Association between the LRP1B and APOE loci and the development of Parkinson's disease dementia.

Parkinson's disease is one of the most common age-related neurodegenerative disorders. Although predominantly a motor disorder, cognitive impairment and dementia are important features of Parkinson's disease, particularly in the later stages of the disease. However, the rate of cognitive decline varies among Parkinson's disease patients, and the genetic basis for this heterogeneity is incompletely understood. To explore the genetic factors associated with rate of progression to Parkinson's disease dementia, we performed a genome-wide survival meta-analysis of 3923 clinically diagnosed Parkinson's disease cases of European ancestry from four longitudinal cohorts. In total, 6.7% of individuals with Parkinson's disease developed dementia during study follow-up, on average 4.4 ± 2.4 years from disease diagnosis. We have identified the APOE ε4 allele as a major risk factor for the conversion to Parkinson's disease dementia [hazard ratio = 2.41 (1.94-3.00), P = 2.32 × 10-15], as well as a new locus within the ApoE and APP receptor LRP1B gene [hazard ratio = 3.23 (2.17-4.81), P = 7.07 × 10-09]. In a candidate gene analysis, GBA variants were also identified to be associated with higher risk of progression to dementia [hazard ratio = 2.02 (1.21-3.32), P = 0.007]. CSF biomarker analysis also implicated the amyloid pathway in Parkinson's disease dementia, with significantly reduced levels of amyloid ß42 (P = 0.0012) in Parkinson's disease dementia compared to Parkinson's disease without dementia. These results identify a new candidate gene associated with faster conversion to dementia in Parkinson's disease and suggest that amyloid-targeting therapy may have a role in preventing Parkinson's disease dementia.

A novel cognitive neurosurgery approach for supramaximal resection of non-dominant precuneal gliomas: a case report.

Despite mounting evidence pointing to the contrary, classical neurosurgery presumes many cerebral regions are non-eloquent, and therefore, their excision is possible and safe. This is the case of the precuneus and posterior cingulate, two interacting hubs engaged during various cognitive functions, including reflective self-awareness; visuospatial and sensorimotor processing; and processing social cues. This inseparable duo ensures the cortico-subcortical connectivity that underlies these processes. An adult presenting a right precuneal low-grade glioma invading the posterior cingulum underwent awake craniotomy with direct electrical stimulation (DES). A supramaximal resection was achieved after locating the superior longitudinal fasciculus II. During surgery, we found sites of positive stimulation for line bisection and mentalizing tests that enabled the identification of surgical corridors and boundaries for lesion resection. When post-processing the intraoperative recordings, we further identified areas that positively responded to DES during the trail-making and mentalizing tests. In addition, a clear worsening of the patient's self-assessment ability was observed throughout the surgery. An awake cognitive neurosurgery approach allowed supramaximal resection by reaching the cortico-subcortical functional limits. The mapping of complex functions such as social cognition and self-awareness is key to preserving patients' postoperative cognitive health by maximizing the ability to resect the lesion and surrounding areas.

A Distributed Approach for Estimating Battery State-Of-Charge in Solar Farms.

A common problem in solar farms is to predict when accumulators stop working optimally and start losing efficiency. This paper proposes and describes how to use Bayesian networks together with expert systems to predict this moment by using a telecontrol multiagent system for monitoring solar farms with distributed sensors, which was developed in a previous work. To this end, a Bayesian network model and its implementation are proposed. The resulting system meets the requirements of telecontrol systems (reliability, flexibility, and response time), yields a solution for the prediction of lifespan batteries, and provides the multiagent system with autonomous intelligent capabilities and integrated learning.

Improving Classification Algorithms by Considering Score Series in Wireless Acoustic Sensor Networks.

The reduction in size, power consumption and price of many sensor devices has enabled the deployment of many sensor networks that can be used to monitor and control several aspects of various habitats. More specifically, the analysis of sounds has attracted a huge interest in urban and wildlife environments where the classification of the different signals has become a major issue. Various algorithms have been described for this purpose, a number of which frame the sound and classify these frames, while others take advantage of the sequential information embedded in a sound signal. In the paper, a new algorithm is proposed that, while maintaining the frame-classification advantages, adds a new phase that considers and classifies the score series derived after frame labelling. These score series are represented using cepstral coefficients and classified using standard machine-learning classifiers. The proposed algorithm has been applied to a dataset of anuran calls and its results compared to the performance obtained in previous experiments on sensor networks. The main outcome of our research is that the consideration of score series strongly outperforms other algorithms and attains outstanding performance despite the noisy background commonly encountered in this kind of application.

Optimal Representation of Anuran Call Spectrum in Environmental Monitoring Systems Using Wireless Sensor Networks.

The analysis and classification of the sounds produced by certain animal species, notably anurans, have revealed these amphibians to be a potentially strong indicator of temperature fluctuations and therefore of the existence of climate change. Environmental monitoring systems using Wireless Sensor Networks are therefore of interest to obtain indicators of global warming. For the automatic classification of the sounds recorded on such systems, the proper representation of the sound spectrum is essential since it contains the information required for cataloguing anuran calls. The present paper focuses on this process of feature extraction by exploring three alternatives: the standardized MPEG-7, the Filter Bank Energy (FBE), and the Mel Frequency Cepstral Coefficients (MFCC). Moreover, various values for every option in the extraction of spectrum features have been considered. Throughout the paper, it is shown that representing the frame spectrum with pure FBE offers slightly worse results than using the MPEG-7 features. This performance can easily be increased, however, by rescaling the FBE in a double dimension: vertically, by taking the logarithm of the energies; and, horizontally, by applying mel scaling in the filter banks. On the other hand, representing the spectrum in the cepstral domain, as in MFCC, has shown additional marginal improvements in classification performance.

Salvia officinalis L. Essential Oils from Spain: Determination of Composition, Antioxidant Capacity, Antienzymatic, and Antimicrobial Bioactivities.

Four essential oils (EOs) from Salvia officinalis L. cultivated in Spain (Murcia Province) were analyzed by gas chromatography coupled with mass spectrometry (GC/MS) to determine their relative and absolute compositions. The main components were α-thujone (22.8 - 41.7%), camphor (10.7 - 19.8%), 1,8-cineole (4.7 - 15.6%), and ß-thujone (6.1 - 15.6%). Enantioselective gas chromatography identified (-)-α-thujone and (+)-camphor as the main enantiomers in all the analyzed EOs. Furthermore, when the EOs were tested to determine their antioxidant activity against free radicals and as ferric reducing and ferrous chelating agents, all were seen to have moderate activity due to the compounds they contained, such as linalool or terpinene. Because of their known relation with inflammatory illnesses and Alzheimer's disease, respectively, the inhibition of lipoxygenase and acetylcholinesterase was studied using the EOs. Some individual compounds also inhibited these enzymes. In addition, the studied EOs were able to inhibit the growth of Escherichia coli, Staphylococcus aureus, and Candida albicans. The characterization carried out increases our awareness of the possible uses of S. officinalis EO as natural additives in food, cosmetics, and pharmaceuticals.

Analyzing Dental Implant Sites From Cone Beam Computed Tomography Scans on a Tablet Computer: A Comparative Study Between iPad and 3 Display Systems.

PURPOSE: The aim of this study was to compare a medical-grade PACS (picture archiving and communication system) monitor, a consumer-grade monitor, a laptop computer, and a tablet computer for linear measurements of height and width for specific implant sites in the posterior maxilla and mandible, along with visualization of the associated anatomical structures. MATERIAL AND METHODS: Cone beam computed tomography (CBCT) scans were evaluated. The images were reviewed using PACS-LCD monitor, consumer-grade LCD monitor using CB-Works software, a 13″ MacBook Pro, and an iPad 4 using OsiriX DICOM reader software. The operators had to identify anatomical structures in each display using a 2-point scale. User experience between PACS and iPad was also evaluated by means of a questionnaire. RESULTS: The measurements were very similar for each device. P-values were all greater than 0.05, indicating no significant difference between the monitors for each measurement. The intraoperator reliability was very high. The user experience was similar in each category with the most significant difference regarding the portability where the PACS display received the lowest score and the iPad received the highest score. CONCLUSIONS: The iPad with retina display was comparable with the medical-grade monitor, producing similar measurements and image visualization, and thus providing an inexpensive, portable, and reliable screen to analyze CBCT images in the operating room during the implant surgery.

Composition and Antioxidant, Antienzymatic and Antimicrobial Activities of Volatile Molecules from Spanish Salvia lavandulifolia (Vahl) Essential Oils.

The current study describes the composition of Salvia lavandulifolia (Vahl) essential oils (SlEOs) obtained from plants cultivated in Murcia (Spain), as determined by gas chromatography. Relative and absolute concentrations, the enantiomeric ratios of chiral compounds and the in vitro antioxidant, antienzymatic and antimicrobial activities are described. The main components of the SlEOs were camphor, 1,8-cineole, camphene and α-pinene, and the main enantiomers were (+)-camphor and (-)-camphene. The activities against free radicals and the capacity to reduce and chelate metallic ions were measured. SlEO-3 showed the highest activity in ORAC, DPPH, ABTS and reducing power methods, while SlEO-1 exhibited the highest chelating power. The activity of lipoxygenase and acetylcholinesterase could be inhibited by all the SlEOs, being bornyl acetate and limonene the most active individual compounds against lipoxygenase and 1,8-cineole against acetylcholinesterase. SlEOs and some individual compounds inhibited Escherichia coli, Staphylococcus aureus and Candida albicans. These results increase our knowledge of SlEOs and, particularly, provide for the first time a complete characterization of SlEOs from Murcia, Spain, while proposing possible biotechnological uses for them.

Lavandula angustifolia and Lavandula latifolia Essential Oils from Spain: Aromatic Profile and Bioactivities.

Compositions of true lavender (Lavandula angustifolia) and spike lavender (Lavandula latifolia) essential oils, cultivated and extracted in the Southeast of Spain, were determined by gas chromatography coupled with mass spectrometry detection, obtaining both relative (peak area) and absolute (using standard curves) concentrations. Linalool (37-54 %), linalyl acetate (21-36 %) and (E)-ß-caryophyllene (1-3 %) were the most abundant components for L. angustifolia. Linalool (35-51 %), eucalyptol (26-32 %), camphor (10-18 %), α-pinene (1-2 %), α-terpineol (1-2 %) and α-bisabolene (1-2 %) were the most abundant components for L. latifolia. The characterization was completed with enantioselective gas chromatography, in which the determined main molecules were (-)-linalool, (-)-linalyl acetate and (+)-camphor. (S)-(-)-camphene, (R)-(+)-limonene, (1R, 9S)-(-)-(E)-ß-caryophyllene and (1R, 4R, 6R, 10S)-(-)-caryophyllene oxide were found in this study as the predominant enantiomers in Spanish L. angustifolia. The characterised essential oils were tested for their antioxidant activity against free radicals ABTS, DPPH, ORAC, chelating, and reducing power. Inhibitory activity on lipoxygenase was observed indicating a possible anti-inflammatory activity, mainly due to linalool, camphor, p-cymene and limonene. These results can be the starting point for a future study of the potential use of L. angustifolia and L. latifolia essential oils as natural cosmetic and natural pharmaceutical ingredients for several skin diseases.

Combined Predictive Model for Endoscopic Third Ventriculostomy Success in Adults and Children.

BACKGROUND: The selection of patients in whom endoscopic third ventriculostomy (ETV) can be effective remains poorly defined. The ETV success score (ETVSS) and the presence of bowing of the third ventricle have been identified as independent factors for predicting success, each with limitations. The objective of this study is to elaborate a combined predictive model to predict ETV success in a mixed cohort of patients. METHODS: Demographic, intraoperative, postoperative, and radiologic variables were analyzed in all ventriculostomies performed consecutively at a single institution from December 2004 to December 2022. Qualitative and quantitative measurements of preoperative, immediate, and late postoperative magnetic resonance imaging were conducted. Univariate analysis and logistic regression models were performed. RESULTS: 118 ETVs were performed in the selected period. Of these procedures, 106 met the inclusion criteria. The overall success rate was 71.7%, with a median follow-up of 3.64 years (interquartile range, 1.06-5.62). The median age was 36.1 years (interquartile range, 11.7-53.5). 35.84% were children (median, 7.81 years). Among the 80 patients with third ventricle bowing, the success rate was 88.8% (P < 0.001). Larger third ventricle dimensions on preoperative mid-sagittal magnetic resonance imaging were associated with increased ETV success. The model with the best receiver operating characteristic curves, with an area under the curve of 0.918 (95% confidence interval, 0.856-0.979) includes sex, ETVSS, presence of complications, and third ventricle bowing. CONCLUSIONS: The presence of bowing of the third ventricle is strongly associated with a higher ETV success rate. However, a combined predictive model that integrates it with the ETVSS is the most appropriate approach for selecting patients for ETV.

Investigation of the genetic aetiology of Lewy body diseases with and without dementia.

Up to 80% of Parkinson's disease patients develop dementia, but time to dementia varies widely from motor symptom onset. Dementia with Lewy bodies presents with clinical features similar to Parkinson's disease dementia, but cognitive impairment precedes or coincides with motor onset. It remains controversial whether dementia with Lewy bodies and Parkinson's disease dementia are distinct conditions or represent part of a disease spectrum. The biological mechanisms underlying disease heterogeneity, in particular the development of dementia, remain poorly understood, but will likely be the key to understanding disease pathways and, ultimately, therapy development. Previous genome-wide association studies in Parkinson's disease and dementia with Lewy bodies/Parkinson's disease dementia have identified risk loci differentiating patients from controls. We collated data for 7804 patients of European ancestry from Tracking Parkinson's, The Oxford Discovery Cohort, and Accelerating Medicine Partnership-Parkinson's Disease Initiative. We conducted a discrete phenotype genome-wide association study comparing Lewy body diseases with and without dementia to decode disease heterogeneity by investigating the genetic drivers of dementia in Lewy body diseases. We found that risk allele rs429358 tagging APOEe4 increases the odds of developing dementia, and that rs7668531 near the MMRN1 and SNCA-AS1 genes and an intronic variant rs17442721 tagging LRRK2 G2019S on chromosome 12 are protective against dementia. These results should be validated in autopsy-confirmed cases in future studies.

Genome-wide determinants of mortality and motor progression in Parkinson's disease.

There are 90 independent genome-wide significant genetic risk variants for Parkinson's disease (PD) but currently only five nominated loci for PD progression. The biology of PD progression is likely to be of central importance in defining mechanisms that can be used to develop new treatments. We studied 6766 PD patients, over 15,340 visits with a mean follow-up of between 4.2 and 15.7 years and carried out genome-wide survival studies for time to a motor progression endpoint, defined by reaching Hoehn and Yahr stage 3 or greater, and death (mortality). There was a robust effect of the APOE ε4 allele on mortality in PD. We also identified a locus within the TBXAS1 gene encoding thromboxane A synthase 1 associated with mortality in PD. We also report 4 independent loci associated with motor progression in or near MORN1, ASNS, PDE5A, and XPO1. Only the non-Gaucher disease causing GBA1 PD risk variant E326K, of the known PD risk variants, was associated with mortality in PD. Further work is needed to understand the links between these genomic variants and the underlying disease biology. However, these may represent new candidates for disease modification in PD.

MAPT H2 haplotype and risk of Pick's disease in the Pick's disease International Consortium: a genetic association study.

BACKGROUND: Pick's disease is a rare and predominantly sporadic form of frontotemporal dementia that is classified as a primary tauopathy. Pick's disease is pathologically defined by the presence in the frontal and temporal lobes of Pick bodies, composed of hyperphosphorylated, three-repeat tau protein, encoded by the MAPT gene. MAPT has two distinct haplotypes, H1 and H2; the MAPT H1 haplotype is the major genetic risk factor for four-repeat tauopathies (eg, progressive supranuclear palsy and corticobasal degeneration), and the MAPT H2 haplotype is protective for these disorders. The primary aim of this study was to evaluate the association of MAPT H2 with Pick's disease risk, age at onset, and disease duration. METHODS: In this genetic association study, we used data from the Pick's disease International Consortium, which we established to enable collection of data from individuals with pathologically confirmed Pick's disease worldwide. For this analysis, we collected brain samples from individuals with pathologically confirmed Pick's disease from 35 sites (brainbanks and hospitals) in North America, Europe, and Australia between Jan 1, 2020, and Jan 31, 2023. Neurologically healthy controls were recruited from the Mayo Clinic (FL, USA, or MN, USA between March 1, 1998, and Sept 1, 2019). For the primary analysis, individuals were directly genotyped for the MAPT H1-H2 haplotype-defining variant rs8070723. In a secondary analysis, we genotyped and constructed the six-variant-defined (rs1467967-rs242557-rs3785883-rs2471738-rs8070723-rs7521) MAPT H1 subhaplotypes. Associations of MAPT variants and MAPT haplotypes with Pick's disease risk, age at onset, and disease duration were examined using logistic and linear regression models; odds ratios (ORs) and ß coefficients were estimated and correspond to each additional minor allele or each additional copy of the given haplotype. FINDINGS: We obtained brain samples from 338 people with pathologically confirmed Pick's disease (205 [61%] male and 133 [39%] female; 338 [100%] White) and 1312 neurologically healthy controls (611 [47%] male and 701 [53%] female; 1312 [100%] White). The MAPT H2 haplotype was associated with increased risk of Pick's disease compared with the H1 haplotype (OR 1·35 [95% CI 1·12 to 1·64], p=0·0021). MAPT H2 was not associated with age at onset (ß -0·54 [95% CI -1·94 to 0·87], p=0·45) or disease duration (ß 0·05 [-0·06 to 0·16], p=0·35). Although not significant after correcting for multiple testing, associations were observed at p less than 0·05: with risk of Pick's disease for the H1f subhaplotype (OR 0·11 [0·01 to 0·99], p=0·049); with age at onset for H1b (ß 2·66 [0·63 to 4·70], p=0·011), H1i (ß -3·66 [-6·83 to -0·48], p=0·025), and H1u (ß -5·25 [-10·42 to -0·07], p=0·048); and with disease duration for H1x (ß -0·57 [-1·07 to -0·07], p=0·026). INTERPRETATION: The Pick's disease International Consortium provides an opportunity to do large studies to enhance our understanding of the pathobiology of Pick's disease. This study shows that, in contrast to the decreased risk of four-repeat tauopathies, the MAPT H2 haplotype is associated with an increased risk of Pick's disease in people of European ancestry. This finding could inform development of isoform-related therapeutics for tauopathies. FUNDING: Wellcome Trust, Rotha Abraham Trust, Brain Research UK, the Dolby Fund, Dementia Research Institute (Medical Research Council), US National Institutes of Health, and the Mayo Clinic Foundation.

A Proposal for a Robust Validated Weighted General Data Protection Regulation-Based Scale to Assess the Quality of Privacy Policies of Mobile Health Applications: An eDelphi Study.

BACKGROUND: Health care services are undergoing a digital transformation in which the Participatory Health Informatics field has a key role. Within this field, studies aimed to assess the quality of digital tools, including mHealth apps, are conducted. Privacy is one dimension of the quality of an mHealth app. Privacy consists of several components, including organizational, technical, and legal safeguards. Within legal safeguards, giving transparent information to the users on how their data are handled is crucial. This information is usually disclosed to users through the privacy policy document. Assessing the quality of a privacy policy is a complex task and several scales supporting this process have been proposed in the literature. However, these scales are heterogeneous and even not very objective. In our previous study, we proposed a checklist of items guiding the assessment of the quality of an mHealth app privacy policy, based on the General Data Protection Regulation. OBJECTIVE: To refine the robustness of our General Data Protection Regulation-based privacy scale to assess the quality of an mHealth app privacy policy, to identify new items, and to assign weights for every item in the scale. METHODS: A two-round modified eDelphi study was conducted involving a privacy expert panel. RESULTS: After the Delphi process, all the items in the scale were considered "important" or "very important" (4 and 5 in a 5-point Likert scale, respectively) by most of the experts. One of the original items was suggested to be reworded, while eight tentative items were suggested. Only two of them were finally added after Round 2. Eleven of the 16 items in the scale were considered "very important" (weight of 1), while the other 5 were considered "important" (weight of 0.5). CONCLUSION: The Benjumea privacy scale is a new robust tool to assess the quality of an mHealth app privacy policy, providing a deeper and complementary analysis to other scales. Also, this robust scale provides a guideline for the development of high-quality privacy policies of mHealth apps.

Heat and Moisture Exchanger Occlusion Leading to Sudden Increased Airway Pressure: A Case Report Using ChatGPT as a Personal Writing Assistant.

Heat and moisture exchangers (HMEs) are commonly used during general anesthesia to provide appropriate humidification and warming of inspired gases. While they play a critical role in mechanical ventilation, they can also lead to acute difficult ventilation if not correctly monitored and drained. We present a case of a 56-year-old female patient who underwent lower extremity vascular bypass surgery under general anesthesia and experienced sudden increased airway pressures due to occlusion of the HME caused by excessive moisture accumulation. Proper monitoring and management of the airway circuit and HMEs can help prevent complications and ensure proper ventilation during surgery. When acute difficult ventilation is encountered during general anesthesia, a systematic approach should be taken to differentiate between patient and external factors. Other differential diagnoses for acute difficult ventilation include bronchospasm, aspiration, endotracheal tube misplacement, pulmonary embolism, and tension pneumothorax. HME occlusion should be considered as part of the differential diagnosis for intraoperative hypoxia. Proactive replacement of HMEs in long cases can prevent occlusion and ensure proper ventilation.

Peripheral Nerve Stimulation for Chronic Intractable Neuropathic Pain Following a Brachial Plexus Avulsion Injury: A Case Report.

Brachial plexus avulsion injuries result in permanent motor and sensory deficits, leading to debilitating symptoms. We report the case of a 25-year-old man with chronic pain following right-sided C5-T1 nerve root avulsion without evidence of peripheral nerve injury. His pain was recalcitrant to medical and neurosurgical interventions. However, he experienced substantial (>70%) pain relief with peripheral nerve stimulation targeting the median nerve. These results agree with data suggesting collateral sprouting of sensory nerves occurs following a brachial plexus injury. Further study is needed if we are to understand the mechanisms of the peripheral nerve stimulator as a treatment option.

Herpes Zoster Ophthalmicus Discovered During Pain Consult Possibly Complicated With Dural Sinus Thrombosis and Refractory Headache Managed With Ketamine: A Case Report.

Pain is a common symptom associated with shingles and may precede the onset of the characteristic rash. In the context of herpes zoster ophthalmicus, pain can manifest with severe headaches, posing challenges due to other potentially life-threatening conditions such as stroke and intracranial hypertension. In this report, we present the case of a 51-year-old male with severe headache and imaging findings of dural sinus thrombosis. He was later diagnosed with herpes zoster ophthalmicus and required aggressive inpatient management of neuropathic pain. Despite appropriate treatment, acute herpes zoster can progress to post-herpetic neuralgia, requiring long-term pain management.

Pharmacist-led improvement in perioperative antibiotic selection for patients with a penicillin allergy label.

PURPOSE: Surgical patients with a penicillin allergy label (PAL) are less likely to receive ß-lactams for surgical site infection (SSI) prophylaxis and more likely to receive second-line antibiotics, which may increase the risk of SSI, drug toxicities, and associated costs. We assessed the impact of implementing a pharmacist-led quality improvement project to increase the use of cefazolin as a first-line agent in this population. SUMMARY: After implementation of a pilot project in December 2021, all patients with a PAL and orders for preoperative antibiotics were risk stratified into high- or low-risk categories by a pharmacist. For the low-risk group, cefazolin was recommended. For the high-risk group, cefazolin was avoided and a second-line agent was administered. Our analysis compared 422 preintervention patients (August 15 to November 15, 2021) to 492 postintervention patients (December 15 to March 15, 2022). During the postintervention period, ß-lactam usage increased (from 12.6% to 37.8%, P < 0.001), while usage of vancomycin (45.5% vs 29.5%, P < 0.001) and other second-line antibiotics (87.4% vs 62.2%, P < 0.001) declined. There were no adverse reactions reported in the preintervention cohort, with 2 potential adverse reactions reported after the intervention (0% vs 0.4%, P = 0.190). Medication costs based on claims data were 50% to 80% lower for patients receiving cefazolin. CONCLUSION: In our cohort, a pharmacy-led antibiotic selection algorithm for patients with a PAL receiving perioperative antimicrobial prophylaxis resulted in increased use of ß-lactam antibiotics, decreased use of second-line antibiotics, and decreased costs without a significant change in the incidence of adverse reactions.

Genome-wide Analysis of Motor Progression in Parkinson Disease.

Background and Objectives: The genetic basis of Parkinson disease (PD) motor progression is largely unknown. Previous studies of the genetics of PD progression have included small cohorts and shown a limited overlap with genetic PD risk factors from case-control studies. Here, we have studied genomic variation associated with PD motor severity and early-stage progression in large longitudinal cohorts to help to define the biology of PD progression and potential new drug targets. Methods: We performed a GWAS meta-analysis of early PD motor severity and progression up to 3 years from study entry. We used linear mixed-effect models with additive effects, corrected for age at diagnosis, sex, and the first 5 genetic principal components to assess variability in axial, limb, and total Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III scores. Results: We included 3,572 unrelated European ancestry patients with PD from 5 observational cohorts and 1 drug trial. The average AAO was 62.6 years (SD = 9.83), and 63% of participants were male. We found an average increase in the total MDS-UPDRS III score of 2.3 points/year. We identified an association between PD axial motor progression and variation at the GJA5 locus at 1q12 (ß = -0.25, SE = 0.04, p = 3.4e-10). Exploration of the regulation of gene expression in the region (cis-expression quantitative trait loci [eQTL] analysis) showed that the lead variant was associated with expression of ACP6, a lysophosphatidic acid phosphatase that regulates mitochondrial lipid biosynthesis (cis-eQTL p-values in blood and brain RNA expression data sets: <10-14 in eQTLGen and 10-7 in PsychEncode). Discussion: Our study highlights the potential role of mitochondrial lipid homeostasis in the progression of PD, which may be important in establishing new drug targets that might modify disease progression.

Pain Associated With Monkeypox Virus: A Rapid Review.

International concerns for another pandemic arose after emerging reports of an ongoing outbreak of the monkeypox virus (MPXV) in Europe and the United States in 2022. Severe pain is one of the most distressing complications for patients in the current outbreak, but there is a general paucity of relevant peer-reviewed medical literature from which to draw clear recommendations on appropriate pain therapies. The Centers for Disease Control recently published a letter in July 2022 urging providers to conduct further studies concerning pain management. Thus, a rapid literature search was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of several databases from inception until August 19, 2022, was conducted. All published studies describing pain in patients who tested positive for MPXV with original data and written in English were included. Sixty-nine studies were initially identified for screening. After initial screening, 27 papers were considered for full-text review, and 15 papers met the inclusion criteria. A total of 1043 positive cases were included in this study. Most patients were men. Treatment options proposed by the authors include acetaminophen, ibuprofen, opioids, lidocaine gel, metamizole, and rectal suppositories containing emollients or steroids with oral laxatives for severe anal pain. Although most cases were mild requiring outpatient treatment, a considerable number of patients were admitted due to serious complications. Severe pain was often the reason to seek medical attention and hospital admission for pain control. Analgesic plans included oral and topical analgesia. In severe cases, pain was managed with opioids. To our knowledge, this rapid review is the first study to comprehensively summarize proposed treatments for pain associated with MPXV. Guidelines may be needed to help direct the best management to avoid morbidity in patients, particularly as adjuvants may play a key role but are not commonly utilized in published reports.