Medico-Legal Implications of Video Recordings of Clinic Visits in Malpractice Claims Against Medical Providers.

OBJECTIVE: Although audio-video recordings of clinic visits improve patient satisfaction and recall, the associated presumed risk of increased malpractice claims limits their use. In this study, we identified whether video recording clinic visits was associated with increases in professional liability claims. METHODS: From 2015 to 2017, the institution's loss run was analyzed, and the rates of medical malpractice claims per physician-year were compared between physicians who used video recordings of clinic visits (V-RoCs) and those who did not. The term "users" was applied to all physicians whose mean percentage of patient visits with video recording was greater than the mean percentage for the practice overall. RESULTS: Over three years, 15,254 patients used V-RoCs. The use of video recordings for clinic visits increased at a rate of 23% per year. No association was found between video recordings and increased malpractice claims. The rate of all claims between users and nonusers did not differ significantly (P=0.66). Of seven paid claims or lawsuits from 2000 to 2017, none were against physicians who used video recordings. CONCLUSION: Video recording of patient-physician encounters was not associated with an increase in malpractice lawsuits. According to federal law, a patient can legally record a clinic encounter without physician consent, which has many ethical implications. Formalizing the recording process is beneficial for both parties and allows the resource to be used to its maximum potential.

Emergency decompressive surgery in patients with transtentorial brain herniation and pupillary abnormalities: the importance of improved pupillary response after osmotherapy and surgery.

OBJECTIVE: The predictors of survival and functional recovery following emergency decompressive surgery in patients with transtentorial brain herniation, particularly those with pupillary abnormalities, have not been established. In this study, the authors aimed to assess the outcome of patients with intracranial mass lesions, transtentorial brain herniation, and nonreactive mydriasis, following emergency surgical decompression. METHODS: A retrospective chart review was performed of all patients with transtentorial herniation and pupillary abnormalities who underwent craniotomy or craniectomy at two trauma and stroke centers between 2016 and 2022. The functional outcome was determined using the modified Rankin Scale (mRS). RESULTS: Forty-three patients, 34 men and 9 women with a mean age of 47 years (range 16-92 years), were included. The underlying etiology was traumatic brain injury in 33 patients, hemorrhagic stroke in 8 patients, and tumor in 2 patients. The median preoperative Glasgow Coma Scale score was 3 (range 3-8), and the median midline shift was 9 mm (range 1-29 mm). Thirty-two patients (74.4%) had bilaterally fixed and dilated pupils. The median time to surgery (from pupillary changes) was 133 minutes (mean 169 minutes, range 30-900 minutes). Eighteen patients (41.9%) died postoperatively. After a median follow-up of 12 months (range 3-12 months), 11 patients (26.8%) had a favorable functional outcome, while 10 remained severely disabled (mRS score 5). On univariate analysis, younger age (p < 0.001), less midline shift (p = 0.049), and improved pupillary response after osmotic therapy (p < 0.01) or decompressive surgery (p < 0.001) were associated with favorable outcomes at 3 months. CONCLUSIONS: With aggressive medical and surgical management, patients with transtentorial brain herniation, including those with bilaterally fixed and dilated pupils, may have considerable rates of survival and functional recovery. Young age, less midline shift, and improved pupillary response following osmotic therapy or decompressive surgery are favorable prognosticators.

Opportunities and constraints for cleaner production policy in the developing world: a case study of Sindh Region, Pakistan.

The current industrial and economic activities in Sindh Province, Pakistan, polluted the region's water, air, soil, and marine resources. However, there is a rising demand for eco-friendly production, and it is important to develop new policies and tools to combat environmental degradation and enhance economic development. Cleaner Production (CP) provides opportunities to address many of these issues. Employed method for this study was based on three approaches: a literature review and stakeholder mapping; a collection of data and information from key stakeholders through focal group discussions, consultative workshops, and one-on-one meetings; and analysis and synthesis of data that were gathered from different sources. The analysis of collected information provides an overview of CP strategies moving forward. Participant workshops gave in-depth information on policy implementation, technological impediments to methods that have been employed elsewhere, and needed capacity building as well as financial consequences of policy implementation. Through increasing financial resources and institutional resources, the expansion of CP will help to replace the conventional methods of waste treatment with an eco-efficiency approach to preventing pollution at the source, thus reducing the need for expensive pollution control and management costs for environmental compliance. Experiences, achievements, and implementation pitfalls from this study can provide a lesson to other developing countries to improve their economic and environmental sustainability.

Redundant nerve roots indicate higher degree of stenosis in lumbar spine stenotic patients.

OBJECTIVES: Redundant Nerve Root (RNR) is a tortuous and elongated radiological appearance of cauda equina on Magnetic Resonance Imaging (MRI) in Lumbar Spinal Canal Stenosis (LSCS) patients. This study evaluated preoperative spinal morphometry associated with the development of RNR. METHODS: The retrospective cohort was conducted at The Aga Khan University Hospital, and included patients undergoing decompressive spinal surgery secondary to degenerative LSCS in 2015. The patients were divided into two groups with respect to the presence of preoperative RNR. Spinal morphometry was defined by several radiological parameters, including areas of dural sac (DSA), spinal canal, spinal foramen, facets, and spinal joints, and bilateral angles based on vertebral anatomy. RESULTS: A total of 55 patients were enrolled with a mean age of 57.1 years, in which 22 (40%) expressed RNR in their MRI. The RNR group had significantly lower mean DSA (59.64 vs 84.01 mm2; p = 0.028), bilateral posterior facet angle (Right: 33.84 vs 46.21, p = 0.004; Left: 36.43 vs 43.80, p = 0.039) and higher bilateral anterior facet angles (Right: 54.85 vs 44.57, p = 0.026; Left: 55.27 vs 46.36, p = 0.050) compared to the non-RNR group. The other bidimensional and angular parameters did not observe any statistical difference between the two groups. CONCLUSION: RNR was associated with a higher degree of stenosis in patients with LSCS. Bilateral anterior and posterior facets angles contribute to its development, indicating particular spinal morphology to be vulnerable to the stenotic disease.

Effect of Rumex dentatus on Gastrointestinal Protection and Toxicology in Rodents via Investigating H+/K+-ATPase, Calcium Channels, and PDE Mediated Signaling.

This present study aims to delineate Rumex dentatus crude extract (Rd.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rd.n-Hex, Rd.ETAC, and Rd.Aq), and emodin for antidiarrheal, antisecretory effects, anti-spasmodic, gastrointestinal transient time, anti-H. pylori, antiulcer effects, and toxicology. Plant extracts attributed dose-dependent protection against castor oil-induced diarrhea and dose-dependently inhibited intestinal fluid secretions in mice. They decreased the distance transverse by charcoal in the gastrointestinal transit model in rats. In rabbit jejunum preparations, it causes a concentration-dependent relaxation of both spontaneous and K+ (80 mM)-induced contraction, Rd.n-Hex and verapamil were relatively potent against K+-induced contractions and shifted the Ca2+ concentration-response curves (CRCs) to the right, Rd.Cr and Rd.ETAC shifted the isoprenaline-induced inhibitory CRCs to the left, showing potentiating effect similar to papaverine. Rd.n-Hex showed anti-H. pylori effect. Extracts and emodin also show an inhibitory effect against H+/K+-ATPase. Rumex dentatus showed a gastroprotective and antioxidant effect. Histopathological evaluation showed improvement in cellular architecture and decrease in the expression of inflammatory markers such as cyclooxygenase (COX2), tumor necrosis factor (TNF-α), and phosphorylated nuclear factor kappa B (p-NFƙB), validated through immunohistochemistry, ELISA, and western blot techniques. In RT-PCR, it decreases H+/K+-ATPase mRNA levels. Rumex dentatus was analyzed for certain safety aspects and exhibited a relative safety profile as no impairment was observed in kidneys, heart, liver, and brain further assisted by biochemical and hematological analysis. Docking studies revealed that emodin against H+/K+-ATPase pump and voltage gated L-type calcium channel showed E-value of -7.9 and -7.4 kcal/mol, respectively. MD simulations and molecular mechanics Poisson Boltzmann surface area and molecular mechanics Generalized Born surface area MMPBSA/GBSA findings are consistent with the in-vitro, in-vivo, and docking results. In conclusion, Rumex dentatus extracts and its phytoconstituent could be considered a potent antioxidant and anti-inflammatory drug candidates that possess anti-diarrheal, anti-secretary, antispasmodic, anti-H. pylori, and anti-ulcer potential. Toxicity studies were done according to OECD standards 425. It belongs to group 5 (LD50 > 2000 mg/kg), which suggests that it is in the lower toxicity class.

Spinal Radiology associated with Redundant Nerve Roots of cauda equina in lumbar spine stenosis.

OBJECTIVES: Redundant Nerve Roots (RNR) is a common radiological observation of elongated tortuous appearance of cauda equina nerve roots in sagittal MRI. It is considered a poor prognostic factor, but the associated spinal morphometry remains unfamiliar. METHODS: A retrospective cohort study was conducted at the Aga Khan University Hospital, Pakistan. Patients, aged 18 or above, undergoing decompressive spinal surgery due to degenerative Lumbar Spinal Canal Stenosis (LSCS) in 2015 were included. Patients were divided in groups as per presence of RNR and assessed for spinal morphometric parameters. RESULTS: Fifty-two patients, aged 57.52 ± 12.08 years, were enrolled in the study. The patients in RNR group were older than those in non-RNR group (p = 0.023). RNR was significantly associated with sedimentation sign (15 vs 11; p = 0.011), as well as L2/L3 (12 vs 9; p = 0.043) and L3/L4 (18 vs 18; p = 0.034) stenosis. Ligamentum flavum hypertrophy at the most stenotic level was more common in the RNR group (20 vs 19; p = 0.006). The only quantitative parameter statistically associated with RNR was lower ligamentous interfacet distance (5.07 ± 1.95 vs 8.07 ± 4.26 mm; p = 0.010). All other parameters did not contribute to the development of RNR in LSCS patients. The multivariate model revealed significant contribution of age, male sex, ligamentous interfacet distance and disc bulge to develop RNR. CONCLUSION: Certain spinal morphometric parameters contribute towards RNR formation, which represents higher degree of spinal stenosis. These parameters, along with RNR, should be regularly reported for preoperative consideration of LSCS management.

Upadacitinib protects against cisplatin-induced renal and hepatic dysfunction without impairing its anticancer activity.

Cisplatin-induced renal and hepatic dysfunctions are major drawbacks and obstacles to its clinical applications. Induction of inflammation is a part of its molecular mechanism of toxicity. The impact of upadacitinib, a selective JAK1-inhibitory anti-inflammatory agent, on cisplatin-induced adverse effects, histopathologic changes, kidney and liver functions, oxidative stress, and inflammatory biomarkers were investigated compared to silymarin and losartan in male Wistar rats. The animals were treated with upadacitinib (10 mg/kg/day) for two weeks in addition to one dose of cisplatin (10 mg/kg) on the seventh day of treatment. The liver and kidney functions as well as the oxidative biomarkers and inflammatory burst, were biochemically measured. Upadacitinib pre-treatment significantly improved liver function markers (ALT and AST) and inhibited cisplatin-induced lipid profile aberrations (total cholesterol and triglycerides). Moreover, it protected the kidney functions as indicated by blood urea nitrogen, serum creatinine, creatinine clearance, and albumin levels. Upadacitinib also attenuated cisplatin-induced hepatic and renal inflammatory events, as indicated by the reduction of MDA and TNFα levels. In addition, it improved the superoxide dismutase (SOD) activity. Upadacitinib effectively diminished histopathologic structural damage in liver and kidney tissues. Western blotting of NF-kB and p-Akt confirmed the renoprotective effect of upadacitinib. Furthermore, the cell viability assay shows that upadacitinib did not have any inhibitory activity on cisplatin anticancer potency in MCF-7 and A549 cells. Moreover, upadacitinib has improved the potency of cisplatin against lung cancer cells in a dose-dependent pattern. These results highlight upadacitinib's protective effects from cisplatin-induced toxicity without impairing its anticancer activity.

Single-position prone lateral transpsoas approach: early experience and outcomes.

OBJECTIVE: Lateral lumbar interbody fusion (LLIF) via a transpsoas approach is a workhorse minimally invasive approach for lumbar arthrodesis that is often combined with posterior pedicle screw fixation. There has been increasing interest in performing single-position surgery, allowing access to the anterolateral and posterior spine without requiring patient repositioning. The feasibility of the transpsoas approach in patients in the prone position has been reported. Herein, the authors present a consecutive case series of all patients who underwent single-position prone transpsoas LLIF performed by an individual surgeon since adopting this approach. METHODS: A retrospective review was performed of a consecutive case series of adult patients (≥ 18 years old) who underwent single-position prone LLIF for any indication between October 2019 and November 2020. Pertinent operative details (levels, cage use, surgery duration, estimated blood loss, complications) and 3-month clinical outcomes were recorded. Intraoperative and 3-month postoperative radiographs were reviewed to assess for interbody subsidence. RESULTS: Twenty-eight of 29 patients (97%) underwent successful treatment with the prone lateral approach over the study interval; the approach was aborted in 1 patient, whose data were excluded. The mean (SD) age of patients was 67.9 (9.3) years; 75% (21) were women. Thirty-nine levels were treated: 18 patients (64%) had single-level fusion, 9 (32%) had 2-level fusion, and 1 (4%) had 3-level fusion. The most commonly treated levels were L3-4 (n = 15), L2-3 (n = 12), and L4-5 (n = 11). L1-2 was fused in 1 patient. The mean operative time was 286.5 (100.6) minutes, and the mean retractor time was 29.2 (13.5) minutes per level. The mean fluoroscopy duration was 215.5 (99.6) seconds, and the mean intraoperative radiation dose was 170.1 (94.8) mGy. Intraoperative subsidence was noted in 1 patient (4% of patients, 3% of levels). Intraoperative lateral access complications occurred in 11% of patients (1 cage repositioning, 2 inadvertent ruptures of anterior longitudinal ligament). Subsidence occurred in 5 of 22 patients (23%) with radiographic follow-up, affecting 6 of 33 levels (18%). Postoperative functional testing (Oswestry Disability Index, SF-36, visual analog scale-back and leg pain) identified significant improvement. CONCLUSIONS: This single-surgeon consecutive case series demonstrates that this novel technique is well tolerated and has acceptable clinical and radiographic outcomes. Larger patient series with longer follow-up are needed to further elucidate the safety profile and long-term outcomes of single-position prone LLIF.

Comparative analysis of the combined petrosal and the pretemporal transcavernous anterior petrosal approach to the petroclival region.

OBJECTIVE: The combined petrosal (CP) approach has been traditionally used to resect petroclival meningioma (PCM). The pretemporal transcavernous anterior petrosal (PTAP) approach has emerged as an alternative. A quantitative comparison of both approaches has not been made. This anatomical study compared the surgical corridors afforded by both approaches and identified key elements of the approach selection process. METHODS: Twelve cadaveric specimens were dissected, and 10 were used for morphometric analysis. Groups A and B (n = 5 in each) underwent the CP and PTAP approaches, respectively. The area of drilled clivus, lengths of cranial nerves (CNs) II-X, length of posterior circulation vessels, surgical area of exposure of the brainstem, and angles of attack anterior and posterior to a common target were measured and compared. RESULTS: The area of drilled clivus was significantly greater in group A than group B (mean ± SD 88.7 ± 17.1 mm2 vs 48.4 ± 17.9 mm2, p < 0.01). Longer segments of ipsilateral CN IV (52.4 ± 2.33 mm vs 46.5 ± 3.71 mm, p < 0.02), CN IX, and CN X (9.91 ± 3.21 mm vs 0.00 ± 0.00 mm, p < 0.01) were exposed in group A than group B. Shorter portions of CN II (9.31 ± 1.28 mm vs 17.6 ± 6.89 mm, p < 0.02) and V1 (26.9 ± 4.62 mm vs 32.4 ± 1.93 mm, p < 0.03) were exposed in group A than group B. Longer segments of ipsilateral superior cerebellar artery (SCA) were exposed in group A than group B (36.0 ± 4.91 mm vs 25.8 ± 3.55 mm, p < 0.02), but there was less exposure of contralateral SCA (0.00 ± 0.00 mm vs 7.95 ± 3.33 mm, p < 0.01). There was no statistically significant difference between groups with regard to the combined area of the exposed cerebral peduncles and pons (p = 0.75). Although exposure of the medulla was limited, group A had significantly greater exposure of the medulla than group B (p < 0.01). Finally, group A had a smaller anterior angle of attack than group B (24.1° ± 5.62° vs 34.8° ± 7.51°, p < 0.03). CONCLUSIONS: This is the first study to quantitatively identify the advantages and limitations of the CP and PTAP approaches from an anatomical perspective. Understanding these data will aid in designing maximally effective yet minimally invasive approaches to PCM.

Bergapten Attenuates Nitroglycerin-Induced Migraine Headaches through Inhibition of Oxidative Stress and Inflammatory Mediators.

The present study intended to examine the effect of bergapten and possible mechanisms involved in the treatment of migraine-associated symptoms in the rat model. Five doses of nitroglycerin (10 mg/kg) were injected intraperitoneal to induce migraine headaches in rats with a one-day break between each dose. Treatment groups received nitroglycerin followed after 1 day by bergapten (50 or 100 mg/kg), saline (10 mL/kg), or sumatriptan (50 mg/kg) once daily for 10 days. Behavioral observations were analyzed 2 h after nitroglycerin injections and 1 h 40 min after treatment. The animals were sacrificed 24 h after the last treatment dose. Samples of trigeminal nucleus caudalis (TNC) and cerebral cortex were collected and analyzed for antioxidant activity and expression of inflammatory markers by immunohistochemistry and enzyme-linked immunosorbent assay. Our findings revealed that bergapten notably decreases headache by altering mechanical allodynia, thermal allodynia, light phobicity, and the number of head-scratching incidence in rats. In the cortex and TNC regions, antioxidant factors were restored, and lipid peroxidation was significantly reduced. Furthermore, bergapten decreased the expression of inflammatory markers, such as nuclear factor kappa B (NF-Kb) and tumor necrosis factor-alpha (TNF-α), as evidenced by immunohistochemistry and ELISA. These results suggest that bergapten exhibits headache-relieving activity, possibly mediated through antioxidant and anti-inflammatory pathways.

Posterior Fossa Hemorrhage Following the Use of Low-Molecular-Weight Heparin: Lessons Learned and Recommendations for the Treatment and Prophylaxis of Postoperative Venous Thromboembolism.

Introduction Venous thromboembolism (VTE) is the most common preventable cause of morbidity and mortality among neurosurgery patients. Several studies have concluded that the use of chemical prophylaxis among patients undergoing a craniotomy reduces the incidence of VTE, and it is presumed to be safe. However, these studies do not differentiate between a supratentorial and posterior fossa craniotomy. Furthermore, the prophylactic or therapeutic use of low-molecular-weight heparin (LMWH) has been reported to increase the risk of intracranial hemorrhage. In this study, we describe the clinical details and outcomes for all patients who underwent posterior fossa craniotomy and developed posterior fossa hemorrhage secondary to postoperative use of LMWH during the study period. We also propose recommendations pertaining to postoperative heparin use after posterior fossa surgeries. Methods Data were retrospectively collected for patients presenting with posterior fossa hemorrhage following anticoagulant use among those who previously underwent posterior fossa craniotomy by the senior author (R.W.P.) from January 1, 2011, through December 31, 2018. Results We identified five patients who experienced postoperative hemorrhage while receiving LMWH in the initial setting of posterior fossa craniotomy. After hemorrhaging, four patients had low Glasgow Outcome Scale (GOS) scores (≤3) and failed to return to their baseline neurological status. These four patients had a Glasgow Coma Scale (GCS) score of 15/15 in the immediate postoperative period and received heparin within 72 hours of surgery. Conclusions Based on our findings, there is a possible association between the increased risk of hemorrhage and the early postoperative use of LMWH. The debilitating outcomes among the majority of these patients warrant the cautious use and further investigation of postoperative LMWH to appropriately quantify the risk. Further comparative studies with a larger sample size are required to provide insight into the pathophysiology of our findings.

Proteomic Analysis and In Vivo Studies Reveal the Potential Gastroprotective Effects of CHCl3 and Aqueous Extracts of Ficus palmata.

Ficus palmata is rich in several phytochemicals such as chromone, isoflavones, terpenes, lignans, coumarins, glycosides, and furanocoumarins and have been traditionally used for the management of different gastrointestinal disorders. This research reveals the effects of Ficus palmata fruit extracts-Ficus palmata chloroform (Fp.CHCl3) and Ficus palmata aqueous (Fp.Aq)-on gut activity through in vivo and in vitro analyses. Antidiarrheal and enteropooling assays were analyzed with castor oil-induced diarrhea and intestinal fluid accumulation. Jejunum tissues of rabbits were isolated (antispasmodic) for in vitro experiments. Antimotility was carried out by charcoal meal for determining transient time, and ethanol-induced ulcer assay was used to measure the ulceration of stomach; molecular pathways were assessed through proteomic approach. Fp.CHCl3 and Fp.Aq extracts attributed dose-dependently protection against diarrhea, and intestinal fluid secretions were inhibited dose dependently. Extracts of Fp.CHCl3 and Fp.Aq produced reduction in spontaneous and K+ (at 80 Mm)-induced contractions in isolated jejunum tissues, along with the decreased length covered by charcoal in charcoal meal transient time activity. The extract exhibited gastroprotective outcome in rats and reduced tumor necrotic factor (TNF-α) levels and IL-18, measured by proteomic approach. Morphological studies' results showed that ethanol induced significant gastritis, apoptosis, swelling of mucosa, and hydropic degeneration leading to cellular degeneration and necrosis, observed through staining techniques. Furthermore, ethanol activated the inflammation pathway in all gastric zones by elevating the levels of cyclooxygenase-2, TNF-α, and nuclear factor kappa light-chain enhancer of activated B-cells. Overall results expressed the antidiarrheal, antispasmodic, enteropooling, antimotility, and antiulcer activities of Ficus palmata fruit extract.

Role of redundant nerve roots in clinical manifestations of lumbar spine stenosis.

BACKGROUND: Redundant nerve roots (RNRs) are defined as elongated, thickened, and tortious appearing roots of the cauda equina secondary to lumbar spinal canal stenosis (LSCS). The study compared the clinical and radiological features of patients with LSCS with versus without RNR. METHODS: This retrospective study was performed on 55 patients who underwent decompressive surgery for degenerative LSCS. Patients were divided into two groups based on the presence of RNR in their preoperative magnetic resonance imaging, as evaluated by a radiologist blinded to the study design. Medical records were reviewed for basic demographic, clinical MR presentation, and outcomes utilizing Japanese Orthopaedic Association (JOA) scores. RESULTS: The mean age of enrolled patients was 57.1, with mean follow-up of 4.0 months. RNR was found in 22 (40%) of patients with LSCS. These patients were older than those patients without RNR (62.2 vs. 53.7). Interestingly, there were no statistically significant differences in clinical presentations, duration of symptoms, and outcomes using JOA scores between the two groups. CONCLUSION: RNR is a relatively common radiological finding (i.e., 40%) in patients with LSCS. It is more likely to be observed in older patients. However, no significant differences were noted in clinical presentation and functional outcomes with respect to the presence or absence of RNR.

Enhanced Accumulation of Cisplatin in Ovarian Cancer Cells from Combination with Wedelolactone and Resulting Inhibition of Multiple Epigenetic Drivers.

PURPOSE: Cisplatin resistance is a major concern in ovarian cancer treatment. The aim of this study was to investigate if wedelolactone could perform better in resistant ovarian cancer cells when used in combination with cisplatin. METHODS: Growth inhibitory potential of wedelolactone and cisplatin was investigated through MTT reduction assay in ovarian cancer cell lines including A2780 (sensitive), A2780cisR (cisplatin resistant) and A2780ZD0473R. Resistance factor (RF) of drugs was determined in these three cell lines. Combination index (CI) was calculated as a measure of combined drug action. Effect of this combination on changes in the cellular accumulation of platinum levels and platinum-DNA binding was also determined in vitro using AutoDock Vina while the effect of wedelolactone on inhibition of possible key culprits of resistance including Chk1, CD73, AT tip60, Nrf2, Brd1, PCAF, IGF1, mTOR1 and HIF2α was investigated in silico. RESULTS: Cisplatin and wedelolactone showed a dose-dependent growth inhibitory effect. RF value of wedelolactone was 1.1 in the case of A2780cisR showing its potential to bring more cell death in cisplatin-resistant cells. CI values were found to vary showing antagonistic to additive outcomes. Additive effect was observed for all sequences of administration (0/0, 0/4 and 4/0 h) in A2780cisR. Enhanced cellular accumulation of cisplatin was observed in parent and resistant cells on combination. Docking results revealed that among the selected oncotargets, Chk1, CD73, Nrf2, PCAF and AT tip60 were more vulnerable to wedelolactone than their respective standard inhibitors. CONCLUSION: These findings have shown that additive outcome of drug combination in A2780cisR and raised levels of platinum accumulation followed a clear pattern. This observation indicates that the presence of wedelolactone might have contributed to sensitize A2780cisR. However, in silico results point to the possible effects of this compound on epigenetic factors involving tumor microenvironment, epithelial mesenchymal transition, and immune-checkpoint kinases.

Comparison of Surgical Outcomes and Recurrence Rates of Cystic and Solid Vestibular Schwannomas.

Objective Cystic vestibular schwannomas (CVSs) are anecdotally believed to have worse clinical and tumor-control outcomes than solid vestibular schwannomas (SVSs); however, no data have been reported to support this belief. In this study, we characterize the clinical outcomes of patients with CVSs versus those with SVSs. Design This is a retrospective review of prospectively collected data. Setting This study is set at single high-volume neurosurgical institute. Participants We queried a database for details on all patients diagnosed with vestibular schwannomas between January 2009 and January 2014. Main Outcome Measures Records were retrospectively reviewed and analyzed using univariate and multivariate analyses to study the differences in clinical outcomes and tumor progression or recurrence. Results Of a total of 112 tumors, 24% ( n = 27) were CVSs and 76% ( n = 85) were SVSs. Univariate analysis identified the extent of resection, Koos grade, and tumor diameter as significant predictors of recurrence ( p ≤ 0.005). However, tumor diameter was the only significant predictor of recurrence in the multivariate analysis ( p = 0.007). Cystic change was not a predictor of recurrence in the univariate or multivariate analysis ( p ≥ 0.40). Postoperative facial nerve and hearing outcomes were similar for both CVSs and SVSs ( p ≥ 0.47). Conclusion Postoperative facial nerve outcome, hearing, tumor progression, and recurrence are similar for patients with CVSs and SVSs. As CVS growth patterns and responses to radiation are unpredictable, we favor microsurgical resection over radiosurgery as the initial treatment. Our data do not support the commonly held belief that cystic tumors behave more aggressively than solid tumors or are associated with increased postoperative facial nerve deficits.

Enhanced neuroprotective and antidepressant activity of curcumin-loaded nanostructured lipid carriers in lipopolysaccharide-induced depression and anxiety rat model.

The present study aims to develop curcumin-loaded nanostructured lipid carriers (CUR-NLCs) and investigate their neuroprotective effects in lipopolysaccharide (LPS)-induced depression and anxiety model. Nanotemplate engineering technique was used to prepare CUR-NLCs with Compritol 888 ATO and oleic acid as solid and liquid lipid, respectively. Poloxamer 188, Tween 80 and Span 80 were used as stabilizing agents for solid-liquid lipid core. The physicochemical parameters of CUR-NLCs were determined followed by in vitro drug release and in vivo neuroprotective activity in rats. The optimized CUR-NLCs demonstrated nanometric particle size of 147.8 nm, surface charge of -32.8 mV and incorporation efficiency of 91.0%. CUR-NLCs showed initial rapid followed by a sustained drug release reaching up to 73% after 24 h. CUR-NLCs significantly elevated struggling time and decreased immobility time in forced swim and tail suspension tests. A substantial increase in time spent and number of entries into the light and open compartments was observed in light-dark box and elevated plus maze models. CUR-NLCs improved the tissue architecture and suppressed the expression of p-NF-κB, TNF-α and COX-2 in brain tissues from histological and immunohistochemical analysis. CUR-NLCs improved the neuroprotective effect of curcumin and can be used as a potential therapeutics for depression and anxiety.

Prone Single-Position Lateral Lumbar Interbody Fusion With Posterior Decompression and Pedicle Screw Fixation for the Treatment of Grade II Spondylolisthesis: 2-Dimensional Operative Video.

Lateral lumbar interbody fusion (LLIF) provides indirect decompression without disruption of the posterior elements. It involves a larger implant footprint than that of posterior approaches. LLIF is typically performed with the patient in the lateral decubitus position. When a posterior fixation is indicated, a second-stage procedure is performed with the patient in the prone position. Single-position surgery provides the potential advantage of decreased operative time because both procedures can be performed without patient repositioning. Single-position LLIF and posterior fixation in the prone position have not been well validated to date. Herein, techniques for LLIF, percutaneous pedicle screw fixation, and facetectomy in the prone position are shown. A 76-yr-old woman with osteoporosis presented with severe back and bilateral leg pain refractory to conservative management and imaging findings of grade 2 dynamic anterolisthesis at L4-L5 with severe stenosis. She underwent LLIF with percutaneous pedicle screw fixation and facetectomy. She was placed on a Jackson table in the prone position for the entire procedure, which was performed in a single stage. Percutaneous pedicle screws were placed, followed by a left-sided minimally invasive facetectomy. A left-sided retroperitoneal transpsoas approach was used to perform the LLIF in standard fashion. Finally, the rods were locked into place. Postoperatively, the patient was neurologically stable, and imaging confirmed good hardware placement. At the 6-wk follow-up, the patient was doing well. This case demonstrates the feasibility of performing LLIF and posterior fixation in a single stage in the prone position. The patient provided informed consent. Used with permission from Barrow Neurological Institute.

Natural Dietary Supplement, Carvacrol, Alleviates LPS-Induced Oxidative Stress, Neurodegeneration, and Depressive-Like Behaviors via the Nrf2/HO-1 Pathway.

PURPOSE: Major depressive disorder (MDD) is a debilitating human health condition characterized by mood swings and is associated with a high probability of suicide attempts. Several studies have reported a role of neuroinflammation in MMD, yet the efficacy of natural drug substances on neuroinflammation-associated depression has not been well-investigated. The present study examined the neuroprotective effects of carvacrol on lipopolysaccharide (LPS)-induced neuroinflammation, depression, and anxiety-like behavior. METHODS: Male Sprague Dawley rats were divided into two experimental cohorts to determine the effects and the effective dose of carvacrol (whether 20 mg/kg or 50 mg/kg), and further demonstrate the mechanism of action of nuclear factor E2-related factor (Nrf2) in depression. RESULTS: We found marked neuronal alterations in the cortex and hippocampus of LPS-intoxicated animals that were associated with higher inflammatory cytokine expression such as cyclooxygenase (COX2), tumor necrosis factor-alpha (TNF-α), and c-Jun N-terminal kinase (p-JNK). These detrimental effects exacerbated oxidative stress, as documented by a compromised antioxidant system due to high lipid peroxidase (LPO). Carvacrol (20 mg/kg) significantly reverted these changes by positively modulating the antioxidant gene Nrf2, a master regulator of the downstream antioxidant pathway. To further investigate the role of Nrf2, an inhibitor of Nrf2 called all-trans retinoic acid (ATRA) was used, which further exacerbated LPS toxicity with a higher oxidative and inflammatory cytokine level. To further support our notion, we performed virtual docking of carvacrol with the Nrf2-Keap1 target and the resultant drug-protein interactions validated the in vivo findings. CONCLUSION: Collectively, our findings suggest that carvacrol (20 mg/kg) could activate the endogenous master antioxidant Nrf2, which further regulates the expression of downstream antioxidants, eventually ameliorating LPS-induced neuroinflammation and neurodegeneration.