimental nociceptive stimuli. Commonly administered cannabinoid agents included Δ9-tetrahydrocannabinol and/or cannabidiol. Co-administration of cannabinoids and opioids did not consistently improve pain outcomes; however, sleep and mood benefits were observed in chronic pain patients. Increased somnolence, memory and attention impairment, dizziness, gait disturbance, and nauseousness and vomiting were noted with co-administration of cannabinoids and opioids. Cardiorespiratory effects following co-administration appeared to vary according to duration of exposure, population type, and prior exposure to cannabinoids and opioids. CONCLUSIONS: The available evidence directly investigating the pharmacodynamic effects following co-administration of cannabinoids and opioids for non-analgesic outcomes is scarce and suffers from a lack of methodological reporting. As such, further research in this area with comprehensive methodologic reporting is warranted.

Lip Wedge Resection with Orbicularis Oris Plication for Facial Paralysis: A Novel Technique.

Introduction: Oral incompetence (OI) following facial nerve injury or sacrifice remains a frustrating problem for patients and clinicians alike. Dynamic procedures for facial paralysis often do not fully address OI and static surgeries are frequently needed. Current static options frequently involved multiple facial incisions. Methods: We describe a novel technique to address OI due to lower division facial nerve paralysis and report outcomes in an initial series of patients. Results: OI symptoms improved in 94% of patients following a single-stage surgery. Revision was required in one patient with subsequent resolution of symptoms. Major complications (19%) included persistent OI, wound dehiscence, and bothersome lip "bulk". Conclusion: Lip wedge resection with orbicular oris plication resolves OI in facial paralysis patients with the added benefit of only a single incision on the face.

Introduction : L'incompétence orale après une blessure ou un sacrifice des nerfs faciaux demeure un problème frustrant, tant pour les patients que pour les cliniciens. En cas de paralysie faciale, il n'est pas rare que les interventions dynamiques ne corrigent pas toute l'incompétence orale, et des interventions statiques sont souvent nécessaires. Les options statiques actuelles exigent souvent de multiples incisions faciales. Méthodologie : Les chercheurs décrivent une nouvelle technique pour corriger une incompétence orale en raison d'une paralysie de la partie inférieure des nerfs faciaux et rendent compte des résultats auprès d'une série initiale de patients. Résultats : Les symptômes d'incompétence orale ont diminué chez 94 % des patients après une chirurgie en un temps. Un patient a dû subir une révision, puis les symptômes se sont résorbés. Les complications majeures (19 %) incluaient une incompétence orale persistante, la déhiscence de la plaie et un « volume ¼ dérangeant de la lèvre. Conclusion : La résection en coin par plicature de l'orbiculaire des lèvres résout l'incompétence orale en cas de paralysie faciale et a l'avantage supplémentaire de nécessiter une seule incision sur le visage.

Treatment and Mortality Following Cancer Diagnosis Among People With Non-affective Psychotic Disorders in Ontario, Canada: A Retrospective Cohort Study.

BACKGROUND AND HYPOTHESIS: People with psychotic disorders have a higher risk of mortality following cancer diagnosis, compared to people without psychosis. The extent to which this disparity is influenced by differences in cancer-related treatment is currently unknown. We hypothesized that, following a cancer diagnosis, people with psychotic disorders were less likely to receive treatment and were at higher risk of death than those without psychosis. STUDY DESIGN: We constructed a retrospective cohort of cases of non-affective psychotic disorder (NAPD) and a general population comparison group, using Ontario Health (OH) administrative data. We identified cases of all cancers diagnosed between 1995 and 2019 and obtained information on cancer-related treatment and mortality. Cox proportional hazards models were used to compare the probability of having a consultation with an oncologist and receiving cancer-related treatment, adjusting for tumor site and stage. We also compared the rate of all-cause and cancer-related mortality between the two groups, adjusting for tumor site. STUDY RESULTS: Our analytic sample included 24 944 people diagnosed with any cancer. People with NAPD were less likely to receive treatment than people without psychosis (HR = 0.87, 95% CI = 0.82, 0.91). In addition, people with NAPD had a greater risk of death from any cause (HR = 1.68, 95% CI = 1.60, 1.76), compared to people without NAPD. CONCLUSIONS: The lower likelihood of receiving cancer treatment reflects disparities in accessing cancer care for people with psychotic disorders, which may partially explain the higher mortality risk following cancer diagnosis. Future research should explore mediating factors in this relationship to identify targets for reducing health disparities.

A cholesterol-binding bacterial toxin provides a strategy for identifying a specific Scap inhibitor that blocks lipid synthesis in animal cells.

Lipid synthesis is regulated by the actions of Scap, a polytopic membrane protein that binds cholesterol in membranes of the endoplasmic reticulum (ER). When ER cholesterol levels are low, Scap activates SREBPs, transcription factors that upregulate genes for synthesis of cholesterol, fatty acids, and triglycerides. When ER cholesterol levels rise, the sterol binds to Scap, triggering conformational changes that prevent activation of SREBPs and halting synthesis of lipids. To achieve a molecular understanding of how cholesterol regulates the Scap/SREBP machine and to identify therapeutics for dysregulated lipid metabolism, cholesterol-mimetic compounds that specifically bind and inhibit Scap are needed. To accomplish this goal, we focused on Anthrolysin O (ALO), a pore-forming bacterial toxin that binds cholesterol with a specificity and sensitivity that is uncannily similar to Scap. We reasoned that a small molecule that would bind and inhibit ALO might also inhibit Scap. High-throughput screening of a ~300,000-compound library for ALO-binding unearthed one molecule, termed UT-59, which binds to Scap's cholesterol-binding site. Upon binding, UT-59 triggers the same conformation changes in Scap as those induced by cholesterol and blocks activation of SREBPs and lipogenesis in cultured cells. UT-59 also inhibits SREBP activation in the mouse liver. Unlike five previously reported inhibitors of SREBP activation, UT-59 is the only one that acts specifically by binding to Scap's cholesterol-binding site. Our approach to identify specific Scap inhibitors such as UT-59 holds great promise in developing therapeutic leads for human diseases stemming from elevated SREBP activation, such as fatty liver and certain cancers.

Altered mitochondrial respiration in peripheral blood mononuclear cells of post-acute sequelae of SARS-CoV-2 infection.

Peripheral blood mononuclear cells (PBMC) mitochondrial respiration was measured ex vivo from participants without a history of COVID (n = 19), with a history of COVID and full recovery (n = 20), and with PASC (n = 20). Mean mitochondrial basal respiration, ATP-linked respiration, maximal respiration, spare respiration capacity, ATP-linked respiration, and non-mitochondrial respiration were highest in COVID + PASC+ (p ≤ 0.04). Every unit increase in non-mitochondrial respiration, ATP-linked respiration, basal respiration, spare respiration capacity, and maximal respiration increased the predicted odds of PASC between 1 % and 6 %. Mitochondrial dysfunction in PBMCs may be contributing to the etiology of PASC.

Selective C-H Halogenation of Alkenes and Alkynes Using Flavin-Dependent Halogenases.

Single component flavin-dependent halogenases (FDHs) possess both flavin reductase and FDH activity in a single enzyme. We recently reported that the single component FDH AetF catalyzes site-selective bromination and iodination of a variety of aromatic substrates and enantioselective bromolactonization and iodoetherification of styrenes bearing pendant carboxylic acid or alcohol substituents. Given this inherent reactivity and selectivity, we explored the utility of AetF as catalyst for alkene and alkyne C-H halogenation. We find that AetF catalyzes halogenation of a range of 1,1-disubstituted styrenes, often with high stereoselectivity. Despite the utility of haloalkenes for cross-coupling and other applications, accessing these compounds in a stereoselective manner typically requires functional group interconversion processes, and selective halogenation of 1,1'-disubstituted olefins remains rare. We also establish that AetF and homologues of this enzyme can halogenate terminal alkynes. Mutagenesis studies and deuterium kinetic isotope effects are used to support a mechanistic proposal involving covalent catalysis for halogenation of unactivated alkynes by AetF homologues. These findings expand the scope of FDH catalysis and continue to show the unique utility of single component FDHs for biocatalysis.