Retromer-dependent lysosomal stress in Parkinson's disease.

While causative mutations in complex disorders are rare, they can be used to extract a biological pathway whose pathogenicity can generalize to common forms of the disease. Here we begin by relying on the biological consequences of mutations in LRRK2 and VPS35, genetic causes of autosomal-dominant Parkinson's disease, to hypothesize that 'Retromer-dependent lysosomal stress' represents a pathway that can generalize to idiopathic Parkinson's disease. Next, we outline a series of studies that can test this hypothesis, including the development of biomarkers of pathway dysfunction. If validated, the hypothesis can suggest a unified mechanism of disease and might inform future diagnostic and therapeutic investigations. This article is part of a discussion meeting issue 'Understanding the endo-lysosomal network in neurodegeneration'.

Implementation strategies of cervical cancer screening in South Asia: A systematic review.

BACKGROUND: Cervical cancer is a preventable cancer by screening, vaccination and timely management of preinvasive cervical lesions. However, about 90% of the global burden of cervical cancer is reported from developing countries. OBJECTIVE: This systematic review aimed to analyze the strategies implemented for cervical cancer screening in South Asia. SEARCH STRATEGY: An electronic search of PubMed/MEDLINE, Scopus and Google Scholar was carried out for articles published in English, evaluating the implementation of cervical cancer screening between December 2000 and June 2023 in South Asia using appropriate search terms. SELECTION CRITERIA: Cross-sectional studies, randomized control trials (RCTs) or non-randomized controlled trials evaluating different cervical screening strategies were included. DATA COLLECTION AND ANALYSIS: A three-stage selection process was performed using a validated proforma including the title, author, year of publication, objective, country, study design, screening methods, strategies and outcomes, and results. The systematic review was designed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The risk of bias was evaluated with the National Heart, Lung, and Blood Institute's (NHLBI) Quality Assessment Tools. MAIN RESULTS: Out of the initial 1135 articles reviewed systematically, 23 studies met the inclusion criteria and were included in the qualitative synthesis of results. The implementation outcomes measured were acceptability (n = 23 100%), feasibility (n = 22, 95.7%), fidelity (n = 14, 60.9%), sustainability (n = 7, 30.4%), coverage (n = 4, 17.4%) and cost (n = 1, 4.3%). CONCLUSION: Cervical cancer screening can be effectively implemented by restructuring the ongoing programs.

Quality of life following a maternal near-miss event during the COVID-19 pandemic at a tertiary care center in South India.

OBJECTIVE: To assess the quality of life (QoL) in women following a maternal near-miss event and to assess the women's attitude towards future fertility and their contraceptive choices. METHODS: A cross-sectional observational study was conducted in Government Medical College, Kozhikode, India among women who had experienced a near-miss event (n = 50) between January 1, 2020 and May 31, 2021 during the peak of the COVID-19 pandemic. The QoL was assessed using the WHO Quality of Life, BREF Version, questionnaire, which was administered to the consenting participants over phone. Information regarding desire for future fertility, contraceptive choices, and urogenital symptoms was also collected. A comparison between the short-term and long-term effects on the QoL was also done. RESULTS: A maternal near-miss event was not found to adversely affect the overall quality of life in the present study. The scores in all the four domains-physical, psychological, social relationships, and environmental-suggested good QoL, although greater variability in values were observed in the physical and psychological domains. The influence in these two domains was more pronounced following a perinatal loss and following prolonged physical morbidities. There was no difference in short- and long-term QoL following a maternal near miss (MNM). The MNM did not influence the contraceptive choices and there was no subsequent pelvic floor dysfunction in most women. CONCLUSION: MNM was not found to adversely affect the overall subsequent QoL in the present study. There was no difference in short- and long-term QoL following a MNM. Studies carried out over a longer period of time with a control group would yield more information.

Impact of Air Conditioners on Sick Building Syndrome, Sickness Absenteeism, and Lung Functions.

Introduction: Modernization has led to greater usage of Air Conditioners (ACs) in our daily lives. It is observed that the occupants of office buildings with ACs consistently report on average more symptoms than do occupants of office buildings with natural ventilation referred to as Sick Building Syndrome (SBS). The appearance of symptoms reduces work efficiency and increases absenteeism due to sickness (sickness absenteeism). Therefore, the present study was planned to evaluate the impact of usage of ACs on SBS and to find out the association of ACs with sickness absenteeism and lung function tests. Materials and Methods: This study was conducted on 200 healthy non-smoker adults in the age group of 18 to 45 years who were using ACs for at least 6 to 8 h/day for more than 2 years (group I). And 200 healthy adults, age and gender-matched, with the same work pattern, not using ACs at all served as controls (group II). The basic information on the usage of ACs and the prevalence of discomfort related to neural symptoms, respiratory symptoms, and skin and mucous membrane related to SBS was obtained through a questionnaire. Results: The building-related symptoms in group I males were more compared to group II males and significantly higher in group I males compared to females. We observed that the appearance of symptoms of SBS led to sickness absenteeism among group I participants. Lung function tests especially FVC, FEV1, PEFR, and MVV were significantly reduced among group I males and females compared to group II males and females. Conclusion: ACs have a profound effect on the quality of the air we breathe and on human health than just lowering the temperature. There is a higher prevalence of SBS-Respiratory and allergic symptoms in AC users.

LRRK2 and GBA1 variant carriers have higher urinary bis(monacylglycerol) phosphate concentrations in PPMI cohorts.

We quantified concentrations of three isoforms of the endolysosomal lipid, bis(monoacylglycerol) phosphate (BMP) in the urine of deeply phenotyped cohorts in the Parkinson's Progression Markers Initiative: LRRK2 G2019S PD (N = 134) and non-manifesting carriers (NMC) (G2019S+ NMC; N = 182), LRRK2 R1441G PD (N = 15) and R1441G+ NMC (N = 15), GBA1 N409S PD (N = 76) and N409S+ NMC (N = 178), sporadic PD (sPD, N = 379) and healthy controls (HC) (N = 190). The effects of each mutation and disease status were analyzed using nonparametric methods. Longitudinal changes in BMP levels were analyzed using linear mixed models. At baseline, all LRRK2 carriers had 3-7× higher BMP levels compared to HC, irrespective of the disease status. GBA1 N409S carriers also showed significant, albeit smaller, elevation (~30-40%) in BMP levels compared to HC. In LRRK2 G2019S PD, urinary BMP levels remained stable over two years. Furthermore, baseline BMP levels did not predict disease progression as measured by striatal DaT imaging, MDS-UPDRS III Off, or MoCA in any of the cohorts. These data support the utility of BMP as a target modulation biomarker in therapeutic trials of genetic and sPD but not as a prognostic or disease progression biomarker.

Nano Hydroxyapatite for Biomedical Applications Derived from Chemical and Natural Sources by Simple Precipitation Method.

In the past, bone fractures due to accidents were rectified by surgery and reconstruction of bone structure. In recent times, researchers have been made to find a solution by producing alternate biomaterials. Hydroxyapatite (HAp) is one of the most important bioactive materials used as a substitute for human hard tissue because of its composition being very similar to human bones and teeth. A study has proved that HAp has been used for bone regeneration in clinical trials in the mid-1980. HAp has been used as implant coatings and graft materials and also used as granules, cement, and pastes for bone regenerative applications. HAp coatings on bioimplants improved biocompatibility, bioactivity, and biological fixation. Moreover, some of the deposition methods can be employed to increase the cellular responses of bone regeneration such as sputtering, spraying, electrodeposition, and pulsed layer deposition. The researcher has prepared hydroxyapatite from chemical and natural sources. The surface area and intrinsic properties of the HAp play a vital role in bone-related applications. This can be achieved by synthesizing the HAp from natural sources rather than synthetic materials. The HAp obtained from the chemical source is not fulfilling the requirements of the natural bone. A variety of biowaste materials such as eggshell, crab shell, snail shell, bovine bone, fishbone, and fish scales are available in nature and can be converted to useful calcium source for HAp. The present study is to produce the HAp from biowaste materials like eggshell and chemical sources using the wet precipitation method. The synthesized HAp is coated on the Ti6Al4V alloy using the electrodeposition method, and it is immersed in SBF solution at 37 °C for corrosion testing. The coated samples are investigated by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), electrochemical study, field emission scanning electron icroscopy (FESEM), energy dispersive X-ray analysis (EDAX), AFM, and antibacterial activity with two different microorganisms. FTIR and XRD confirm the functional groups and crystallinity of the HAp. The good antibacterial activity of the HAp is observed against two bacterial strains. The corrosion studies reveal that the HAp derived from a natural source is eco-friendly and nontoxic and has excellent corrosion resistivity and cell adhesion properties. A strong bond is formed between the naturally derived HAp with bone tissue which is involved in the bio-resorption process and does not pose any side effect to the human body compared to synthetically derived HAp. In addition, the biowaste materials are converted to useful biomaterials and can reduce environmental pollution.

Detectability of Small Low-Attenuation Lesions With Deep Learning CT Image Reconstruction: A 24-Reader Phantom Study.

BACKGROUND. Iterative reconstruction (IR) techniques are susceptible to contrast-dependent spatial resolution, limiting overall radiation dose reduction potential. Deep learning image reconstruction (DLIR) may mitigate this limitation. OBJECTIVE. The purpose of our study was to evaluate low-contrast detectability performance and radiation-saving potential of a DLIR algorithm in comparison with filtered back projection (FBP) and IR using a human multireader noninferiority study design and task-based observer modeling. METHODS. A dual-phantom construct, consisting of a low-contrast detectability module (21 low-contrast hypoattenuating objects in seven sizes [2.4-10.0 mm] and three contrast levels [-15, -10, -5 HU] embedded within liver-equivalent background) and a phantom, was imaged at five radiation exposures (CTDIvol range, 1.4-14.0 mGy; size-specific dose estimate, 2.5-25.0 mGy; 90%-, 70%-, 50%-, and 30%-reduced radiation levels and full radiation level) using an MDCT scanner. Images were reconstructed using FBP, hybrid IR (ASiR-V), and DLIR (TrueFidelity). Twenty-four readers of varying experience levels evaluated images using a two-alternative forced choice. A task-based observer model (detectability index [d']) was calculated. Reader performance was estimated by calculating the AUC using a noninferiority method. RESULTS. Compared with FBP and IR methods at routine radiation levels, DLIR medium and DLIR high settings showed noninferior performance through a 90% radiation reduction (except DLIR medium setting at 70% reduced level). The IR method was non-inferior to routine radiation FBP only for 30% and 50% radiation reductions. No significant difference in d' was observed between routine radiation FBP and DLIR high setting through a 70% radiation reduction. Reader experience was not correlated with diagnostic accuracy (R2 = 0.005). CONCLUSION. Compared with FBP or IR methods at routine radiation levels, certain DLIR algorithm weightings yielded noninferior low-contrast detectability with radiation reductions of up to 90% as measured by 24 human readers and up to 70% as assessed by a task-based observer model. CLINICAL IMPACT. DLIR has substantial potential to preserve contrast-dependent spatial resolution for the detection of hypoattenuating lesions at decreased radiation levels in a phantom model, addressing a major shortcoming of current IR techniques.

Can Artificial Intelligence Replace the Unique Nursing Role?

Artificial intelligence (AI) is transforming healthcare, offering potential benefits and challenges. In healthcare, AI enhances efficiency, streamlines processes, and supports decision-making. However, challenges include potential errors and biases in algorithms, data privacy concerns, legal and ethical issues, and resistance to change. In nursing, a delicate balance emerges between AI and human touch. While AI aids in data-driven decision-making and administrative tasks, it lacks the emotional intelligence, empathy, and nuanced understanding crucial to nursing care. Nurses excel in critical thinking, adaptability to dynamic situations, patient advocacy, collaboration, and establishing human connections. AI supports these functions by automating routine tasks and offering decision support tools, yet its rigidity in dynamic situations and lack of human touch pose limitations. This review underscores the necessity of careful AI integration in healthcare, acknowledging its advantages while mitigating drawbacks. In nursing, the symbiosis between AI and human qualities is vital. The role of AI should be to complement, not replace, the unique skills and empathetic aspects of nursing care. Addressing concerns related to bias, transparency, data privacy, and professional training is essential for maximizing the benefits of AI in healthcare while preserving the human touch in patient care. This article explores whether AI can replace unique nursing roles.

U.S. Diagnostic Reference Levels and Achievable Doses for 10 Pediatric CT Examinations.

Background Diagnostic reference levels (DRLs) and achievable doses (ADs) were developed for the 10 most commonly performed pediatric CT examinations in the United States using the American College of Radiology Dose Index Registry. Purpose To develop robust, current, national DRLs and ADs for the 10 most commonly performed pediatric CT examinations as a function of patient age and size. Materials and Methods Data on 10 pediatric (ie, patients aged 18 years and younger) CT examinations performed between 2016 and 2020 at 1625 facilities were analyzed. For head and neck examinations, dose indexes were analyzed based on patient age; for body examinations, dose indexes were analyzed for patient age and effective diameter. Data from 1 543 535 examinations provided medians for AD and 75th percentiles for DRLs for volume CT dose index (CTDIvol), dose-length product (DLP), and size-specific dose estimate (SSDE). Results Of all facilities analyzed, 66% of the facilities (1068 of 1625) were community hospitals, 16% (264 of 1625) were freestanding centers, 9.5% (154 of 1625) were academic facilities, and 3.5% (57 of 1625) were dedicated children's hospitals. Fifty-two percent of the patients (798 577 of 1 543 535) were boys, and 48% (744 958 of 1 543 535) were girls. The median age of patients was 14 years (boys, 13 years; girls, 15 years). The head was the most frequent anatomy examined with CT (876 655 of 1 543 535 examinations [57%]). For head without contrast material CT examinations, the age-based CTDIvol AD ranged from 19 to 46 mGy, and DRL ranged from 23 to 55 mGy, with both AD and DRL increasing with age. For body examinations, DRLs and ADs for size-based CTDIvol, SSDE, and DLP increased consistently with the patient's effective diameter. Conclusion Diagnostic reference levels and achievable doses as a function of patient age and effective diameter were developed for the 10 most commonly performed CT pediatric examinations using American College of Radiology Dose Index Registry data. These benchmarks can guide CT facilities in adjusting pediatric CT protocols and resultant doses for their patients. © RSNA, 2021 An earlier incorrect version appeared online. This article was corrected on October 29, 2021.

Plasma Glucosylsphingosine in GBA1 Mutation Carriers with and without Parkinson's Disease.

BACKGROUND: Biallelic mutations in the GBA1 gene encoding glucocerebrosidase cause Gaucher's disease, whereas heterozygous carriers are at risk for Parkinson's disease (PD). Glucosylsphingosine is a clinically meaningful biomarker of Gaucher's disease but could not be assayed previously in heterozygous GBA1 carriers. OBJECTIVE: The aim of this study was to assess plasma glucosylsphingosine levels in GBA1 N370S carriers with and without PD. METHODS: Glucosylsphingosine, glucosylceramide, and four other lipids were quantified in plasma from N370S heterozygotes with (n = 20) or without (n = 20) PD, healthy controls (n = 20), idiopathic PD (n = 20), and four N370S homozygotes (positive controls; Gaucher's/PD) using quantitative ultra-performance liquid chromatography tandem mass spectrometry. RESULTS: Plasma glucosylsphingosine was significantly higher in N370S heterozygotes compared with noncarriers, independent of disease status. As expected, Gaucher's/PD cases showed increases in both glucocerebrosidase substrates, glucosylsphingosine and glucosylceramide. CONCLUSIONS: Plasma glucosylsphingosine accumulation in N370S heterozygotes shown in this study opens up its future assessment as a clinically meaningful biomarker of GBA1-PD. © 2021 International Parkinson and Movement Disorder Society.

Strategies to Optimize Nephrolithiasis Emergency Care (STONE): Prospective Evaluation of an Emergency Department Clinical Pathway.

OBJECTIVE: To convene a multi-disciplinary panel to develop a pathway for Emergency Department (ED) patients with suspected nephrolithiasis and then prospectively evaluate its effect on patient care. MATERIALS AND METHODS: The STONE Pathway was developed and linked to order sets within our Electronic Health Record in April 2019. Records were prospectively reviewed for ED patients who underwent ultrasound or Computerized Tomography (CT) to evaluate suspected nephrolithiasis between January 2019 and August 2019 within our institution. The primary outcome measure was the proportion of patients whose ED CT was low dose (<4 mSv). Secondary outcome measures included receipt of pathway-concordant pain medications and urine strainers. Order set utilization was evaluated as a process measure. Balance measures assessed included repeat ED visits, imaging, hospitalizations, and a urologic clinic visit or surgery within 30 days of discharge. RESULTS: 441 patients underwent ED imaging, of whom 261 (59%) were evaluated for suspected nephrolithiasis. The STONE Pathway was used in 50 (30%) eligible patients. Patients treated with the Pathway were more likely to undergo low-dose CTs (49% vs 23%, P <.001), and receive guideline-concordant pain medications such as NSAIDs (90% vs 62%, P <.001), and were less likely to return to the ED within 30 days (13% vs 2%, P = .01). These measures demonstrated special cause variation following Pathway release. CONCLUSION: Clinical pathways increase compliance with evidence-based practices for pain control and imaging in nephrolithiasis emergency care and may improve the delivery of value-based care.

Pathophysiology and Clinical Presentation of COVID-19 in Children: Systematic Review of the Literature.

Introduction: Coronavirus disease 2019 (COVID-19) is due to severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection, which belongs to beta-coronaviruses of the Coronaviridae family. SARS-coV-2 causes acute respiratory infection with varying severity in different age groups, wherein adults can develop severe disease, while children are relatively spared until now, with COVID-19 in children accounting for only 1-5% of diagnosed cases. Although COVID-19 incidence rate in children is relatively low, their protection from COVID-19 is still a matter of increasing concern as children constitute a large vulnerable population. In order to develop effective therapeutic management and preventive measures against COVID-19 in children, there is an urgent need for a better understanding of its pathophysiology at the molecular level and clinical presentation as well as possible protective mechanisms in the pediatric population. Objectives: There is limited data regarding the incidence and clinical presentation of SARS-CoV-2 infection in children. Our goal was to understand the clinical picture and presentation of pediatric patients with confirmed COVID-19. Methods: A systematic literature search of popular medical databases (PubMed, Cochrane Central Register of Clinical Trials and Scopus), restricted to English language publications only, was conducted by us. We chose published peer-reviewed and cross-sectional articles as well as case series providing clinical signs, imaging findings and laboratory results of pediatric patients, using the following inclusion criteria: children aged up to 18 years who tested positive for COVID-19 and in whom SARS-Co-V-2 was detected in the nasal/throat swab by real time polymerase chain reaction (RT-PCR). Conclusion: Our review revealed that, in children, COVID-19 was milder in terms of disease severity and clinical presentation, and it had a better prognosis and a lower mortality rate than adults.

Findings of the AAPM Ad Hoc committee on magnetic resonance imaging in radiation therapy: Unmet needs, opportunities, and recommendations.

The past decade has seen the increasing integration of magnetic resonance (MR) imaging into radiation therapy (RT). This growth can be contributed to multiple factors, including hardware and software advances that have allowed the acquisition of high-resolution volumetric data of RT patients in their treatment position (also known as MR simulation) and the development of methods to image and quantify tissue function and response to therapy. More recently, the advent of MR-guided radiation therapy (MRgRT) - achieved through the integration of MR imaging systems and linear accelerators - has further accelerated this trend. As MR imaging in RT techniques and technologies, such as MRgRT, gain regulatory approval worldwide, these systems will begin to propagate beyond tertiary care academic medical centers and into more community-based health systems and hospitals, creating new opportunities to provide advanced treatment options to a broader patient population. Accompanying these opportunities are unique challenges related to their adaptation, adoption, and use including modification of hardware and software to meet the unique and distinct demands of MR imaging in RT, the need for standardization of imaging techniques and protocols, education of the broader RT community (particularly in regards to MR safety) as well as the need to continue and support research, and development in this space. In response to this, an ad hoc committee of the American Association of Physicists in Medicine (AAPM) was formed to identify the unmet needs, roadblocks, and opportunities within this space. The purpose of this document is to report on the major findings and recommendations identified. Importantly, the provided recommendations represent the consensus opinions of the committee's membership, which were submitted in the committee's report to the AAPM Board of Directors. In addition, AAPM ad hoc committee reports differ from AAPM task group reports in that ad hoc committee reports are neither reviewed nor ultimately approved by the committee's parent groups, including at the council and executive committee level. Thus, the recommendations given in this summary should not be construed as being endorsed by or official recommendations from the AAPM.

Through-the-Glass Portable Radiography of Patients in Isolation Units: Experience During the COVID-19 Pandemic.

OBJECTIVE. To reduce staff exposure to infection and maintain operational efficiency, we have developed a protocol to image patients using portable chest radiography through the glass of an isolation room. This technique is safe and easy to implement. Images are of comparable quality to standard portable radiographs. CONCLUSION. This protocol, used routinely by our department during the COVID-19 pandemic, can be applied to any situation in which the patient is placed in isolation.