The effects of alternate-day fasting on sleep and physical activity in poor sleeping adults: A randomized control trial.

Utilizing a randomized control design, 42 healthy adults (22.5 ± 2.8 years) participated in alternate-day modified fasting over a 12-day treatment period. Assessments of sleep included sleep time, efficiency, latency and wake after sleep onset, and assessments of physical activity included steps, energy expenditure, sedentary time, time spent in light physical activity and time spent in moderate-to-vigorous activity. Additional measurements included body composition and mood. The alternate-day modified fasting group consumed 25.8% ± 0.3% fewer calories compared with the control group (p = 0.03). There were no differences between groups for change in body mass index (p = 0.87), total fat mass (p = 0.91) or total lean mass (p = 0.88). Daily energy expenditure did not differ between groups (p = 0.11). On fast days, participants spent 34.5 ± 12.7 more minutes sedentary (p = 0.01), took 1100 ± 362 fewer steps (p < 0.01), and engaged in 27.2 ± 8.4 fewer minutes of moderate-to-vigorous physical activity (p = 0.00) compared with non-fasting days. Sleep duration, efficiency, latency or wake after sleep onset were not different between conditions (p = 0.92, p = 0.10, p = 0.09 and p = 0.66, respectively). We conclude that alternate-day modified fasting does not alter sleep time, efficiency, latency or wake after sleep onset in people reporting poor sleep quality, and does not alter overall physical activity. Although average daily physical activity is not altered, fasting in this manner does tend to result in more sedentary time and less physical activity with compensation on non-fasting days.

Secondary Sphere Lewis Acid Activated Heme Superoxo Adducts Mimic Crucial Non-Covalent Interactions in IDO/TDO Heme Dioxygenases.

Heme enzymes play a central role in a medley of reactivities within a wide variety of crucial biological systems. Their active sites are highly decorated with pivotal evolutionarily optimized non-covalent interactions that precisely choreograph their biological functionalities with specific regio-, stereo-, and chemo-selectivities. Gaining a clear comprehension of how such weak interactions within the active sites control reactivity offers powerful information to be implemented into the design of future therapeutic agents that target these heme enzymes. To shed light on such critical details pertaining to tryptophan dioxygenating heme enzymes, this study investigates the indole dioxygenation reactivities of Lewis acid-activated heme superoxo model systems, wherein an unprecedented kinetic behavior is revealed. In that, the activated heme superoxo adduct is observed to undergo indole dioxygenation with the intermediacy of a non-covalently organized precursor complex, which forms prior to the rate-limiting step of the overall reaction landscape. Spectroscopic and theoretical characterization of this precursor complex draws close parallels to the ternary complex of heme dioxygenases, which has been postulated to be of crucial importance for successful 2,3-dioxygenative cleavage of indole moieties.

Sensory-Behavioral Deficits in Parkinson's Disease: Insights from a 6-OHDA Mouse Model.

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the striatum, predominantly associated with motor symptoms. However, non-motor deficits, particularly sensory symptoms, often precede motor manifestations, offering a potential early diagnostic window. The impact of non-motor deficits on sensation behavior and the underlying mechanisms remains poorly understood. In this study, we examined changes in tactile sensation within a Parkinsonian state by employing a mouse model of PD induced by 6-hydroxydopamine (6-OHDA) to deplete striatal dopamine (DA). Leveraging the conserved mouse whisker system as a model for tactile-sensory stimulation, we conducted psychophysical experiments to assess sensory-driven behavioral performance during a tactile detection task in both the healthy and Parkinson-like states. Our findings reveal that DA depletion induces pronounced alterations in tactile sensation behavior, extending beyond expected motor impairments. We observed diverse behavioral deficits, spanning detection performance, task engagement, and reward accumulation, among lesioned individuals. While subjects with extreme DA depletion consistently showed severe sensory behavioral deficits, others with substantial DA depletion displayed minimal changes in sensory behavior performance. Moreover, some exhibited moderate degradation of behavioral performance, likely stemming from sensory signaling loss rather than motor impairment. The implementation of a sensory detection task is a promising approach to quantify the extent of impairments associated with DA depletion in the animal model. This facilitates the exploration of early non-motor deficits in PD, emphasizing the importance of incorporating sensory assessments in understanding the diverse spectrum of PD symptoms.

MULTIPLE DISTINCT TIMESCALES OF RAPID SENSORY ADAPATION IN THE THALAMOCORTICAL CIRCUIT.

Numerous studies have shown that neuronal representations in sensory pathways are far from static but are instead strongly shaped by the complex properties of the sensory inputs they receive. Adaptation dynamically shapes the neural signaling that underlies our perception of the world yet remains poorly understood. We investigated rapid adaptation across timescales from hundreds of milliseconds to seconds through simultaneous multi-electrode recordings from the ventro-posteromedial nucleus of the thalamus (VPm) and layer 4 of the primary somatosensory cortex (S1) in male and female anesthetized mice in response to controlled, persistent whisker stimulation. Observations in VPm and S1 reveal a degree of adaptation that progresses through the pathway. Signatures of two distinct timescales of rapid adaptation in the firing rates of both thalamic and cortical neuronal populations were revealed, also reflected in the synchrony of the thalamic population and in the thalamocortical synaptic efficacy that was measured in putatively monosynaptically connected thalamocortical pairs. Controlled optogenetic activation of VPm further demonstrated that the longer timescale adaptation observed in S1 is likely inherited from slow decreases in thalamic firing rate and synchrony. Despite the degraded sensory responses, adaptation resulted in a shift in coding strategy that favors theoretical discrimination over detection across the observed timescales of adaptation. Overall, although multiple mechanisms contribute to rapid adaptation at distinct timescales, they support a unifying framework on the role of adaptation in sensory processing.

Cortical Networks Relating to Arousal Are Differentially Coupled to Neural Activity and Hemodynamics.

Even in the absence of specific sensory input or a behavioral task, the brain produces structured patterns of activity. This organized activity is modulated by changes in arousal. Here, we use wide-field voltage imaging to establish how arousal relates to cortical network voltage and hemodynamic activity in spontaneously behaving head-fixed male and female mice expressing the voltage-sensitive fluorescent FRET sensor Butterfly 1.2. We find that global voltage and hemodynamic signals are both positively correlated with changes in arousal with a maximum correlation of 0.5 and 0.25, respectively, at a time lag of 0 s. We next show that arousal influences distinct cortical regions for both voltage and hemodynamic signals. These include a broad positive correlation across most sensory-motor cortices extending posteriorly to the primary visual cortex observed in both signals. In contrast, activity in the prefrontal cortex is positively correlated to changes in arousal for the voltage signal while it is a slight net negative correlation observed in the hemodynamic signal. Additionally, we show that coherence between voltage and hemodynamic signals relative to arousal is strongest for slow frequencies below 0.15 Hz and is near zero for frequencies >1 Hz. We finally show that coupling patterns are dependent on the behavioral state of the animal with correlations being driven by periods of increased orofacial movement. Our results indicate that while hemodynamic signals show strong relations to behavior and arousal, these relations are distinct from those observed by voltage activity.

Molecular and Functional Profiling of Gαi as an Intracellular pH Sensor.

Heterotrimeric G proteins (Gα, Gß and Gγ) act downstream of G-protein-coupled receptors (GPCRs) to mediate signaling pathways that regulate various physiological processes and human disease conditions. Previously, human Gαi and its yeast homolog Gpa1 have been reported to function as intracellular pH sensors, yet the pH sensing capabilities of Gαi and the underlying mechanism remain to be established. Herein, we identify a pH sensing network within Gαi, and evaluate the consequences of pH modulation on the structure and stability of the G-protein. We find that changes over the physiological pH range significantly alter the structure and stability of Gαi-GDP, with the protein undergoing a disorder-to-order transition as the pH is raised from 6.8 to 7.5. Further, we find that modulation of intracellular pH in HEK293 cells regulates Gαi-Gßγ release. Identification of key residues in the pH-sensing network allowed the generation of low pH mimetics that attenuate Gαi-Gßγ release. Our findings, taken together, indicate that pH-dependent structural changes in Gαi alter the agonist-mediated Gßγ dissociation necessary for proper signaling.

Prevention and resolution of headaches occurring during hemodialysis treatment by supplemental oxygen.

A patient with end-stage renal disease experienced severe headaches exclusively during dialysis that were bilateral and throbbing with photophobia, weakness, and lightheadedness. The patient had no history of headaches, and dialysis was determined to be the cause of the severe headaches. More than 10 treatments were attempted without success. Headaches were successfully treated and prevented by addition of 100% oxygen (2 L via nasal cannula) for over 12 months without recurrence at time of publication. This case study indicates that oxygen therapy may be a valuable intervention for headaches during dialysis.

Delayed elective total shoulder arthroplasty: causes and eventual outcomes.

PURPOSE: The purpose of this study is to identify risk factors for delays in planned total shoulder arthroplasty (TSA) and determine the perioperative outcomes of TSAs that experienced a delay. METHODS: The American College of Surgeons National Quality Improvement Program (NSQIP) database was queried from 2006 to 2019 for primary TSA. Delayed TSA was defined as surgery that occurred greater than one day after hospital admission. Patient demographics, comorbidities, and post-operative complications were collected and compared; the incidence of delayed TSA was analyzed. RESULTS: The delayed patients were older, had a higher BMI, a higher rate of recent prior major surgery, and more comorbidities. Delayed patients had higher rates of postoperative complications, return to the OR, and 30-day readmission. Between 2006 and 2019, the rate of delayed TSA decreased. CONCLUSION: Surgeons should take care to ensure that patients with comorbidities undergo thorough preoperative clearance to prevent same-day cancellations and postoperative complications.

Discovery of Strong 3-Nitro-2-Phenyl-2H-Chromene Analogues as Antitrypanosomal Agents and Inhibitors of Trypanosoma cruzi Glucokinase.

Chagas disease is one of the world's neglected tropical diseases, caused by the human pathogenic protozoan parasite Trypanosoma cruzi. There is currently a lack of effective and tolerable clinically available therapeutics to treat this life-threatening illness and the discovery of modern alternative options is an urgent matter. T. cruzi glucokinase (TcGlcK) is a potential drug target because its product, d-glucose-6-phosphate, serves as a key metabolite in the pentose phosphate pathway, glycolysis, and gluconeogenesis. In 2019, we identified a novel cluster of TcGlcK inhibitors that also exhibited anti-T. cruzi efficacy called the 3-nitro-2-phenyl-2H-chromene analogues. This was achieved by performing a target-based high-throughput screening (HTS) campaign of 13,040 compounds. The selection criteria were based on first determining which compounds strongly inhibited TcGlcK in a primary screen, followed by establishing on-target confirmed hits from a confirmatory assay. Compounds that exhibited notable in vitro trypanocidal activity over the T. cruzi infective form (trypomastigotes and intracellular amastigotes) co-cultured in NIH-3T3 mammalian host cells, as well as having revealed low NIH-3T3 cytotoxicity, were further considered. Compounds GLK2-003 and GLK2-004 were determined to inhibit TcGlcK quite well with IC50 values of 6.1 µM and 4.8 µM, respectively. Illuminated by these findings, we herein screened a small compound library consisting of thirteen commercially available 3-nitro-2-phenyl-2H-chromene analogues, two of which were GLK2-003 and GLK2-004 (compounds 1 and 9, respectively). Twelve of these compounds had a one-point change from the chemical structure of GLK2-003. The analogues were run through a similar primary screening and confirmatory assay protocol to our previous HTS campaign. Subsequently, three in vitro biological assays were performed where compounds were screened against (a) T. cruzi (Tulahuen strain) infective form co-cultured within NIH-3T3 cells, (b) T. brucei brucei (427 strain) bloodstream form, and (c) NIH-3T3 host cells alone. We report on the TcGlcK inhibitor constant determinations, mode of enzyme inhibition, in vitro antitrypanosomal IC50 determinations, and an assessment of structure-activity relationships. Our results reveal that the 3-nitro-2-phenyl-2H-chromene scaffold holds promise and can be further optimized for both Chagas disease and human African trypanosomiasis early-stage drug discovery research.

Dynamic corticothalamic modulation of the somatosensory thalamocortical circuit during wakefulness.

The feedback projections from cortical layer 6 (L6CT) to the sensory thalamus have long been implicated in playing a primary role in gating sensory signaling but remain poorly understood. To causally elucidate the full range of effects of these projections, we targeted silicon probe recordings to the whisker thalamocortical circuit of awake mice selectively expressing Channelrhodopsin-2 in L6CT neurons. Through optogenetic manipulation of L6CT neurons, multi-site electrophysiological recordings, and modeling of L6CT circuitry, we establish L6CT neurons as dynamic modulators of ongoing spiking in the ventral posteromedial nucleus of the thalamus (VPm), either suppressing or enhancing VPm spiking depending on L6CT neurons' firing rate and synchrony. Differential effects across the cortical excitatory and inhibitory sub-populations point to an overall influence of L6CT feedback on cortical excitability that could have profound implications for regulating sensory signaling across a range of ethologically relevant conditions.

FOXS1 is increased in liver fibrosis and regulates TGFß responsiveness and proliferation pathways in human hepatic stellate cells.

Liver fibrosis commences with liver injury stimulating transforming growth factor beta (TGFß) activation of hepatic stellate cells (HSCs), causing scarring and irreversible damage. TGFß induces expression of the transcription factor Forkhead box S1 (FOXS1) in hepatocytes and may have a role in the pathogenesis of hepatocellular carcinoma (HCC). To date, no studies have determined how it affects HSCs. We analyzed human livers with cirrhosis, HCC, and a murine fibrosis model and found that FOXS1 expression is significantly higher in fibrotic livers but not in HCC. Next, we treated human LX2 HSC cells with TGFß to activate fibrotic pathways, and FOXS1 mRNA was significantly increased. To study TGFß-FOXS1 signaling, we developed human LX2 FOXS1 CRISPR KO and scrambled control HSCs. To determine differentially expressed gene transcripts controlled by TGFß-FOXS1, we performed RNA-seq in the FOXS1 KO and control cells and over 400 gene responses were attenuated in the FOXS1 KO HSCs with TGFß-activation. To validate the RNA-seq findings, we used our state-of-the-art PamGene PamStation kinase activity technology that measures hundreds of signaling pathways nonselectively in real time. Using our RNA-seq data, kinase activity data, and descriptive measurements, we found that FOXS1 controls pathways mediating TGFß responsiveness, protein translation, and proliferation. Our study is the first to identify that FOXS1 may serve as a biomarker for liver fibrosis and HSC activation, which may help with early detection of hepatic fibrosis or treatment options for end-stage liver disease.

A machine learning approach for real-time cortical state estimation.

Objective.Cortical function is under constant modulation by internally-driven, latent variables that regulate excitability, collectively known as 'cortical state'. Despite a vast literature in this area, the estimation of cortical state remains relatively ad hoc, and not amenable to real-time implementation. Here, we implement robust, data-driven, and fast algorithms that address several technical challenges for online cortical state estimation.Approach. We use unsupervised Gaussian mixture models to identify discrete, emergent clusters in spontaneous local field potential signals in cortex. We then extend our approach to a temporally-informed hidden semi-Markov model (HSMM) with Gaussian observations to better model and infer cortical state transitions. Finally, we implement our HSMM cortical state inference algorithms in a real-time system, evaluating their performance in emulation experiments.Main results. Unsupervised clustering approaches reveal emergent state-like structure in spontaneous electrophysiological data that recapitulate arousal-related cortical states as indexed by behavioral indicators. HSMMs enable cortical state inferences in a real-time context by modeling the temporal dynamics of cortical state switching. Using HSMMs provides robustness to state estimates arising from noisy, sequential electrophysiological data.Significance. To our knowledge, this work represents the first implementation of a real-time software tool for continuously decoding cortical states with high temporal resolution (40 ms). The software tools that we provide can facilitate our understanding of how cortical states dynamically modulate cortical function on a moment-by-moment basis and provide a basis for state-aware brain machine interfaces across health and disease.

Dynamic corticothalamic modulation of the somatosensory thalamocortical circuit during wakefulness.

The feedback projections from cortical layer 6 (L6CT) to sensory thalamus have long been implicated in playing a primary role in gating sensory signaling but remain poorly understood. To causally elucidate the full range of effects of these projections, we targeted silicon probe recordings to the whisker thalamocortical circuit of awake mice selectively expressing Channelrhodopsin-2 in L6CT neurons. Through optogenetic manipulation of L6CT neurons, multi-site electrophysiological recordings, and modeling of L6CT circuitry, we establish L6CT neurons as dynamic modulators of ongoing spiking in the ventro-posterior-medial nucleus of thalamus (VPm), either suppressing or enhancing VPm spiking depending on L6CT neurons' firing rate and synchrony. Differential effects across the cortical excitatory and inhibitory sub-populations point to an overall influence of L6CT feedback on cortical excitability that could have profound implications for regulating sensory signaling across a range of ethologically relevant conditions.

Engaging early experiential learners to improve quality at a VA medical center - a cross-sectional analysis.

PURPOSE: An innovative population health-based introductory pharmacy practice experience (IPPE) leveraging a Veterans Affairs (VA) and college of pharmacy collaboration was implemented in fall 2019. All second-year pharmacy students from the college actively engage in the evaluation of the medical records of veterans identified using population health management tools as needing additional care or experiencing a gap in care. This study examines the clinical impact of the experience on the care of patients at the partnering VA medical center. METHODS: Course and patient records were reviewed to enumerate the number and types of interventions performed as part of the IPPE from fall 2019 to spring 2021. Descriptive statistics were used to report clinical impact. Where relevant, t test analysis was used to compare pre- and postintervention clinical values. RESULTS: A total of 1,794 medical records were reviewed. An average of 2.67 interventions were completed for each of the 615 veterans receiving an intervention. A total of 155 patients were identified as needing routine laboratory tests (eg, glycated hemoglobin), with 48.4% of patients receiving recommended laboratory tests within 3 months. Thirty-three veterans were eligible for prescription renewals, resulting in 43 medication orders. Thirty-six veterans were recommended to take a statin medication, and statin therapy was initiated in 11, resulting in a significant decrease in the mean (SD) low-density lipoprotein cholesterol concentration (-42.4 [30.3] mg/dL, P < 0.05). Eight hundred immunizations were recommended for 632 veterans, and 286 recommendations were verbally accepted. CONCLUSION: This study demonstrates that a population health-based IPPE can provide significant clinical support to the care of patients within the VA health system.

Nebulized medications in the emergency department: A narrative review of nontraditional agents.

PURPOSE: This article summarizes emerging nontraditional therapies administered via the nebulization route for use in the emergency department (ED). SUMMARY: Although traditional routes of medication administration (eg, intravenous) have been the mainstay of administration modalities for decades, these routes may not be appropriate for all patients. Nowhere is this more readily apparent than in the ED setting, where patients with a variety of presentations receive care. One unique route for medication administration that has increasingly gained popularity in the ED is that of aerosolized drug delivery. This route holds promise as direct delivery of medications to the site of action could yield a more rapid and effective therapeutic response while also minimizing systemic adverse effects by utilizing a fraction of the systemic dose. Medication administration via nebulization also provides an alternative that is conducive to rapid, less invasive access, which is advantageous in the emergent setting of the ED. This review is intended to analyze the existing literature regarding this route of administration, including the nuances that can impact drug efficacy, as well as the available literature regarding novel, noncommercial nebulized medication therapy given in the ED. CONCLUSION: Multiple medications have been investigated for administration via this route, and when implementing any of these therapies several practical considerations must be taken into account, from medication preparation to administration, to ensure optimal efficacy while minimizing adverse effects. The pharmacist is an essential bedside team member in these scenarios to assist with navigating unique and complex nuances of this therapy as they develop.

Evaluation of Sugammadex Dosing for Neurological Examination in the Emergency Department.

BACKGROUND: Prolong effects of non-depolarizing neuromuscular blocking agents after rapid sequence intubation may prevent meaningful neurological examination, delaying appropriate diagnosis and neurosurgical intervention. Sugammadex is indicated for the reversal of neuromuscular blockade induced by rocuronium. OBJECTIVE: The objective of this study was to evaluate low- (2 mg/kg) vs standard-dose (4 mg/kg) sugammadex for rocuronium-induced deep neuromuscular blockade reversal in the emergency department (ED) by achieving a post-treatment train-of-four (TOF) of 4 to facilitate neurological examination. METHODS: This was a single-center, retrospective, cohort study evaluating low-vs standard-dose sugammadex for neuromuscular blockade reversal in the ED. RESULTS: 34 patients were identified within the designated time period, 24 of which were included in the final analysis ([n = 9 low-dose], [n = 15 standard-dose]). Median sugammadex doses were 2.3 mg/kg and 4.1 mg/kg for low- and standard-dose, respectively. The majority of patients presented for intraparenchymal hemorrhage (54.2%). No significant difference in success rate of NMBA reversal was found between low- and standard-dose sugammadex ([100.0% vs 93.3%], P = 1.000). A total of 9 patients had a neurosurgical procedure performed after sugammadex administration. Low-dose sugammadex was associated with significantly less acquisition cost compared to the standard dose (P < .001). CONCLUSION: Low- (2 mg/kg) and standard-dose (4 mg/kg) sugammadex successfully reversed rocuronium-induced deep neuromuscular blockade in the ED by achieving a post-treatment TOF of 4 to facilitate neurologic examination. Low-dose sugammadex may be a viable option for deep NMBA reversal in the ED and is associated with decreased institutional cost.

Soft Tissue Pathology.

A wide spectrum of pathologies can lead to soft tissue abnormalities within the ankle joint. Many of these disorders can develop into irreversible joint degeneration if left untreated. Arthroscopy is frequently used to treat these soft tissue conditions such as instability, synovitis, impingement, arthrofibrosis, and other inflammatory disorders in the rearfoot and ankle. In general, the etiology of these ankle soft tissue disorders can be classified as traumatic, inflammatory, and congenital/neoplastic. Overall, the goal of diagnosing and treating soft tissue pathologies of the ankle is to restore anatomic and physiologic motion, reduce pain, optimize functional return to activity, and decrease the chance of recurrence while minimizing complications.

Rocuronium Reversal in the Emergency Department: Retrospective Evaluation of Hemodynamic Instability Following Administration of Sugammadex Versus Neostigmine With Glycopyrrolate.

Background: Rocuronium is an intermediate-acting non-depolarizing neuromuscular blocking agent frequently used in the emergency department for rapid sequence intubation. The prolonged effects of rocuronium may prevent the ability to conduct a meaningful neurological examination, thereby delaying appropriate diagnosis and treatment. Sugammadex and neostigmine are pharmacologic agents commonly used to reverse rocuronium. The safety of sugammadex versus neostigmine with glycopyrrolate for the reversal of rocuronium in the emergency department has not been well described. Objective: Evaluate the occurrence of hemodynamic instability post-administration of sugammadex versus neostigmine with glycopyrrolate in the emergency department for the reversal of rocuronium. Methods: A retrospective cohort study conducted among adult patients that received sugammadex or neostigmine with glycopyrrolate in the emergency department for the reversal of rocuronium. The primary outcome was occurrence of hemodynamic instability that required escalation of treatment. Secondary outcomes included occurrence of hypotensive, bradycardic, or cardiac arrest events. Results: A total of 37 patients met inclusion criteria (n = 10, sugammadex; n = 27, neostigmine). There was no difference between the two groups in regard to hemodynamic instability that required escalation of treatment within 30 minutes after receiving either sugammadex or neostigmine with glycopyrrolate (P = .557). Conclusion: There was no difference between the two groups in regard to occurrence of hemodynamic instability that required escalation of treatment. Given the small sample size, future studies are warranted to further delineate the safety of sugammadex and neostigmine with glycopyrrolate for the reversal of rocuronium in the emergency department.

Estrogens rapidly shape synaptic and intrinsic properties to regulate the temporal precision of songbird auditory neurons.

Sensory neurons parse millisecond-variant sound streams like birdsong and speech with exquisite precision. The auditory pallial cortex of vocal learners like humans and songbirds contains an unconventional neuromodulatory system: neuronal expression of the estrogen synthesis enzyme aromatase. Local forebrain neuroestrogens fluctuate when songbirds hear a song, and subsequently modulate bursting, gain, and temporal coding properties of auditory neurons. However, the way neuroestrogens shape intrinsic and synaptic properties of sensory neurons remains unknown. Here, using a combination of whole-cell patch clamp electrophysiology and calcium imaging, we investigate estrogenic neuromodulation of auditory neurons in a region resembling mammalian auditory association cortex. We found that estradiol rapidly enhances the temporal precision of neuronal firing via a membrane-bound G-protein coupled receptor and that estradiol rapidly suppresses inhibitory synaptic currents while sparing excitation. Notably, the rapid suppression of intrinsic excitability by estradiol was predicted by membrane input resistance and was observed in both males and females. These findings were corroborated by analysis of in vivo electrophysiology recordings, in which local estrogen synthesis blockade caused acute disruption of the temporal correlation of song-evoked firing patterns. Therefore, on a modulatory timescale, neuroestrogens alter intrinsic cellular properties and inhibitory neurotransmitter release to regulate the temporal precision of higher-order sensory neurons.

Comparison of Reverse and Anatomic Total Shoulder Arthroplasty in Patients With an Intact Rotator Cuff and No Previous Surgery.

INTRODUCTION: This study's purpose is to compare clinical and radiographic outcomes of primary anatomic total shoulder arthroplasty (aTSA) and primary reverse total shoulder arthroplasty (rTSA) patients with osteoarthritis (OA) and an intact rotator cuff with no previous history of shoulder surgery using a single platform TSA system at a minimum follow-up of 2 years. METHODS: A total of 370 aTSA patients and 370 rTSA patients matched for age, sex, and length of follow-up from an international multi-institutional Western Institutional Review Board approved registry with a minimum 2-year follow-up were reviewed for this study. All patients had a diagnosis of OA, an intact rotator cuff, and no previous shoulder surgery. All patients were evaluated and scored preoperatively and at latest follow-up using six outcome scoring metrics and four active range of motion measurements. RESULTS: Mean follow-up was 41 months, and the mean age was 73 years. Preoperatively, the rTSA patients had lower outcome metrics and less motion. Postoperatively, aTSA and rTSA patients had similar clinical outcomes, motion, and function, with the only exception being greater external rotation in aTSA exceeding the minimal clinically important difference. Pain relief was excellent, and patient satisfaction was high in both groups. Humeral radiolucent lines were similar in both groups (8%). Complications were significantly higher with aTSA (aTSA = 4.9%; rTSA = 2.2%; P = 0.045), but revisions were similar (aTSA = 3.2%; rTSA = 1.4%; P = 0.086). CONCLUSION: At a mean of 41 month follow-up, primary aTSA and rTSA patients with OA and an intact rotator cuff with no previous history of shoulder surgery had similar clinical and radiographic outcomes. Greater external rotation was noted in aTSA patients at follow-up. However, aTSA patients had a significantly greater rate of complications compared with rTSA patients. rTSA is a viable treatment option in patients with an intact rotator cuff and no previous shoulder surgery, offering similar clinical outcomes with a lower complication rate. LEVEL OF EVIDENCE: Level III.