Spatiotemporal analysis of regional and age differences in tuberculosis prevalence in mainland China.

Globally, tuberculosis is a leading cause of infectious disease deaths. China ranks third among the 30 high-burden countries for tuberculosis and accounts for approximately 7.4% of the cases reported worldwide. Since very few studies have investigated the age difference in tuberculosis prevalence in mainland China, therefore, the preliminary characterisation of age differences in tuberculosis patients is not well understood. The data of reported sputum smear-positive, tuberculosis and sputum smear-negative cases in 340 prefectures from mainland China were extracted from the China Information System for Disease Control and Prevention from January 2009 to December 2018. Multiple statistical analysis and GIS techniques were used to investigate the temporal trend and identify the spatial distribution of sputum smear-positive, tuberculosis and sputum smear-negative cases in the study area. The results showed that the incidence of sputum smear-positive and tuberculosis has dropped to a stable level, while sputum smear-negative exhibited a rising trend. Additionally, sputum smear-positive, tuberculosis and sputum smear-negative are still highly prevalent in northwestern and southwestern regions of China. Interestingly, the young adult group (20-50 age) and elder group (>50 age) are more susceptible to being infected with tuberculosis, while lower infection levels were recorded in the juvenile group (<20 age). The present study investigated the temporal-spatial distribution of sputum smear-positive, tuberculosis and sputum smear-negative cases in mainland China before the COVID-19 pandemic breakout, which would help the government agency establish an effective mechanism of tuberculosis prevention in high-risk periods and high-risk areas in the study region.

Phytotherapeutic options for the treatment of epilepsy: pharmacology, targets, and mechanism of action.

Epilepsy is one of the most common, severe, chronic, potentially life-shortening neurological disorders, characterized by a persisting predisposition to generate seizures. It affects more than 60 million individuals globally, which is one of the major burdens in seizure-related mortality, comorbidities, disabilities, and cost. Different treatment options have been used for the management of epilepsy. More than 30 drugs have been approved by the US FDA against epilepsy. However, one-quarter of epileptic individuals still show resistance to the current medications. About 90% of individuals in low and middle-income countries do not have access to the current medication. In these countries, plant extracts have been used to treat various diseases, including epilepsy. These medicinal plants have high therapeutic value and contain valuable phytochemicals with diverse biomedical applications. Epilepsy is a multifactorial disease, and therefore, multitarget approaches such as plant extracts or extracted phytochemicals are needed, which can target multiple pathways. Numerous plant extracts and phytochemicals have been shown to treat epilepsy in various animal models by targeting various receptors, enzymes, and metabolic pathways. These extracts and phytochemicals could be used for the treatment of epilepsy in humans in the future; however, further research is needed to study the exact mechanism of action, toxicity, and dosage to reduce their side effects. In this narrative review, we comprehensively summarized the extracts of various plant species and purified phytochemicals isolated from plants, their targets and mechanism of action, and dosage used in various animal models against epilepsy.

Protocol for induction of heterosynaptic long-term potentiation in the mouse hippocampus via dual-opsin stimulation technique.

Cholecystokinin (CCK) is the most abundant neuropeptide that broadly regulates the physiological status of animals. Here, we present a two-color laser theta burst stimulation (L-TBS) protocol for simultaneous activation of Schaffer collateral and perforant pathway in the hippocampus of CCK Cre mice. We describe steps for heterosynaptic long-term potentiation induction by L-TBS. This technique allows for the examination of the neurotransmitter roles in synaptic modulation and facilitates the exploration of pathological mechanisms in genetic models of brain disorders in mice. For complete details on the use and execution of this protocol, please refer to Su et al.1.

Visually or auditorily induced seizures involve the activation of nonhippocampal brain areas and hippocampal removal does not alleviate seizures in a mouse model of temporal lobe epilepsy.

OBJECTIVE: Several studies have attributed epileptic activities in temporal lobe epilepsy (TLE) to the hippocampus; however, the participation of nonhippocampal neuronal networks in the development of TLE is often neglected. Here, we sought to understand how these nonhippocampal networks are involved in the pathology that is associated with TLE disease. METHODS: A kainic acid (KA) model of temporal lobe epilepsy was induced by injecting KA into dorsal hippocampus of C57BL/6J mice. Network activation after spontaneous seizure was assessed using c-Fos expression. Protocols to induce seizure using visual or auditory stimulation were developed, and seizure onset zone (SOZ) and frequency of epileptic spikes were evaluated using electrophysiology. The hippocampus was removed to assess seizure recurrence in the absence of hippocampus. RESULTS: Our results showed that cortical and hippocampal epileptic networks are activated during spontaneous seizures. Perturbation of these networks using visual or auditory stimulation readily precipitates seizures in TLE mice; the frequency of the light-induced or noise-induced seizures depends on the induction modality adopted during the induction period. Localization of SOZ revealed the existence of cortical and hippocampal SOZ in light-induced and noise-induced seizures, and the development of local and remote epileptic spikes in TLE occurs during the early stage of the disease. Importantly, we further discovered that removal of the hippocampi does not stop seizure activities in TLE mice, revealing that seizures in TLE mice can occur independent of the hippocampus. SIGNIFICANCE: This study has shown that the network pathology that evolves in TLE is not localized to the hippocampus; rather, remote brain areas are also recruited. The occurrence of light-induced or noise-induced seizures and epileptic discharges in epileptic mice is a consequence of the activation of nonhippocampal brain areas. This work therefore demonstrates the fundamental role of nonhippocampal epileptic networks in generating epileptic activities with or without the hippocampus in TLE disease.

Entorhinohippocampal cholecystokinin modulates spatial learning by facilitating neuroplasticity of hippocampal CA3-CA1 synapses.

The hippocampus is broadly impacted by neuromodulations. However, how neuropeptides shape the function of the hippocampus and the related spatial learning and memory remains unclear. Here, we discover the crucial role of cholecystokinin (CCK) in heterosynaptic neuromodulation from the medial entorhinal cortex (MEC) to the hippocampus. Systematic knockout of the CCK gene impairs CA3-CA1 LTP and space-related performance. The MEC provides most of the CCK-positive neurons projecting to the hippocampal region, which potentiates CA3-CA1 long-term plasticity heterosynaptically in a frequency- and NMDA receptor (NMDAR)-dependent manner. Selective inhibition of MEC CCKergic neurons or downregulation of their CCK mRNA levels also impairs CA3-CA1 LTP formation and animals' performance in the water maze. This excitatory extrahippocampal projection releases CCK upon high-frequency excitation and is active during animal exploration. Our results reveal the critical role of entorhinal CCKergic projections in bridging intra- and extrahippocampal circuitry at electrophysiological and behavioral levels.

Interhemispheric cortical long-term potentiation in the auditory cortex requires heterosynaptic activation of entorhinal projection.

Long-term potentiation (LTP), which underlies learning and memory, can be induced by high-frequency electrical stimulation (HFS or HFES) and is thought to occur at the synapses of efferent projection. Here, the contralateral connectivity in mice auditory cortex was investigated to reveal the fundamental corticocortical connection properties. After HFES, plasticity was not observed at the terminal synapses at the recording site. The optogenetic HFS at the recording site of the interhemispheric cortical projections could not induce LTP, but HFES at the recording site could induce the interhemispheric cortical LTP. Our subsequent results uncovered that it is the cholecystokinin (CCK) released from the entorhino-neocortical pathway induced by HEFS that modulates the neuroplasticity of the afferent projections, including interhemispheric auditory cortical afferents. Our study illustrates a heterosynaptic mechanism as the basis for cortical plasticity. This regulation might contribute new spots for the understanding and treatment of neurological disorders.

Advances in the Electrophysiological Recordings of Long-Term Potentiation.

Understanding neuronal firing patterns and long-term potentiation (LTP) induction in studying learning, memory, and neurological diseases is critical. However, recently, despite the rapid advancement in neuroscience, we are still constrained by the experimental design, detection tools for exploring the mechanisms and pathways involved in LTP induction, and detection ability of neuronal action potentiation signals. This review will reiterate LTP-related electrophysiological recordings in the mammalian brain for nearly 50 years and explain how excitatory and inhibitory neural LTP results have been detected and described by field- and single-cell potentials, respectively. Furthermore, we focus on describing the classic model of LTP of inhibition and discuss the inhibitory neuron activity when excitatory neurons are activated to induce LTP. Finally, we propose recording excitatory and inhibitory neurons under the same experimental conditions by combining various electrophysiological technologies and novel design suggestions for future research. We discussed different types of synaptic plasticity, and the potential of astrocytes to induce LTP also deserves to be explored in the future.

Streamlining and Consistency in Surgery: Lean Six Sigma to Improve Operating Room Efficiency.

BACKGROUND: Improving perioperative efficiency helps reduce unnecessary surgical expenditure, increase operating room throughput, improve patient safety, and enhance staff and patient satisfaction. Lean Six Sigma (LSS) is a quality improvement model that has been successfully applied to eliminate inefficiencies in the business sector but has not yet been widely adopted in medicine. This study investigates the adaptation of LSS to improve operative efficiency for plastic surgery procedures. METHODS: The authors followed the define, measure, analyze, improve, and control phases to implement LSS. The key outcome measures gathered were operative times, including the cut-to-close time, and the total time the patient spent in the operating room. RESULTS: The study included a total of 181 patients who underwent immediate bilateral deep inferior epigastric perforator flap breast reconstruction between January of 2016 and December of 2019. The LSS interventions were associated with a decrease in total operative time from 636.36 minutes to 530.35 minutes, and a decrease in the time between incision to closure from 555.16 minutes to 458.85 minutes for a bilateral mastectomy with immediate deep inferior epigastric artery flap breast reconstruction. CONCLUSIONS: This study demonstrates that LSS is useful to improve perioperative efficiency during complex plastic surgery procedures. The workflow of the procedure was improved by determining the optimal spatial positioning and distinct roles for each surgeon and preparing surgeon-specific surgical trays. Two process maps were developed to visualize the positioning of the surgeons during each stage of the procedure and depict the parallel workflow that helped improve intraoperative efficiency.

Early Experience With Neutralizing Monoclonal Antibody Therapy for COVID-19: Retrospective Cohort Survival Analysis and Descriptive Study.

BACKGROUND: Neutralizing monoclonal antibody (MAB) therapies may benefit patients with mild to moderate COVID-19 at high risk for progressing to severe COVID-19 or hospitalization. Studies documenting approaches to deliver MAB infusions and demonstrating their efficacy are lacking. OBJECTIVE: We describe our experience and the outcomes of almost 3000 patients who received MAB infusion therapy at Northwell Health, a large integrated health care system in New York. METHODS: This is a descriptive study of adult patients who received MAB therapy between November 20, 2020, to January 31, 2021, and a retrospective cohort survival analysis comparing patients who received MAB therapy prior to admission versus those who did not. A multivariable Cox model with inverse probability weighting according to the propensity score including covariates (sociodemographic, comorbidities, and presenting vital signs) was used. The primary outcome was in-hospital mortality; additional evaluations included emergency department use and hospitalization within 28 days of a positive COVID-19 test for patients who received MAB therapy. RESULTS: During the study period, 2818 adult patients received MAB infusion. Following therapy and within 28 days of a COVID-19 test, 123 (4.4%) patients presented to the emergency department and were released, and 145 (5.1%) patients were hospitalized. These 145 patients were compared with 200 controls who were eligible for but did not receive MAB therapy and were hospitalized. In the MAB group, 16 (11%) patients met the primary outcome of in-hospital mortality, versus 21 (10.5%) in the control group. In an unadjusted Cox model, the hazard ratio (HR) for time to in-hospital mortality for the MAB group was 1.38 (95% CI 0.696-2.719). Models adjusting for demographics (HR 1.1, 95% CI 0.53-2.23), demographics and Charlson Comorbidity Index (HR 1.22, 95% CI 0.573-2.59), and with inverse probability weighting according to propensity scores (HR 1.19, 95% CI 0.619-2.29) did not demonstrate significance. The hospitalization rate was 4.4% for patients who received MAB therapy within 0 to 4 days, 5% within 5 to 7 days, and 6.1% in ≥8 days of symptom onset (P=.15). CONCLUSIONS: Establishing the capability to provide neutralizing MAB infusion therapy requires substantial planning and coordination. Although this therapy may be an important treatment option for early mild to moderate COVID-19 in patients who are at high risk, further investigations are needed to define the optimal timing of MAB treatment to reduce hospitalization and mortality.

Joint-Venture Ambulatory Surgery Centers: The Perfect Partnership.

BACKGROUND: Ambulatory surgery growth has increased in the last few decades as ambulatory surgery centers have been shown to succeed in cost efficiencies through their smaller size and breadth, specialization of care, and ability to quickly participate in perioperative process improvement and education. METHODS: A 5-year retrospective fiscal review was performed for all Northwell Health-physician ambulatory surgery center joint ventures. The outcome measures studied included model of ownership, specialty types, and gross revenue. Additional facility characteristics were studied, including growth trajectory, facility size, and cost to build a de novo facility. RESULTS: Eleven free-standing ambulatory surgery centers were identified at Northwell Health during the 5-year study period. The total gross revenue for all Northwell clinical joint ventures for 2019 alone was $102,854,000. Northwell Health is a majority stakeholder in eight of their joint venture ambulatory surgery centers, with an average Northwell ownership of 53 percent and an average number of physician owners per facility of 11. The number of hospital-physician joint-venture ambulatory surgery centers grew from two to 11 facilities during the study period (450 percent). Surgical volume followed a similar trajectory, increasing 295 percent over the same time period. CONCLUSIONS: The ambulatory surgery center setting provides a vast number of possibilities for key stakeholders, including patients themselves, to benefit from financial and clinical efficiencies. Ambulatory surgery centers have been popular, as they meet patient expectations for convenience of elective surgery, reduce payer and clinical pressures to minimize length of stay in hospitals, and achieve similar or higher quality care with less intense resources.

Peripheral axonopathy in sciatic nerve of adult Wistar rats following exposure to vanadium.

Depletion of myelin and neurobehavioural deficits are indications that vanadium crosses the blood-brain barrier and such neurotoxic effects of vanadium on the brain of Wistar rats have been elucidated. The effect however on the peripheral nerves, is yet to be reported. Thus, this work was designed to evaluate the axonal and myelin integrity of sciatic nerves in Wistar rats following exposure to vanadium. Ten male Wistar rats were exposed to 3 mg/kg body weight of sodium metavanadate for 7 days, subjected to rearing and forelimb grip behavioural tests, and sciatic nerves processed for histology (haematoxylin and eosin, cresyl violet, and luxol fast blue). Dystrophic axons with vesiculated myelin, thinned myelin sheath, and demyelinated axons were observed in the vanadium exposed rats, suggestive of axonopathy, classified as fourth-degree nerve injury. Lower behavioural scores were recorded for vanadium-dosed rats; thus, corroborating histological pictures observed of the sciatic nerves. Authors posit that vanadium crossed the "blood-nerve" barrier and caused the observed axonal pathologies and myelin depletion in the sciatic nerves of these rodents with resultant motor deficits. The present paper discusses possible motor deficits and the likely public health importance in regions with crude oil pollution and gas flaring rich in vanadium products.