Dose-dependent efficacy of bevacizumab in recurrent glioblastoma.

BACKGROUND: Bevacizumab (BEV), at a standard dose of 10 mg/kg every 2 weeks is associated with prolonged progression-free survival (PFS) but no improvement in overall survival (OS) in recurrent glioblastoma (rGBM). Few studies have examined the potential dose-dependent efficacy of BEV. In Ontario, reimbursement for the costs of BEV varies, and as a result, our practice began to routinely use lower dose regimens. The main aim of this study was to ensure that there was no harm to patients who received the low dose protocol. METHODS: A single-center retrospective study of patients given BEV for rGBM between 2015 and 2020 was performed. Clinical and treatment data including BEV dose regimen [SD (10 mg/kg every 2 weeks) vs. LD (5 mg/kg every 2-3 weeks or 10 mg/kg every 3 weeks)] received at the time of rGBM diagnosis were captured. Overall survival (OS) and progression-free survival (PFS) on BEV were compared using the Kaplan-Meier product-limit method. Log-rank test was used to compare potential predictive factors. Cox regression model was performed for multivariable analysis of OS and PFS. RESULTS: A total of 96 patients were included with a median follow-up duration of 6.84 months (range 1.12-50.63 months) from the date of the first infusion. The LD group consisted of 55 of the 96 patients. By virtue of funding mechanisms for BEV, the median age in the LD group was significantly higher (62 vs. 54 years p = 0.009). There was no difference in MGMT status between the two groups (p = 0.60). The LD group had prolonged median PFS (5.89 months versus 3.22 months; p = 0.0112) and OS (10.23 months versus 6.28 months; p = 0.0010). Multivariable analysis including the dose of BEV, the extent of resection, gender, and age revealed that standard dose of BEV, subtotal resection, and female sex were associated with worse overall survival. Nine patients in the SD group vs. 18 patients in the LD group reported an adverse event related to BEV. CONCLUSION: For patients with recurrent GBM, we found that a low dose regimen of BEV was associated with prolonged OS and PFS compared to the standard dose regimen. Lower dose schedules may be a better and more cost-effective option for patients with rGBM. Lower costs might provide more equitable access to this very important palliative drug.

Predicting 30-day mortality after surgery for metastatic disease of the spine: the H2-FAILS score.

PURPOSE: Scoring systems for metastatic spine disease focus on predicting long- to medium-term mortality or a combination of perioperative morbidity and mortality. However, accurate prediction of perioperative mortality alone may be the most important factor when considering surgical intervention. We aimed to develop and evaluate a new tool, the H2-FAILS score, to predict 30-day mortality after surgery for metastatic spine disease. METHODS: Using the National Surgical Quality Improvement Program database, we identified 1195 adults who underwent surgery for metastatic spine disease from 2010 to 2018. Incidence of 30-day mortality was 8.7% (n = 104). Independent predictors of 30-day mortality were used to derive the H2-FAILS score. H2-FAILS is an acronym for: Heart failure (2 points), Functional dependence, Albumin deficiency, International normalized ratio elevation, Leukocytosis, and Smoking (1 point each). Discrimination was assessed using area under the receiver operating characteristic curve (AUC). The H2-FAILS score was compared with the American Society of Anesthesiologists Physical Status Classification (ASA Class), the 5-item modified Frailty Index (mFI-5), and the New England Spinal Metastasis Score (NESMS). Internal validation was performed using bootstrapping. Alpha = 0.05. RESULTS: Predicted 30-day mortality was 1.8% for an H2-FAILS score of 0 and 78% for a score of 6. AUC of the H2-FAILS was 0.77 (95% confidence interval: 0.72-0.81), which was higher than the mFI-5 (AUC 0.58, p < 0.001), ASA Class (AUC 0.63, p < 0.001), and NESMS (AUC 0.70, p = 0.004). Internal validation showed an optimism-corrected AUC of 0.76. CONCLUSIONS: The H2-FAILS score accurately predicts 30-day mortality after surgery for spinal metastasis. LEVEL OF EVIDENCE: Prognostic level III.

Anticandidal Activity of Capsaicin and Its Effect on Ergosterol Biosynthesis and Membrane Integrity of Candida albicans.

Oral candidiasis is an infection of the oral cavity commonly caused by Candida albicans. Endodontic treatment failure has also been found to be persistent from C. albicans in the root canal system. Despite the availability of antifungal drugs, the management of Candida oral infection is difficult as it exhibits resistance to a different class of antifungal drugs. Therefore, it is necessary to discover new antifungal compounds to cure fungal infections. This study aimed to examine the antifungal susceptibility of Capsaicin, an active compound of chili pepper. The susceptibility of Capsaicin and Fluconazole was tested against the Candida species by the CLSI (M27-A3) method. The effect of Capsaicin on the fungal cell wall was examined by the ergosterol inhibitory assay and observed by the scanning electron micrograph. The MIC range of Capsaicin against Candida isolates from oral (n = 30), endodontic (n = 8), and ATCC strains (n = 2) was 12.5−50 µg/mL. The MIC range of Fluconazole (128- 4 µg/mL) significantly decreased (2- to 4-fold) after the combination with Capsaicin (MIC/4) (p < 0.05). Capsaicin (at MIC) significantly reduced the mature biofilm of C. albicans by 70 to 89% (p < 0.01). The ergosterol content of the cell wall decreased significantly with the increase in the Capsaicin dose (p < 0.01). Capsaicin showed high sensitivity against the hyphae formation and demonstrated a more than 71% reduction in mature biofilm. A fluorescence microscopy revealed the membrane disruption of Capsaicin-treated C. albicans cells, whereas a micrograph of electron microscopy showed the distorted cells' shape, ruptured cell walls, and shrinkage of cells after the release of intracellular content. The results conclude that Capsaicin had a potential antifungal activity that inhibits the ergosterol biosynthesis in the cell wall, and therefore, the cells' structure and integrity were disrupted. More importantly, Capsaicin synergistically enhanced the Fluconazole antifungal activity, and the synergistic effect might be helpful in the prevention of Fluconazole resistance development and reduced drug-dosing.

Effect of arginine supplementation on the production of milk fat in dairy cows.

Arginine, one of the conditionally essential AA, has been reported to affect fat synthesis and metabolism in nonruminant animals by influencing adenosine monophosphate activated protein kinase (AMPK) in some organs. In dairy cows, the effect of Arg on milk fat production is not clear, and any potential mechanism that underlies the effect is unknown. We tested the hypothesis that Arg infusion would improve the production of milk fat, and explored possible mechanism that might underlie any effect. We used 6 healthy lactating cows at 20 ± 2 d in milk, in fourth parity, with a body weight of 508 ± 14 kg, body condition score of 3.0 ± 0, and a milk yield of 30.6 ± 1.8 kg/d (mean ± standard deviation). The cows were blocked by days in milk and milk yield and each cow received 3 treatments in a replicated 3 × 3 Latin square design, with each of the experimental periods lasting 7 d with a 14-d washout between each period. The treatments, delivered in random order, were (1) infusion of saline (control); (2) infusion of 0.216 mol/d of l-Arg in saline (Arg); (3) infusion of 0.868 mol/d of l-Ala in saline (the Arg and Ala treatments were iso-nitrogenous) through a jugular vein. On the last day of each experimental period, blood was sampled to measure insulin, nitric oxide, glucose, and nonesterified fatty acid, and the liver and mammary gland were biopsied to measure the expression of genes. Milk yield was recorded, and milk fat percentage was measured daily during each of the experimental periods. The yield and composition of fatty acid (FA) in milk was measured daily on the last 3 d during each of the experimental periods. The data were analyzed using a mixed model with treatment as a fixed factor, and cow, period, and block as random factors. The daily milk yield and milk fat yield when the cows were infused with Arg were 2.2 kg and 76 g, respectively, higher than that in control, and 1.8 kg and 111 g, respectively, higher than that in Ala. When the cows were infused with Arg they had higher concentration and yield of de novo synthesized FA, than when they received the control or Ala infusions, although milk fat percentage, daily feed intake, and the digestibility of nutrients were not affected by treatment. The serum concentration of nitric oxide and insulin were higher during Arg than during control or Ala, with no difference between control and Ala. In the liver, the expression of the genes coding for AMPK (PRKAA1, PRKAB1, and PRKAG1) and genes related to the oxidation of FA were higher during Arg than during control or Ala, whereas in the mammary gland the expression PRKAB1 was lowest, and the expression of genes involved in the synthesis of milk fat were highest, during Arg infusion. The results suggest the intravenous infusion of Arg enhanced the production of milk fat by promoting the de novo synthesis of FA and increasing milk yield.

Adjuvant radiotherapy improves overall survival when added to surgery and chemotherapy for uterine carcinosarcoma: a surveillance, epidemiology, and end results analysis.

BACKGROUND: Uterine carcinosarcoma (UCS) confers a high recurrence risk following surgery, and adjuvant chemotherapy (CHT) is typically administered in all stages. The benefit of radiation therapy (RT) in UCS, when added to adjuvant CHT, is unknown. We sought to analyze the Surveillance, Epidemiology, and End Results (SEER) database to ascertain whether RT improves overall survival (OS) when added to surgery and CHT for UCS. METHODS: SEER 18 Custom Data registries (Nov 2018 submission) were queried for uterine (ICD10 C54.1-9, C55.9) carcinosarcoma (ICD-0-3 8980-3). Patients with stage I-III UCS who underwent surgery and CHT ± RT were analyzed with univariate analysis (UVA) and multivariable analysis (MVA) using Kaplan-Meier and Cox proportional hazards regression modeling. Propensity-score matched analysis with inverse probability of treatment weighting (IPTW) was performed to account for indication bias. Furthermore, conditional landmark analysis (minimum three-month follow-up) was performed to minimize immortal time bias. RESULTS: All 1541 patients (1988-2016) underwent surgery and CHT and 54% received RT. On UVA, RT improved median and 5-year OS from 41 to 87 months and 43-55%, respectively (HR 0.65, 95% CI 0.56-0.77) (p < 0.001). After IPTW adjustment, RT improved median and 5-year OS from 46 to 65 months and 46-53%, respectively (HR 0.74, 95% CI 0.63-0.87) (p < 0.001). The benefit of RT remained on unadjusted and adjusted MVA and conditional landmark analysis. CONCLUSION: In stage I-III UCS treated with surgery and CHT, receipt of RT is associated with OS benefit. Further prospective data are needed to investigate the RT's benefit in UCS.

'The Violet Killer'-Successful Treatment of an Infant with Chromobacterium violaceum Sepsis.

Chromobacterium violaceum, a facultative anaerobic proteobacterium, is isolated from water and soil in tropical areas and has been implicated in infections like septicemia, visceral abscesses, skin and soft tissue infections, meningitis and diarrhea. Chromobacterium violaceum sepsis, a rarely reported phenomenon has a very high mortality rate. Here, we report a unique case of Chromobacterium sepsis in an infant. A 48-day-old baby boy was referred to our institution with h/o fever, loose stools and reduced activity. He was intubated and referred to us in septic shock. Radiological investigations revealed multiple abscesses in the liver, spleen and kidneys. The infant was successfully treated with trimethoprim-sulfamethoxazole and ciprofloxacin.

Does thrombolysis for pulmonary embolism reduce the risk of chronic complications?

We assessed the efficacy of thrombolysis in avoiding long-term complications. Notes of patients thrombolysed for PE in the 2-year period were reviewed. The initial CTPA and echocardiogram results before thrombolysis were compared to the results of follow up imaging repeated after 6 months. Twenty-two patients were thrombolysed for PE. 14 patients had sub-massive PE and 8 patients had massive PE. The right ventricle (RV) was dilated on pre-thrombolysis echocardiogram in 16 patients. On follow up echocardiography all patients with massive PE (6 studies) had a normal RV size, with pulmonary artery pressures (PAP) of 29mmHg. Follow up echocardiography of patients with submassive PE (13 studies) showed 11 patients with a normal RV, with PAP of 28 mmHg.

A Nationwide, Systematic, and Comprehensive Assessment of Surgical Capacity in Lebanon: Results of the Surgical Capacity in Areas With Refugees (SCAR) Study.

OBJECTIVE: We sought to perform a systematic, comprehensive, and nationwide cross-sectional analysis of surgical capacity in Lebanon. BACKGROUND: Providing surgical care in refugee areas is increasingly recognized as a global health priority. The surgical capacity of Lebanon where at least 1 in 6 inhabitants is currently a refugee remains unknown. METHODS: The Surgical Capacity in Areas with Refugees cross-sectional study included 3 steps: (1) geographically mapping all hospitals providing surgical care in Lebanon, (2) systematically assessing each hospital's surgical capacity, and (3) identifying surgical care gaps/disparities. First, a list of hospitals in Lebanon and their locations was generated combining data from the Lebanese Ministry of Health and Syndicate of Hospitals. Specialty, rehabilitation, and maternity facilities were excluded. Second, the validated 5 domain Personnel, Infrastructure, Procedures, Equipment, and Supplies (PIPES) tool was administered in each hospital through a face-to-face or phone interview. Hospitals' PIPES indices were computed; data were aggregated and analyzed for geographic and private/public disparities. RESULTS: A total of 129 hospitals were geographically mapped; 20% were public. The PIPES tool was administered in all hospitals (100%). The mean PIPES index was 10.98 (Personnel = 14.91, Infrastructure = 15.36, Procedures = 37.47, Equipment = 21.63, Supplies = 24.78). The number of hospital beds, operating rooms, surgeons, and anesthesiologists per 100,000 people were 217, 8, 16, and 9, respectively. Deficiencies in infrastructure were significant, whereby 62%, 36%, 16%, and 5% of hospitals lack incinerators, pretested blood, intensive care units, and computed tomography, respectively. Continuous external electricity was lacking in 16 hospitals (12%). Compared to private hospitals, public hospitals had a lower PIPES index (10.48 vs 11.1, P = 0.022), including lower Personnel and Infrastructure scores (12.31 vs 15.57, P = 0.03; 14.04 vs 15.7, P = 0.003, respectively). Geographically, the administrative governorates with highest refugee concentrations had the lowest PIPES indices. CONCLUSIONS: Evaluating surgical capacity in Lebanon reveals significant deficiencies, most pronounced in public hospitals in which refugee care is provided and in areas with the highest refugee concentration.

Refugee Access to Surgical Care in Lebanon: A Post Hoc Analysis of the SCAR Study.

BACKGROUND: Lebanon hosts an estimated one million Syrian refugees registered with the United Nations High Commissioner for Refugees (UNHCR). The UNHCR contracts with select Lebanese hospitals to provide affordable primary and emergency care to refugees. We aimed to assess the surgical capabilities of UNHCR-affiliated hospitals in Lebanon. METHODS: Cross-sectional data from the Surgical Capacity in Areas with Refugees study were combined with hospital affiliation data obtained from the UNHCR. The Surgical Capacity in Areas with Refugees study evaluated surgical capacity in Lebanon by mapping all acute care hospitals and administering the five domain Personnel, Infrastructure, Procedures, Equipment, and Supplies (PIPES) tool to each hospital. Mean PIPES indices and mean numbers of hospital beds, surgeons, and anesthesiologists were compared between UNHCR-affiliated and nonaffiliated hospitals. Geographically, the distribution of UNHCR-affiliated hospitals was cross-referenced with refugee population distributions. RESULTS: One hundred and twenty nine hospitals were included, 35 (27.1%) of which were affiliated with the UNHCR. The PIPES tool was administered across all hospitals. Mean PIPES indices and mean number of hospital beds, general surgeons, and anesthesiologists were similar between UNHCR-affiliated and nonaffiliated hospitals. Geographical mapping of hospitals and refugee populations across Lebanon revealed a disparity in the Northeastern region of the country: that region had the highest number of refugees but lacked sufficient UNHCR coverage. CONCLUSIONS: Hospitals covered by the UNHCR performed similarly to nonaffiliated hospitals with respect to all aspects of the PIPES surgical capacity tool. However, there is a concerning geographic mismatch between UNHCR coverage and refugee density, specifically in the governorates of Akkar, Bekaa, and Baalbek-Hermel.

Reasons for Opioid Discontinuation and Unintended Consequences Following Opioid Discontinuation Within the TOPCARE Trial.

OBJECTIVE: To identify reasons for opioid discontinuation and post-discontinuation outcomes among patients in the Transforming Opioid Prescribing in Primary Care (TOPCARE) study. DESIGN: In TOPCARE, an intervention to improve adherence to opioid prescribing guidelines, randomized intervention primary care providers (PCPs) received nurse care manager support, an electronic registry, academic detailing, and electronic tools, and control PCPs received electronic tools only. SETTING: Four Boston safety net primary care practices. SUBJECTS: Patients in both TOPCARE study arms who discontinued opioid therapy during the trial. METHODS: Through chart review, we examined the reason for discontinuation and post-discontinuation outcomes: one or more PCP visits, one or more pain-related emergency department (ED) visits, evidence of opioid use disorder (OUD), and referral for OUD treatment. RESULTS: Opioid discontinuations occurred in 83/586 (14.2%) intervention and 42/399 (10.5%) control patients (P = 0.09). Among patients who discontinued opioids, 81 (65%) discontinued for misuse, with no difference by group (P = 0.38). Aberrancy in monitoring (e.g., discordant urine drug test results) was the most common type of misuse prompting discontinuation (occurring in (51/83 [61%] of intervention patients vs 19/42 [45%, P = 0.08] of control patients). Intervention patients who discontinued opioids had less PCP follow-up (65% vs 88%, P < 0.01) compared with control patients. We found no differences between groups for pain-related ED visits, evidence of OUD, or OUD treatment referral following discontinuation. CONCLUSIONS: The decreased follow-up among TOPCARE intervention patients who discontinued opioids highlights the need to understand unintended consequences of involuntary opioid discontinuations resulting from interventions to reduce opioid risk.

Minimally invasive transforaminal lumbar interbody fusion with expandable versus static interbody devices: radiographic assessment of sagittal segmental and pelvic parameters.

OBJECTIVE Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has been adopted as an alternative technique to hasten recovery and minimize postoperative morbidity. Advances in instrumentation technologies and operative techniques have evolved to maximize patient outcomes as well as radiographic results. The development of expandable interbody devices allows a surgeon to perform MIS-TLIF with minimal tissue disruption. However, sagittal segmental and pelvic radiographic outcomes after MIS-TLIF with expandable interbody devices are not well characterized. The object of this study is to evaluate the radiographic sagittal lumbar segmental and pelvic parameter outcomes of MIS-TLIF performed using an expandable interbody device. METHODS A retrospective review of MIS-TLIFs performed between 2014 and 2016 at a high-volume center was performed. Radiographic measurements were performed on lateral radiographs before and after MIS-TLIF with static or expandable interbody devices. Radiographic measurements included disc height, foraminal height, fused disc angle, lumbar lordosis, pelvic incidence, sacral slope, and pelvic tilt. Mismatch between pelvic incidence and lumbar lordosis were calculated for each radiograph. RESULTS A total of 48 MIS-TLIFs were performed, predominantly at the L4-5 level, in 44 patients. MIS-TLIF with an expandable interbody device led to a greater and more sustained increase in disc height when compared with static interbody devices. Foraminal height increased after MIS-TLIF with expandable but not with static interbody devices. MIS-TLIF with expandable interbody devices increased index-level segmental lordosis more than with static interbody devices. The increase in segmental lordosis was sustained in the patients with expandable interbody devices but not in patients with static interbody devices. For patients with a collapsed disc space, MIS-TLIF with an expandable interbody device provided superior and longer-lasting increases in disc height, foraminal height, and index-level segmental lordosis than in comparison with patients with static interbody devices. Using an expandable interbody device improved the Oswestry Disability Index scores more than using a static interbody device, and both disc height and segmental lordosis were correlated with improved clinical outcome. Lumbar MIS-TLIF with expandable or static interbody devices had no effect on overall lumbar lordosis, pelvic parameters, or pelvic incidence-lumbar lordosis mismatch. CONCLUSIONS Performing MIS-TLIF with an expandable interbody device led to a greater and longer-lasting restoration of disc height, foraminal height, and index-level segmental lordosis than MIS-TLIF with a static interbody device, especially for patients with a collapsed disc space. However, neither technique had any effect on radiographic pelvic parameters.

Waterpipe tobacco smoking prevalence and illegal underage use in waterpipe-serving premises: a cross-sectional analysis among schoolchildren in Stoke-on-Trent.

OBJECTIVES: Waterpipe tobacco smoking has received little epidemiological and policy attention in the UK despite reports of increasing prevalence alongside an anecdotally non-compliant industry. This study aimed to determine how waterpipe tobacco smoking is changing among young people in the UK, both in terms of prevalence and sociodemographic correlates of use, and to quantify the extent of illegal underage use in waterpipe-serving premises in the UK. STUDY DESIGN: Repeat cross-sectional. METHODS: A secondary analysis of two cross-sectional surveys (total N = 3376), conducted in 2013 and 2015 among secondary school students aged 11-16 years in Stoke-on-Trent, measured lifetime (both surveys) and regular (at least monthly; 2015 survey only) waterpipe tobacco prevalence and location of usual use. Logistic regression models measured the association between independent variables (age, sex, ethnicity, presence of free school meals, cigarette smoking status) with lifetime and regular waterpipe tobacco use, and with illegal underage use; the latter defined as usually smoking waterpipe tobacco in a waterpipe-serving premise. RESULTS: Lifetime waterpipe tobacco prevalence remained similar in 2013 (13.7%, 95% confidence interval [CI] 12.0-15.4%) and 2015 (14.6%, 95% CI 12.8-16.4%), whereas regular use was measured at 2.9% (95% CI 2.1-3.8%) in 2015. Older, non-white, males who concurrently used cigarettes had higher odds of lifetime waterpipe tobacco use. Illegal underage use was reported among 27.1% of all regular users, correlates of which included increasing age and South Asian ethnicity. The presence of free school meals was not associated with lifetime or regular waterpipe tobacco prevalence, nor illegal underage use. CONCLUSIONS: Increased monitoring of waterpipe tobacco prevalence and patterns, including the underage policy compliance of waterpipe-serving premises, is needed to help inform policy decisions to control waterpipe tobacco use.

Universality class of the mott transition.

Pressure dependence of the conductivity and thermoelectric power is measured through the Mott transition in the layer organic conductor EtMe_{3}P[Pd(dmit)_{2}]_{2}. The critical behavior of the thermoelectric effect provides a clear and objective determination of the Mott-Hubbard transition during the isothermal pressure sweep. Above the critical end point, the metal-insulator crossing, determined by the thermoelectric effect minimum value, is not found to coincide with the maximum of the derivative of the conductivity as a function of pressure. We show that the critical exponents of the Mott-Hubbard transition fall within the Ising universality class regardless of the dimensionality of the system.

Parental smoking and exposure to environmental tobacco smoke are associated with waterpipe smoking among youth: results from a national survey in Lebanon.

OBJECTIVES: Waterpipe tobacco smoking (WTS) is a growing public health concern worldwide yet little is known about the epidemiology of use among young people. The objectives of this study were to examine the prevalence, patterns and correlates of WTS among students across Lebanon. STUDY DESIGN: The study design was a cross sectional survey. METHODS: 126-item tobacco questionnaire was conducted among 1128 sixth and seventh grade students across Lebanon. Current patterns of use were descriptively analysed, and logistic regression models examined correlates of WTS. RESULTS: Ever WTS prevalence was 44.3%, current WTS prevalence was triple that of cigarettes (22.1% vs 7.4%), and 40.0% of current users were at least weekly or daily smokers. Initiation and patterns of use, as well as addiction and cessation attitudes have been reported. Significant correlates of current WTS included older age, reduced religiosity, peer and parent tobacco use, recent waterpipe advertisement exposure, increased pluralistic ignorance and current cigarette use. Significant correlates of ever WTS were similar to current WTS, but included second hand waterpipe tobacco smoke exposure at home and did not include recent waterpipe advertisement exposure. Neither gender nor socio-economic status were significant correlates of current or ever WTS. CONCLUSIONS: Waterpipe is the most common form of tobacco smoking, and is used regularly, among sixth and seventh grade Lebanese students. It should be considered a public health priority with increased tobacco surveillance and legislation. Widespread educational and policy interventions might help denormalize the social acceptability of WTS. Meanwhile, more research is needed to understand the changing paradigm of WTS epidemiology and the health outcomes among young smokers.

Power spectrum: A detailed dataset on electric demand and environmental interplays.

This dataset provides detailed electricity demand forecasting metrics for the Sharjah Electricity and Water Authority (SEWA) over 2020 and 2021. Data encompasses both hourly and daily demand patterns, enriched with specific environmental parameters such as temperature, humidity, and solar irradiance. Additionally, SEWA's unique load metrics and lagged demand values, representing previous hour demand, are included. Data was procured using advanced electrical load meters and standardized weather data acquisition systems. Preliminary and advanced data processing was conducted via Excel tool. This comprehensive dataset is invaluable for stakeholders in electricity provisioning and policy-making. Its granular detail makes it a pivotal resource for modelling and forecasting electricity demand, aiding in infrastructure planning, renewable energy considerations, and demand-side management. The potential applications span across academic, policy, and industry domains, rendering it a versatile tool for future electricity demand research.

Palbociclib and Fulvestrant Combined Regimen Induced Prolonged Bone Metastasis Control of Stage IV HR+/HER2- Breast Cancer: A Case Report.

The management of advanced metastasized breast cancer (BC) is a clinically challenging entity with a wide spectrum of novel therapeutics being introduced to the market. Such agents have remodeled BC treatment landscape and prolonged patients' survival. Over the past decade, a growing body of literature has shed lights on CDK4/6 involvement in oncogenesis and the role of its inhibitors in clinical use with palbociclib being the prototype drug. We present a case of a 58-year-old post-menopausal Middle-Eastern woman diagnosed with stage IV HR+/HER2- breast cancer with extensive bone metastasis. The lesions were widely distributed across the axial skeleton including base of the skull, sternum, ribs, left iliac bone, right inferior pubic ramus, cervical, thoracic, and lumbosacral vertebrae. The patient was started on therapeutic doses of letrozole and zoledronic acid in conjunction with adjuvant radiotherapy. A significant partial response was achieved reaching 70% remission followed by sternum disease progression. A decision was made to switch letrozole for tamoxifen which resulted in disease stability. Due to postmenopausal bleeding, tamoxifen was held and letrozole was reintroduced leading to regimen failure and disease advancement. Palbociclib and fulvestrant were started accordingly, yielding a remarkable metabolic response of all bone metastatic lesions (stable disease) after three months of the regimen initiation. The aforementioned stable disease status continued for approximately three years up to this point.

Initial institutional experience using a robotic arm-enabled 4K 3D exoscope in neurosurgical operations.

The extracorporeal telescope (exoscope) presents a novel digital camera system as a versatile alternative to traditional optical microscopy for microsurgery and minimally invasive neurosurgical operations. Recent innovations in exoscope technology offer 4K-definition multiscreen outputs, pneumatic robot arms, 3-dimensional depth perception, and greater illumination, focus, and magnification powers for enhanced intraoperative visualization. The authors present their initial institutional experience using a robotic arm-enabled 4K 3D exoscope in a variety of cranial and spinal neurosurgical operations, namely Chiari decompression, microvascular decompression for trigeminal neuralgia, anterior cervical discectomy, and lumbar decompressions. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23150.

Novel Ameloblastin Variants, Contrasting Amelogenesis Imperfecta Phenotypes.

Amelogenesis imperfecta (AI) comprises a group of rare, inherited disorders with abnormal enamel formation. Ameloblastin (AMBN), the second most abundant enamel matrix protein (EMP), plays a critical role in amelogenesis. Pathogenic biallelic loss-of-function AMBN variants are known to cause recessive hypoplastic AI. A report of a family with dominant hypoplastic AI attributed to AMBN missense change p.Pro357Ser, together with data from animal models, suggests that the consequences of AMBN variants in human AI remain incompletely characterized. Here we describe 5 new pathogenic AMBN variants in 11 individuals with AI. These fall within 3 groups by phenotype. Group 1, consisting of 6 families biallelic for combinations of 4 different variants, have yellow hypoplastic AI with poor-quality enamel, consistent with previous reports. Group 2, with 2 families, appears monoallelic for a variant shared with group 1 and has hypomaturation AI of near-normal enamel volume with pitting. Group 3 includes 3 families, all monoallelic for a fifth variant, which are affected by white hypoplastic AI with a thin intact enamel layer. Three variants, c.209C>G; p.(Ser70*) (groups 1 and 2), c.295T>C; p.(Tyr99His) (group 1), and c.76G>A; p.(Ala26Thr) (group 3) were identified in multiple families. Long-read AMBN locus sequencing revealed these variants are on the same conserved haplotype, implying they originate from a common ancestor. Data presented therefore provide further support for possible dominant as well as recessive inheritance for AMBN-related AI and for multiple contrasting phenotypes. In conclusion, our findings suggest pathogenic AMBN variants have a more complex impact on human AI than previously reported.

Impact of Upper Limb Motor Recovery on Functional Independence After Traumatic Low Cervical Spinal Cord Injury.

Cervical spinal cord injury (SCI) causes devastating loss of upper limb function and independence. Restoration of upper limb function can have a profound impact on independence and quality of life. In low-cervical SCI (level C5-C8), upper limb function can be restored via reinnervation strategies such as nerve transfer surgery. The translation of recovered upper limb motor function into functional independence in activities of daily living (ADLs), however, remains unknown in low cervical SCI (i.e., tetraplegia). The objective of this study was to evaluate the association of patterns in upper limb motor recovery with functional independence in ADLs. This will then inform prioritization of reinnervation strategies focused to maximize function in patients with tetraplegia. This retrospective study performed a secondary analysis of patients with low cervical (C5-C8) enrolled in the SCI Model Systems (SCIMS) database. Baseline neurological examinations and their association with functional independence in major ADLs-i.e., eating, bladder management, and transfers (bed/wheelchair/chair)-were evaluated. Motor functional recovery was defined as achieving motor strength, in modified research council (MRC) grade, of ≥ 3 /5 at one year from ≤ 2/5 at baseline. The association of motor function recovery with functional independence at one-year follow-up was compared in patients with recovered elbow flexion (C5), wrist extension (C6), elbow extension (C7), and finger flexion (C8). A multi-variable logistic regression analysis, adjusting for known factors influencing recovery after SCI, was performed to evaluate the impact of motor function at one year on a composite outcome of functional independence in major ADLs. Composite outcome was defined as functional independence measure score of 6 or higher (complete independence) in at least two domains among eating, bladder management, and transfers. Between 1992 and 2016, 1090 patients with low cervical SCI and complete neurological/functional measures were included. At baseline, 67% of patients had complete SCI and 33% had incomplete SCI. The majority of patients were dependent in eating, bladder management, and transfers. At one-year follow-up, the largest proportion of patients who recovered motor function in finger flexion (C8) and elbow extension (C7) gained independence in eating, bladder management, and transfers. In multi-variable analysis, patients who had recovered finger flexion (C8) or elbow extension (C7) had higher odds of gaining independence in a composite of major ADLs (odds ratio [OR] = 3.13 and OR = 2.87, respectively, p < 0.001). Age 60 years (OR = 0.44, p = 0.01), and complete SCI (OR = 0.43, p = 0.002) were associated with reduced odds of gaining independence in ADLs. After cervical SCI, finger flexion (C8) and elbow extension (C7) recovery translate into greater independence in eating, bladder management, and transfers. These results can be used to design individualized reinnervation plans to reanimate upper limb function and maximize independence in patients with low cervical SCI.

Time trends of gender-based differences in lipid goal attainments during secondary prevention of coronary artery disease: results of a 5-year survey.

Coronary artery disease is the leading cause of death in both men and women worldwide. Little is known about gender-based differences in lipid goal attainment during secondary prevention of coronary artery disease. We conducted this study to analyze gender differences in low-density lipoprotein cholesterol target attainment in secondary prevention after acute myocardial infarction over a 5-year period. In this retrospective study, the electronic database of lipid clinic at a single center was used as the data source. Temporal trends and gender differences in demographics, lipid profile, and medication use were determined. Goal low-density lipoprotein (LDL) was defined per National Cholesterol Education Program ATP III guidelines.A total of 1365 patients (823 males, 542 females) constituted the study sample. Patients in 2007 were older than those in 2003 (females 68.6 ± 14 vs. 70.7 ± 11.7 years; males 63.6 ± 12 vs. 65.8 ± 11 years; P < 0.05) and had a higher body mass index (females 27.8 ± 1 vs. 28.6 ± 1 kg/m; males 27.6 ± 1 vs. 28.1 ± 1 kg/m, in 2003 and 2007 respectively, P < 0.05). Mean LDL decreased significantly overtime in both males and females. No gender difference in lipid-lowering therapy was observed. Females had a higher LDL than did males in 2003 (115.3 ± 12.3 vs. 99.7 ± 12.5 mg/dL; P < 0.05), and this difference persisted through 2007 (102.2 ± 11.7 vs. 91.3 ± 11.2 mg/dL; P < 0.05). Overall rate of achieving goal LDL improved from 76.5% (2003) to 83.02% (2007), P < 0.05, but remained lower for females than for males both in 2003 and 2007 [69.8% vs. 80.1% (2003), P < 0.05, and 77.9% vs. 85.6% (2007), P < 0.05].The trend over a recent 5-year period shows that females are less likely to achieve goal LDL than males are, and it indicates the need for more aggressive lipid-lowering strategies in females.