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Though much is known about the cellular and molecular components of the circadian clock, output pathways that couple clock cells to overt behaviors have not been identified. We conducted a screen for circadian-relevant neurons in the Drosophila brain and report here that cells of the pars intercerebralis (PI), a functional homolog of the mammalian hypothalamus, comprise an important component of the circadian output pathway for rest:activity rhythms. GFP reconstitution across synaptic partners (GRASP) analysis demonstrates that PI cells are connected to the clock through a polysynaptic circuit extending from pacemaker cells to PI neurons. Molecular profiling of relevant PI cells identified the corticotropin-releasing factor (CRF) homolog, DH44, as a circadian output molecule that is specifically expressed by PI neurons and is required for normal rest:activity rhythms. Notably, selective activation or ablation of just six DH44+ PI cells causes arrhythmicity. These findings delineate a circuit through which clock cells can modulate locomotor rhythms.
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Relojes Circadianos , Drosophila/fisiología , Neuronas/fisiología , Animales , Animales Modificados Genéticamente , Encéfalo/citología , Encéfalo/fisiología , Ritmo Circadiano , Drosophila/citología , Neuronas/citología , Análisis de la Célula Individual , TranscriptomaRESUMEN
BACKGROUND: Spinal surgeries are being offered to a broader patient population who are both medically and surgically complex. History of prior spinal surgery, advanced age, and presence of comorbidities, such as obesity, malnutrition, steroid use, and tobacco use, are risk factors for postoperative complications. Prophylactic spinal reconstruction at the time of spinal surgery has been shown to have improved outcomes and decreased wound complications; however, outcomes focusing specifically on complex patients with a history of previous spinal surgery (or surgeries) have not been well described. METHODS: This is a retrospective study performed at the University of Maryland Medical Center (Baltimore, MD) of high-risk patients who underwent complex spinal surgery with prophylactic spinal reconstruction from 2011 to 2022. One hundred forty-three consecutive surgeries from 136 patients were included in the study. Patients younger than 17 years or who had an incomplete medical record were excluded. RESULTS: Most patients were female (63.6%) versus male (31.5%). The average American Society of Anesthesiologists score was 3. All but 6 patients (11%) had a history of at least 1 spinal surgery, with nearly half of patients having had between 2 and 5 spinal surgeries. Reconstruction was performed with paraspinous flaps in most cases (n = 133 [93%]). The overall complication rate was 10.5%, with surgical site infection being the most common complication. Seventeen patients (12.5%) underwent reoperation within 90 days of initial surgery. Average length of follow-up was 4.18 months (range, 0.03-40.53 months). CONCLUSIONS: In appropriately selected patients, prophylactic spinal reconstruction offers improved outcomes with decreased wound complications compared with salvage. For large defects, paraspinous flaps are recommended over other reconstructive options. Prolonged drain placement is felt to be protective against complications.
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STUDY DESIGN: Retrospective Case Series. OBJECTIVES: This study aims to determine complications, readmission, and revision surgery rates in patients undergoing single position surgery (SPS) for surgical treatment of traumatic and pathologic thoracolumbar fractures. METHODS: A multi-center review of patients who underwent SPS in the lateral decubitus position (LSPS) for surgical management of traumatic or pathologic thoracolumbar fractures between January 2016 and May 2020 was conducted. Operative time, estimated blood loss (EBL), intraoperative complications, postoperative complications, readmissions, and revision surgeries were collected. RESULTS: A total of 12 patients with a mean age of 45 years (66.67% male) were included. The majority of patients underwent operative treatment for acute thoracolumbar trauma (66.67%) with a mean injury severity score (ISS) of 16.71. Mean operative time was 175.5 min, mean EBL of 816.67 cc. Five patients experienced a complication, two of which required revision surgery for additional decompression during the initial admission. All ambulatory patients were mobilized on postoperative day 1. The mean hospital length of stay (LOS) was 9.67 days. CONCLUSION: The results of this case series supports LSPS as a feasible alternative to the traditional combined anterior-posterior approach for surgical treatment of pathologic and thoracolumbar fractures. These results are similar to reductions in operative time, EBL, and LOS seen in the elective spine literature with LSPS. LEVEL OF EVIDENCE: IV.
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Fracturas de la Columna Vertebral , Descompresión Quirúrgica/métodos , Femenino , Fijación Interna de Fracturas/métodos , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/lesiones , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/patología , Fracturas de la Columna Vertebral/cirugía , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/lesiones , Vértebras Torácicas/cirugía , Resultado del TratamientoRESUMEN
PURPOSE: Expansion of the anterior column and compression of the posterior column restores lordosis and sagittal imbalance. Anterior longitudinal ligament (ALL) release has been described from lateral and anterior approaches as a technique to improve lumbar lordosis; however, posterior approach to release the ALL has not been adequately assessed. METHODS: We demonstrate a case series of ALL release using a posterior approach performed in conjunction with posterior column osteotomy (PCO), with or without transforaminal lumbar interbody fusion (TLIF) for spinal deformity. Eleven cases were identified from billing records between 2010 and 2019. Retrospective review was conducted for perioperative complications and revision surgery. Overall and segmental lumbar lordosis (LL) correction was measured from pre- and postoperative imaging. RESULTS: Eleven patients underwent ALL release with a PCO. Kyphosis, scoliosis, and flat back syndrome were the most common spinal deformities. On average, patients had 9 ± 3 levels fused and a single level ALL release. ALL release was most commonly performed at L1-L2 and L2-L3 levels. An overall LL correction of 28.6° ± 19.8o was achieved; ALL release introduced 16.7° ± 11.9° of lordotic correction and accounted for 49.2 ± 30.4% of the overall lordotic correction. Average blood loss was 1030 ± 573 mL. CONCLUSIONS: ALL release as an adjunct to PCO and TLIF is a viable technique for providing increased deformity correction without subjecting the patient to a more invasive three-column osteotomy. While this approach may not be appropriate for all patients, it represents a useful option in spinal deformity correction while limiting blood loss and additional anterior surgery. LEVEL OF EVIDENCE: IV.
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Lordosis , Fusión Vertebral , Humanos , Ligamentos Longitudinales/diagnóstico por imagen , Ligamentos Longitudinales/cirugía , Lordosis/cirugía , Vértebras Lumbares/anomalías , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Osteotomía/métodos , Estudios Retrospectivos , Fusión Vertebral/métodos , Resultado del TratamientoRESUMEN
Circadian rhythms allow animals to coordinate behavioral and physiological processes with respect to one another and to synchronize these processes to external environmental cycles. In most animals, circadian rhythms are produced by core clock neurons in the brain that generate and transmit time-of-day signals to downstream tissues, driving overt rhythms. The neuronal pathways controlling clock outputs, however, are not well understood. Furthermore, it is unclear how the central clock modulates multiple distinct circadian outputs. Identifying the cellular components and neuronal circuitry underlying circadian regulation is increasingly recognized as a critical step in the effort to address health pathologies linked to circadian disruption, including heart disease and metabolic disorders. Here, building on the conserved components of circadian and metabolic systems in mammals and Drosophila melanogaster, we used a recently developed feeding monitor to characterize the contribution to circadian feeding rhythms of two key neuronal populations in the Drosophila pars intercerebralis (PI), which is functionally homologous to the mammalian hypothalamus. We demonstrate that thermogenetic manipulations of PI neurons expressing the neuropeptide SIFamide (SIFa) as well as mutations of the SIFa gene degrade feeding:fasting rhythms. In contrast, manipulations of a nearby population of PI neurons that express the Drosophila insulin-like peptides (DILPs) affect total food consumption but leave feeding rhythms intact. The distinct contribution of these two PI cell populations to feeding is accompanied by vastly different neuronal connectivity as determined by trans-Tango synaptic mapping. These results for the first time identify a non-clock cell neuronal population in Drosophila that regulates feeding rhythms and furthermore demonstrate dissociable control of circadian and homeostatic aspects of feeding regulation by molecularly-defined neurons in a putative circadian output hub.
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Relojes Circadianos/genética , Drosophila melanogaster/genética , Conducta Alimentaria/fisiología , Proteínas Circadianas Period/genética , Animales , Animales Modificados Genéticamente , Encéfalo/fisiología , Ritmo Circadiano/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/fisiología , Ayuno , Hipotálamo/metabolismo , Mamíferos/genética , Mamíferos/fisiología , Neuroglía/fisiología , Neuronas/metabolismo , Neuropéptidos/genética , Neuropéptidos/metabolismoRESUMEN
BACKGROUND: Circadian clocks are found in nearly all organisms, from bacteria to mammals, and ensure that behavioral and physiological processes occur at optimal times of day and in the correct temporal order. It is becoming increasingly clear that chronic circadian misalignment (CCM), such as occurs in shift workers or as a result of aberrant sleeping and eating schedules common to modern society, has profound metabolic and cognitive consequences, but the proximate mechanisms connecting CCM with reduced organismal health are unknown. Furthermore, it has been difficult to disentangle whether the health effects are directly induced by misalignment or are secondary to the alterations in sleep and activity levels that commonly occur with CCM. Here, we investigated the consequences of CCM in the powerful model system of the fruit fly, Drosophila melanogaster. We subjected flies to daily 4-h phase delays in the light-dark schedule and used the Drosophila Activity Monitoring (DAM) system to continuously track locomotor activity and sleep while simultaneously monitoring fly lifespan. RESULTS: Consistent with previous results, we find that exposing flies to CCM leads to a ~ 15% reduction in median lifespan in both male and female flies. Importantly, we demonstrate that the reduced longevity occurs independent of changes in overall sleep or activity. To uncover potential molecular mechanisms of CCM-induced reduction in lifespan, we conducted whole body RNA-sequencing to assess differences in gene transcription between control and misaligned flies. CCM caused progressive, large-scale changes in gene expression characterized by upregulation of genes involved in response to toxic substances, aging and oxidative stress, and downregulation of genes involved in regulation of development and differentiation, gene expression and biosynthesis. CONCLUSIONS: Many of these gene expression changes mimic those that occur during natural aging, consistent with the idea that CCM results in premature organismal decline, however, we found that genes involved in lipid metabolism are overrepresented among those that are differentially regulated by CCM and aging. This category of genes is also among the earliest to exhibit CCM-induced changes in expression, thus highlighting altered lipid metabolism as a potentially important mediator of the negative health consequences of CCM.
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Relojes Circadianos/genética , Ritmo Circadiano/genética , Longevidad/genética , Trastornos del Sueño del Ritmo Circadiano/genética , Animales , Relojes Circadianos/fisiología , Ritmo Circadiano/fisiología , Drosophila melanogaster/genética , Drosophila melanogaster/fisiología , Conducta Alimentaria/fisiología , Femenino , Locomoción/genética , Longevidad/fisiología , Masculino , Estrés Oxidativo , Horario de Trabajo por Turnos , Trastornos del Sueño del Ritmo Circadiano/fisiopatologíaRESUMEN
The circadian system coordinates multiple behavioral outputs to ensure proper temporal organization. Timing information underlying circadian regulation of behavior depends on a molecular circadian clock that operates within clock neurons in the brain. In Drosophila and other organisms, clock neurons can be divided into several molecularly and functionally discrete subpopulations that form an interconnected central clock network. It is unknown how circadian signals are coherently generated by the clock network and transmitted across output circuits that connect clock cells to downstream neurons that regulate behavior. Here, we have exhaustively investigated the contribution of clock neuron subsets to the control of two prominent behavioral outputs in Drosophila: locomotor activity and feeding. We have used cell-specific manipulations to eliminate molecular clock function or induce electrical silencing either broadly throughout the clock network or in specific subpopulations. We find that clock cell manipulations produce similar changes in locomotor activity and feeding, suggesting that overlapping central clock circuitry regulates these distinct behavioral outputs. Interestingly, the magnitude and nature of the effects depend on the clock subset targeted. Lateral clock neuron manipulations profoundly degrade the rhythmicity of feeding and activity. In contrast, dorsal clock neuron manipulations only subtly affect rhythmicity but produce pronounced changes in the distribution of activity and feeding across the day. These experiments expand our knowledge of clock regulation of activity rhythms and offer the first extensive characterization of central clock control of feeding rhythms. Despite similar effects of central clock cell disruptions on activity and feeding, we find that manipulations that prevent functional signaling in an identified output circuit preferentially degrade locomotor activity rhythms, leaving feeding rhythms relatively intact. This demonstrates that activity and feeding are indeed dissociable behaviors, and furthermore suggests that differential circadian control of these behaviors diverges in output circuits downstream of the clock network.
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Thoracic myelopathy can be a challenging condition to diagnose and treat. Successful outcomes depend on early recondition of the pathology and appropriate surgical referral in cases of progressive neurologic deterioration. The thoracic cord is tethered in kyphosis by the dentate ligaments and contains a tenuous blood supply. These conditions make the thoracic cord particularly susceptible to external compression and ischemic damage. Careful preoperative planning with specific attention to the location and source of thoracic stenosis is critical to successful decompression and complication avoidance. The purpose of this discussion is to outline the common sources of thoracic myelopathy and current recommendations regarding diagnosis and management. The review concludes with an overview of the most up-to-date literature regarding clinical outcomes.
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BACKGROUND CONTEXT: Traumatic spinal injuries (TSI) are associated with high morbidity, mortality, and resource utilization. The epidemiology of TSI varies greatly across different countries and regions and is impacted by national income levels, infrastructure, and cultural factors. Further, there may be changes over time. It is essential to investigate TSI to gain useful epidemiologic information. However, there have been no recent studies on trends for TSI in the US, despite the changing population demographics, healthcare policy, and technology. As a result, reexamination is warranted to reflect how the modern era has affected the epidemiology of US spine trauma patients and their management. PURPOSE: To determine epidemiologic trends in traumatic spine injuries over time. STUDY DESIGN/SETTING: Retrospective analysis; level 1 trauma center in the United States. PATIENT SAMPLE: A total of 21,811 patients, between the years of 1996 and 2022, who presented with traumatic spine injury. OUTCOME MEASURES: Age, sex, race, Injury Severity Score, mechanism of injury, injury diagnosis, injury level, rate of operative intervention, hospital length of stay, intensive care unit length of stay, discharge disposition, in-hospital mortality. METHODS: Data was collected from our institutional trauma registry over a 26-year period. Inclusion criteria involved at least one diagnosis of vertebral fracture, spinal cord injury, spinal subluxation, or intervertebral disc injury. Exclusion criteria consisted of patients with no diagnosed spine injury or a diagnosis of strain only. A total of 21,811 patients were included in the analysis. Descriptive statistics were tabulated and ordinary least squares linear regression was conducted for trends analysis. RESULTS: Regression analysis showed a significant upward trend in patient age (+13.83 years, ß=+0.65/year, p<.001), female sex (+2.7%, ß=+0.18%/year, p=.004), falls (+10.5%, ß=+0.82%/year, p<.001), subluxations (+12.8%, ß=+0.35%/year, p<.001), thoracic injuries (+1.5%, ß=+0.28%/year, p<.001), and discharges to subacute rehab (+15.9%, ß=+0.68%/year, p<.001). There was a significant downward trend in motor vehicle crashes (-7.8%, ß=-0.47%/year, p=.016), firearms injuries (-3.4%, ß=-0.19%/year, p<.001), sports/recreation injuries (-2.9%, ß=-0.18%/year, p<.001), spinal cord injuries (-11.25%, ß=-0.37%, p<.001), complete spinal cord injuries (-7.6%, ß=-0.24%/year, p<.001), and discharges to home (+4.5%, ß=-0.27%/year, p=.011). CONCLUSIONS: At our institution, the average spine trauma patient has trended toward older females. Falls represent an increasing proportion of the mechanism of injury, on a trajectory to become the most common cause. With time, there have been fewer spinal cord injuries and a lower proportion of complete injuries. At discharge, there has been a surge in the utilization of subacute rehabilitation facilities. Overall, there has been no significant change in injury severity, rate of operative intervention, length of stay, or mortality.
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Traumatismos Vertebrales , Centros Traumatológicos , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Centros Traumatológicos/estadística & datos numéricos , Traumatismos Vertebrales/epidemiología , Estados Unidos/epidemiología , Estudios Retrospectivos , Anciano , Adolescente , Tiempo de Internación/estadística & datos numéricos , Adulto Joven , Niño , Puntaje de Gravedad del TraumatismoRESUMEN
Background/Objectives: A superinfection occurs when a new, secondary organism colonizes an existing infection. Spine infections are associated with high patient morbidity and sometimes require multiple irrigations and debridements (I&Ds). When multiple I&Ds are required, the risk of complications increases. The purpose of this study was to report our experience with spine superinfections and determine which patients are typically affected. Methods: A retrospective case series of spine superinfections and a retrospective case-control analysis were conducted. Data were collected manually from electronic medical records. Spine I&Ds were identified. Groups were created for patients who had multiple I&Ds for (1) a recurrence of the same causative organism or (2) a superinfection with a novel organism. Preoperative demographic, clinical, and microbiologic data were compared between these two outcomes. A case series of superinfections with descriptive data was constructed. Lastly, two illustrative cases were provided in a narrative format. Results: A total of 92 patients were included in this analysis. Superinfections occurred after 6 out of the 92 (7%) initial I&Ds and were responsible for 6 out of the 24 (25%) repeat I&Ds. The preoperative erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) of the patients with a superinfection were significantly lower than those in the control group (p = 0.022 and p = 0.032). Otherwise, the observed differences in the preoperative variables were not statistically different. In the six cases of superinfection, the presence of high-risk comorbidities, a history of substance abuse, or a lack of social support were commonly observed. The superinfecting organisms included Candida, Pseudomonas, Serratia, Klebsiella, Enterobacter, and Staphylococcus species. Conclusions: Superinfections are a devastating complication requiring reoperation after initial spine I&D. Awareness of the possibility of superinfection and common patient archetypes can be helpful for clinicians and care teams. Future work is needed to examine how to identify, help predict, and prevent spine superinfections.
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BACKGROUND: Traumatic cervical spinal cord injury (tCSCI) is often a debilitating injury, making early prognosis important for medical and surgical planning. Currently, the best early predictors of prognosis are physical examination, imaging studies, and patient demographics. Despite these factors, patient outcomes continue to vary significantly. The purpose of this study was to evaluate the prognostic value of somatosensory evoked potentials (SSEPs) with functional outcomes in tCSCI patients. METHODS: A retrospective study was conducted on prospectively collected data from 2 academic institutions. Patients 18 years and older who had tCSCI and underwent posterior cervical decompression and stabilization with intraoperative neuromonitoring were reviewed. The outcomes of interest were the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade and ASIA motor score at follow-up. Outcomes measures were assessed via student t-tests, chi-squared tests, and multivariable regression analysis. RESULTS: A total of 79 patients were included. In complete injuries, detectable lower extremity SSEPs were associated with higher ASIA motor scores at follow-up (P = 0.002), greater increases in ASIA motor scores at follow-up (P = 0.009), and a greater likelihood of clinically important improvement in ASIA motor score (P = 0.024). Incomplete, AIS grade C injuries has higher rates of grade conversion (P = 0.019) and clinically important improvement in ASIA motor score (P = 0.010), compared to AIS grade A or B injuries. CONCLUSIONS: The detection of lower extremity SSEP signals during initial surgical treatment of tCSCI is associated with greater improvement in ASIA motor scores postoperatively. The association is most applicable to patients with complete injury.
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Médula Cervical , Traumatismos del Cuello , Traumatismos de los Tejidos Blandos , Traumatismos de la Médula Espinal , Traumatismos Vertebrales , Humanos , Médula Cervical/lesiones , Estudios Retrospectivos , Potenciales Evocados Somatosensoriales , Extremidad InferiorRESUMEN
OBJECTIVE: To compare the 2-year reoperation rates for adjacent segment disease between patients with pelvic incidence-lumbar lordosis (PI-LL) mismatch postoperatively and patients with normal PI-LL measurements. METHODS: Patients undergoing elective 1- to 2-level lumbar fusion for degenerative conditions between 2016 and 2018 were retrospectively reviewed. Spinopelvic radiographic parameters immediately postoperation were measured, and PI-LL mismatch was determined using the age-adjusted thresholds defined in Lafage et al. After propensity score matching, early reoperation rates were compared between the PI-LL mismatch and normal PI-LL cohorts. Early reoperation was defined as symptomatic adjacent segment disease (ASD) requiring reoperation within 2 years of the index surgery. RESULTS: A total of 219 patients were identified. The average age was 59 years of age, with 59.8% female. The PI-LL mismatch cohort (n = 148) was younger (57.5 vs. 63.5 years, P < 0.001) and had a higher proportion of Black patients (31.8% vs. 11.3%, P = 0.001) than the normal PI-LL cohort, respectively. A total of 100 patients in the PI-LL mismatch cohort were propensity score matched to 66 patients in the normal PI-LL cohort, resulting in no difference in age (P = 0.177), sex (P = 0.302), race (P = 0.727), or body mass index (P = 0.892). Using these matched cohorts, the rate of early reoperation for ASD was 8.0% in the PI-LL mismatch cohort and 9.1% in the normal PI-LL cohort (P = 0.805), with a mean time to reoperation of 1.28 and 1.33 years, respectively. CONCLUSIONS: After propensity score matching, PI-LL mismatch was not associated with early reoperation for ASD in patients undergoing 1- to 2-level lumbar fusions for degenerative conditions.
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STUDY DESIGN: Prospective, single-center study. OBJECTIVE: To evaluate the clinical relevance of the validated intraoperative bleeding severity scale (VIBe) in thoracolumbar spine surgery. METHODS: Adult patients aged 18 through 88 undergoing elective decompression, instrumentation, and fusion of the thoracolumbar spine were prospectively enrolled after informed consent was provided and written consent was obtained. Validated intraoperative bleeding severity scores were recorded intraoperatively. Univariate analysis consisted of Student T-tests, Pearson's χ2 Tests, Fisher's Exact Tests, linear regression, and binary logistic regression. Multivariable regression was conducted to adjust for baseline characteristics and potential confounding variables. RESULTS: A total of N = 121 patients were enrolled and included in the analysis. After adjusting for confounders, VIBe scores were correlated with an increased likelihood of intraoperative blood transfusion (ß = 2.46, P = .012), postoperative blood transfusion (ß = 2.36, P = .015), any transfusion (ß = 2.49, P < .001), total transfusion volume (ß = 180.8, P = .020), and estimated blood loss (EBL) (ß = 409, P < .001). Validated intraoperative bleeding severity scores had no significant association with length of hospital stay, 30-day readmission, 30-day reoperation, 30-day emergency department visit, change in pre- to post-op hemoglobin and hematocrit, total drain output, or length of surgery. CONCLUSION: The VIBe scale is associated with perioperative transfusion rates and EBL in patients undergoing thoracolumbar spine surgery. Overall, the VIBe scale has clinically relevant meaning in spine surgery, and shows potential utility in clinical research. LEVEL OF EVIDENCE: Level II.
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We previously demonstrated that genetic and/or pharmacological ablation of the TRPV1+/peptidergic or the MrgprD+/non-peptidergic subset of nociceptors produced selective, modality-specific deficits in the behavioural responses to heat and mechanical stimuli, respectively. To assess whether this modality-specific contribution is also manifest at the level of spinal cord neuron responsiveness, here we made extracellular recordings from lumbar dorsal horn neurons of the mouse in response to graded thermal and mechanical stimulation. We found that, following intrathecal injection of capsaicin to eliminate the central terminals of TRPV1+ nociceptors, neurons in the region of laminae I and V of the spinal cord lost responsiveness to noxious heat (whether generated by a contact heat probe or diode laser), with no change in their response to noxious mechanical stimulation. In contrast, ablation of MrgprD+ afferents did not alter the response to noxious heat, but reduced the firing of superficial dorsal horn nociceptive-specific neurons in response to graded mechanical stimulation and decreased the relative number of wide dynamic range neurons that were exclusively mechanosensitive. Neither ablation procedure reduced the number of dorsal horn neurons that responded to noxious cold. These findings support the conclusion that TRPV1+ nociceptors are necessary and probably sufficient for noxious heat activation of dorsal horn neurons and that, despite their polymodal properties, TRPV1+ and MrgprD+ nociceptors provide modality-specific contributions to the response properties of spinal cord neurons.
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Nociceptores/fisiología , Células del Asta Posterior/fisiología , Receptores Acoplados a Proteínas G/fisiología , Canales Catiónicos TRPV/fisiología , Animales , Calor , Ratones , Ratones Endogámicos C57BL , Péptidos , Estimulación FísicaRESUMEN
Organisms track time of day through the function of cell-autonomous molecular clocks. In addition to a central clock located in the brain, molecular clocks are present in most peripheral tissues. Circadian clocks are coordinated within and across tissues, but the manner through which this coordination is achieved is not well understood. We reasoned that the ability to track in vivo molecular clock activity in specific tissues of the fruit fly, Drosophila melanogaster, would facilitate an investigation into the relationship between different clock-containing tissues. Previous efforts to monitor clock gene expression in single flies in vivo have used regulatory elements of several different clock genes to dictate expression of a luciferase reporter enzyme, the activity of which can be monitored using a luminometer. Although these reporter lines have been instrumental in our understanding of the circadian system, they generally lack cell specificity, making it difficult to compare molecular clock oscillations between different tissues. Here, we report the generation of several novel lines of flies that allow for inducible expression of a luciferase reporter construct for clock gene transcriptional activity. We find that these lines faithfully report circadian transcription, as they exhibit rhythmic luciferase activity that is dependent on a functional molecular clock. Furthermore, we take advantage of our reporter lines' tissue specificity to demonstrate that peripheral molecular clocks are able to retain rhythmicity for multiple days under constant environmental conditions.
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Relojes Circadianos , Proteínas de Drosophila , Animales , Relojes Circadianos/genética , Drosophila , Drosophila melanogaster/genética , Ritmo Circadiano/genética , Proteínas de Drosophila/genética , Luciferasas/genéticaRESUMEN
In adulthood, sleep-wake rhythms are one of the most prominent behaviors under circadian control. However, during early life, sleep is spread across the 24-hour day. The mechanism through which sleep rhythms emerge, and consequent advantage conferred to a juvenile animal, is unknown. In the second-instar Drosophila larvae (L2), like in human infants, sleep is not under circadian control. We identify the precise developmental time point when the clock begins to regulate sleep in Drosophila, leading to emergence of sleep rhythms in early third-instars (L3). At this stage, a cellular connection forms between DN1a clock neurons and arousal-promoting Dh44 neurons, bringing arousal under clock control to drive emergence of circadian sleep. Last, we demonstrate that L3 but not L2 larvae exhibit long-term memory (LTM) of aversive cues and that this LTM depends upon deep sleep generated once sleep rhythms begin. We propose that the developmental emergence of circadian sleep enables more complex cognitive processes, including the onset of enduring memories.
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Drosophila , Memoria a Largo Plazo , Animales , Lactante , Humanos , Afecto , Nivel de Alerta , Larva , SueñoRESUMEN
STUDY DESIGN: Retrospective cohort study. OBJECTIVES: This study aims to analyze outcomes and complications of patients with thoracic and lumbar fractures in the setting of ankylosing spinal disorders (ASD) treated with minimally invasive surgery (MIS). METHODS: The operative logs from 2012 to 2019 from one academic, Level I trauma center were reviewed for cases of thoracic and lumbar spinal fractures in patients with ASD treated with a MIS approach. Variables were compared between patients with ankylosing spondylitis (AS), diffuse idiopathic skeletal hyperostosis (DISH), and advanced spondylosis. RESULTS: A total of 48 patients with ASD and concomitant thoracic or lumbar spinal fracture managed with an MIS approach were identified. A total of 11 patients were identified with AS, 21 with DISH, and 16 with advanced spondylosis. A total of 27 (56.3%) patients experienced complications. Complications differed between groups; DISH patients experienced a greater number of post-operative complications compared to AS and advanced spondylosis patients (P = .009). There was no significant difference in length of surgery, estimated blood loss, length of stay, readmission, and reoperation rates between AS and DISH patients. There were 3 mortalities unrelated to the surgery. CONCLUSION: Percutaneous stabilization of patients with ankylosing spinal disorder fractures remains a viable management method. Operative characteristics were similar between AS, DISH, and advanced spondylosis patients; however, DISH patients experienced a greater number of post-operative complications.
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STUDY DESIGN: Retrospective Case Series. OBJECTIVE: This study aims to evaluate readmission rates, risk factors, and reason for unplanned 30-day readmissions after thoracolumbar spine trauma surgery. METHODS: A retrospective chart review was conducted for patients undergoing operative treatment for thoracic or lumbar trauma with open or minimally invasive surgical approach at a Level 1 urban trauma center. Patients were divided into two groups based on 30-day readmission status. Reason for readmission, reoperation rates, injury type, trauma severity, and incidence of polytrauma were compared between the two groups. RESULTS: A total of 312 patients, 69.9% male with an average age of 47 ± 19 years were included. The readmitted group included 16 patients (5.1%) of which 9 (56%) were readmitted for medical complications and 7 for surgical complications. Wound complications (31.3% of readmissions) were the most common cause of readmission, followed by non-wound related sepsis (18.9% of readmissions). A total of 6 patients (37.5%) required reoperation; 2 instrumentation failures underwent revision surgery, and 4 wound complications underwent irrigation and debridement. Patients with higher Injury Severity Scale (ISS) were more likely to be readmitted (27.8% vs 22.1%, P = .045). Concomitant lower limb surgery increased odds of readmission (OR, 4.40; 95% CI, 1.10-17.83; P = .037). CONCLUSION: Spine trauma 30-day readmission rate was 5.1%, comparable to those reported in the elective spine surgery literature. Readmitted patients were more likely to sustain concomitant operative lower limb trauma. Wound complications were the most common cause of readmission, and almost half of the patients were readmitted due to surgery-related complications.
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OBJECTIVE: Flowable gelatin-based matrices with thrombin for hemostatic control are commercially available as Floseal (Baxter International Inc.) and Surgiflo (Ethicon Inc.). The objective of this study is to compare the rate of blood transfusions following the use of Floseal and Surgiflo in lumbar spine surgery. METHODS: Elective lumbar spine surgery patients between September 2019 and March 2021 were identified via CPT codes. Floseal 10 mL (N=102) and Surgiflo matrix 8 mL (N=108) cohorts excluded those younger than 18 years or those who underwent surgeries for infection, trauma, or tumor. The primary outcome was blood transfusion. Surgical complexity was controlled using the Surgical Invasiveness Index and Adult Spinal Deformity Invasiveness Score. The 1:1 propensity score matching was performed using demographic information, Surgical Invasiveness Index, Adult Spinal Deformity Invasiveness Score, and tranexamic acid use. RESULTS: A total of 77 Floseal patients were propensity score matched with 77 Surgiflo patients. There was no difference in the rate of blood transfusion (p=0.441). There was also no difference in operative time, estimated blood loss, or postoperative hemoglobin levels. The Surgiflo cohort used more units per surgery (p=0.004) and cost $102.45 more per surgery. Switching to Floseal saves $102,450 per year per 1000 surgeries. CONCLUSIONS: There was no difference in transfusion rates between using Floseal or Surgiflo for lumbar spine surgery. Surgiflo had higher usage per surgery and costs than Floseal.
RESUMEN
Primary afferent "pain" fibers (nociceptors) are divided into subclasses based on distinct molecular and anatomical features, and these classes mediate noxious modality-specific contributions to behaviors evoked by painful stimuli. Whether the heat and capsaicin receptor transient receptor potential vanilloid-1 (TRPV1) is expressed heterogeneously across several sensory populations, or is selectively expressed by a unique nociceptor subclass, however, is unclear. Here we used two lines of Trpv1 reporter mice to investigate the primary afferent expression of TRPV1, both during development and in the adult. We demonstrate, using Cre-induced lineage tracing, that during development TRPV1 is transiently expressed in a wide range of dorsal root ganglion neurons, and that its expression is gradually refined, such that TRPV1 transcripts become restricted to a specific subset of peptidergic sensory neurons. Finally, the remarkable sensitivity that is characteristic of these reporter mice revealed an innervation of central and peripheral targets by TRPV1+ primary afferents in the adult that is considerably more extensive than has previously been appreciated.