Pharmacokinetics of tenofovir alafenamide, emtricitabine, and dolutegravir in a patient on peritoneal dialysis.

INTRODUCTION: Peritoneal dialysis (PD) is an effective renal replacement modality in people with HIV (PWH) with end-stage kidney disease (ESKD), particularly those with residual kidney function. Data on pharmacokinetics (PK) of antiretrovirals in patients on peritoneal dialysis are limited. METHODS: A single-participant study was performed on a 49-year-old gentleman with ESKD on PD and controlled HIV on once daily dolutegravir (DTG) 50 mg + tenofovir alafenamide (TAF) 25 mg / emtricitabine (FTC) 200 mg. He underwent serial blood plasma, peripheral blood mononuclear cell, and urine PK measurements over 24 h after an observed DTG + FTC/TAF dose. RESULTS: Plasma trough (Cmin) concentrations of TAF, tenofovir (TFV), FTC, and DTG were 0.05, 164, 1,006, and 718 ng/mL, respectively. Intracellular trough concentrations of TFV-DP and FTC-TP were 1142 and 11,201 fmol/million cells, respectively. Compared to published mean trough concentrations in PWH with normal kidney function, observed TFV and FTC trough concentrations were 15.5- and 20-fold higher, while intracellular trough concentrations of TFV-DP and FTC-TP were 2.2-fold and 5.4-fold higher, respectively. TFV and FTC urine levels were 20 times lower than in people with normal GFR. CONCLUSIONS: In a single ESKD PWH on PD, daily TAF was associated with plasma TFV and intracellular TFV-DP trough concentrations 15-fold and 2-fold higher than those of people with uncompromised kidney function, potentially contributing to nephrotoxicity. This suggests that TFV accumulates on PD; thus, daily TAF in PD patients may require dose adjustment or regimen change to optimize treatment, minimize toxicity, and preserve residual kidney function.

The mediating role of cardiac patients' perception of nursing care on the relationship between kinesiophobia, anxiety and depression in rural hospitals: a cross-sectional study.

BACKGROUND: Kinesiophobia could act as a significant barrier against physical activity following cardiac procedures worsening cardiovascular health problems and potentially leading to conditions like hospital-acquired anxiety and depression among patients with cardiovascular disease (CVD). Nurses are the vanguard health care team who can aid patients in taking proactive steps to overcome fear of movement following cardiac procedures. AIM: The overarching aim is to investigate the relationship between kinesiophobia, anxiety and depression, and patients' perception of nursing care. METHOD: A descriptive correlational research design in two rural hospitals, conducted at cardiac intensive care units of Kafr Eldawar Hospital and Damanhur Medical National Institute. Data were collected from 265 nurses, using the following patient-reported outcome measures, the Tampa Scale for Kinesiophobia (TSK), the Hospital Anxiety and Depression Scale (HADS), the Person-Centered Critical Care Nursing Questionnaire (PCCNP) and the patients' demographic and clinical profile. RESULT: A significant negative correlation was found between HADS and PCCNP (r: -0.510, p < 0.001) however, Kinesiophobia was significantly and positively correlated (r: 0.271, p < 0.001). A direct effect of PCCNP in the presence of the mediator was found to be not statistically significant (-0.015, CR = 0.302, p = 0.763). Nonetheless, PCCNP indirectly affects kinesiophobia through HADS (p=-0.099). IMPLICATION FOR NURSING PRACTICE: Customizing individualized cardiac rehabilitation (CR) programs based on the emotional experience of cardiac patients will be conducive to rehabilitation and prognosis for patients, thereby lessening the physical burden and improving their quality of life.

CASE REPORT: Fulminant acute hemorrhagic Leukoencephalitis (AHLE): A rare and ruinous outcome with cerebral herniation (COVID-19).

Background: Acute hemorrhagic leukoencephalitis (AHLE) is a very rare demyelinating disease with rapid fulminant inflammation of the white matter. Although the exact etiology is unknown, AHLE usually manifests post a viral or bacterial infection and less often seen post vaccination for measles or rabies. AHLE has a very poor prognosis and a high mortality rate. Owing to the rarity of this entity there is not clear consensus on the proper line of management. In this report, we present a case of AHLE as a para-infectious sequel to COVID-19 in a young patient. Clinical presentation: We report a 30-year-old turkish patient with an initial presentation of upper respiratory tract infection due to COVID-19. Initially, she was admitted to the hospital with generalized tonic-clonic seizure (GTCS) and deterioration in her level of consciousness lapsing into a coma. An initial CT scan showed diffuse brain edema and an MRI head confirmed the suspicion of Acute hemorrhagic leukoencephalitis (AHLE). Despite prompt and diligent osmotic therapy and pulsed intravenous (IV) methylprednisolone, her condition rapidly depreciated and progressed into cerebral edema with gravid sequela of brainstem herniation. Conclusions: AHLE is a very rare entity and perhaps its fulminant debilitating course and high mortality should warrant further studies on disease pathophysiology and its optimal treatment parameters. Life-saving decompressive hemicraniectomy should be considered in the multidisciplinary approach of the management with tailored osmotic and immunotherapy.

Atypical Duplex appendix arising from the ascending colon: a case report.

BACKGROUND: Duplex or vermiform appendix refers to the presence of an appendix beside the naturally occurring one. Although, duplex appendix emerges from the caecum most of the time, yet it is encountered in other parts of the colon. Inflammation of duplex appendix may represent not only a clinical, but also a surgical dilemma, and this would be confusing further among patients who already had prior appendectomy. CASE PRESENTATION: We present a case of 29-years old Egyptian male patient with history of appendectomy one and half year before presenting to the emergency department with recurrent acute abdominal pain that was linked to duplex appendicitis abnormally emerged from the mid-ascending colon. The first episode was treated conservatively considering atypical right colon diverticulitis as a potential differential diagnosis. Seven months later the patient was treated by laparoscopic appendectomy and experienced an uneventful pot-operative course. CONCLUSION: Duplex appendicitis, though rare, should be considered in the differential diagnosis of recurrent acute abdomen even after appendectomy.

Perceived stress, coping strategies, symptoms severity and function status among carpal tunnel syndrome patients: a nurse-led correlational Study.

BACKGROUND: Carpal tunnel syndrome (CTS) is a prevalent condition characterized by hand pain, tingling, and numbness. The severity of symptoms and functional status in CTS patients may be influenced by perceived stress and how individuals cope with it. However, scarce knowledge exists about the role of coping strategies as moderators in this relationship. Unfolding the role of perceived stress and coping strategies for CTS management will help the nurse to provide comprehensive and tailored nursing care. This will ultimately improve patient comfort, functionality, and quality of life. PURPOSES: This study aimed to examine the role of coping strategies (adaptive and maladaptive) in the relationship between perceived stress and both symptoms severity and function status among those patients. METHOD: We employed a multisite, correlational study design with moderation analysis. The study included 215 patients with CTS from neurosurgery outpatient clinics at three hospitals in Egypt. After obtaining their consent to participate, eligible participants completed anonymous, self-reported measures of perceived stress, the brief COPE inventory, and the Boston Carpal Tunnel Questionnaire. Demographic and biomedical data were also collected. The questionnaire took about 20 min to be completed. The data was collected over six months, starting in February 2023. RESULTS: The results showed that perceived stress, adaptive coping, and maladaptive coping were significant predictors of symptoms severity and functional status. Adaptive coping moderated the relationships between perceived stress and both symptoms severity and function status, while maladaptive coping did not. The interaction between perceived stress and adaptive coping explained a moderate effect on symptoms severity and function status after controlling for the main effects and the covariates. CONCLUSION: This study explored the relationship between perceived stress, coping strategies, and outcomes in patients with CTS. The results indicate that nurses play a vital role in assessing and assisting patients to adopt effective coping strategies to manage perceived stress and alleviate symptoms and functional impairment. Moreover, the findings support the need for psychological interventions that address both perceived stress and coping strategies as a way to enhance the functioning status and quality of life of patients with CTS.

Climate anxiety, environmental attitude, and job engagement among nursing university colleagues: a multicenter descriptive study.

BACKGROUND: Climate change, a pervasive global phenomenon, exerts discernible impacts on the physical, social, and psychological dimensions of well-being. The apprehension surrounding this complex environmental issue has reached a critical juncture, with over 76,000 individuals across more than thirty nations expressing profound levels of concern, characterizing their anxiety as either "very" or "extremely" pronounced. This surge in awareness regarding the potential consequences of climate change has given rise to an emergent and escalating challenge known as climate anxiety. This distinctive form of anxiety manifests through profound feelings of fear, helplessness, and despair elicited by the impending repercussions of climate change. Notably, the intersection of climate anxiety with occupational domains, particularly within the context of Nursing University Colleagues, suggests a nuanced relationship with job engagement, wherein the psychological responses to climate change may influence professional commitment and involvement. AIM OF THE STUDY: To examine the correlation among Climate Anxiety, Environmental Attitude, and Job Engagement among Nursing University Colleagues comprising eight distinct nursing faculties. DESIGN: A multicenter descriptive, cross-sectional research design study followed. SUBJECT: Three hundred fifty-nine participants from the Centre, Delta, West, Suez Canal, and Upper regions of Egypt using a stratified random cluster sampling technique. MEASUREMENTS: Social and health related to climate data structured questionnaire, climate anxiety scale, environmental attitude inventory, and job engagement scale. RESULTS: The influence of demographics on climate anxiety, environmental attitude, and job involvement was not observed. Nevertheless, geographical variations emerged as a noteworthy factor. A statistically significant inverse correlation was identified between climate anxiety, job engagement dimensions, and the overall score of environmental attitudes. CONCLUSION: Climate anxiety was strongly associated with environmental attitudes and job engagement among nursing university colleagues. Higher climate anxiety is associated with a lower attitude towards the environment and decreased job engagement. Additionally, a higher attitude towards the environment is associated with decreased overall engagement in participants' jobs. IMPLICATIONS: The study's patterns make it clear how important it is to provide targeted psycho-educational interventions to help reduce climate anxiety among the group of nursing university colleagues. The imperative lies not only in alleviating the immediate psychological distress associated with heightened climate anxiety but also in fostering adaptive coping mechanisms. By doing so, these interventions serve as instrumental tools in nurturing resilience, thereby fortifying the mental well-being of nursing professionals amidst the evolving landscape of climate-related concerns.

Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis.

Lupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney disease and mortality. Better therapeutic strategies are needed as only 30%-40% of patients completely respond to treatment. Noninvasive biomarkers of intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts of kidney inflammation, we studied the urine proteomic profiles of 225 patients with LN (573 samples) in the longitudinal Accelerating Medicines Partnership in RA/SLE cohort. Urinary biomarkers of monocyte/neutrophil degranulation (i.e., PR3, S100A8, azurocidin, catalase, cathepsins, MMP8), macrophage activation (i.e., CD163, CD206, galectin-1), wound healing/matrix degradation (i.e., nidogen-1, decorin), and IL-16 characterized the aggressive proliferative LN classes and significantly correlated with histological activity. A decline of these biomarkers after 3 months of treatment predicted the 1-year response more robustly than proteinuria, the standard of care (AUC: CD206 0.91, EGFR 0.9, CD163 0.89, proteinuria 0.8). Candidate biomarkers were validated and provide potentially treatable targets. We propose these biomarkers of intrarenal immunological activity as noninvasive tools to diagnose LN and guide treatment and as surrogate endpoints for clinical trials. These findings provide insights into the processes involved in LN activity. This data set is a public resource to generate and test hypotheses and validate biomarkers.

Hooked on technology: examining the co-occurrence of nomophobia and impulsive sensation seeking among nursing students.

BACKGROUND: Nomophobia, the crippling fear of being disconnected from mobile devices, is a burgeoning global concern. Given the critical nature of the profession of nursing students, understanding nomophobia's prevalence and potential impacts on patient care and professional conductors becomes even more crucial. AIM: This study explores the relationship between nomophobia and impulsive sensation-seeking among nursing students in Egypt. DESIGN AND METHODS: A multicenter cross-sectional survey was conducted with 1626 nursing students randomly selected from three universities across Egypt. TOOLS: The Arabic versions of the Nomophobia and Impulsive Sensation Seeking Questionnaires were employed to gather data. RESULTS: Our findings revealed that 40.3% of the surveyed nursing students exhibited severe nomophobia, indicating a substantial dependence on their mobile devices. Notably, this high prevalence was accompanied by a strong tendency towards impulsive sensation-seeking behaviors. Furthermore, a stepwise regression analysis identified several significant predictors of nomophobia (p < 0.001). Impulsive sensation-seeking, year of study, average daily smartphone usage, and age emerged as key factors, explaining 27.5% of the variability in nomophobia scores. CONCLUSION: The prevalence of nomophobia among Egyptian nursing students is undeniable, highlighting their substantial reliance on mobile devices. A significant association with impulsive sensation-seeking behavior further compounds this dependence. Factors such as impulsive sensation seeking, year of study, average daily smartphone usage, and age were identified as significant predictors of nomophobia. Recognizing these factors as key predictors of nomophobia is crucial for designing effective interventions and psychotherapies. Prioritizing such interventions can promote future nurses' well-being and ensure they deliver the highest quality care to their patients.

Tuberculous Meningitis Presenting with Bilateral Optic Neuritis: A Case Report and Review of Literature.

Introduction: Tuberculosis (TB) is a major global cause of morbidity and mortality. TB meningitis (TBM) is an implication of systemic dissemination of a primary TB infection that indicates a poorer disease prognosis with various long-term neurological sequelae. Consequently, it is crucial to understand the different clinical presentations and manifestations of such condition. In TBM, vision loss, which is one of the most devastating complications, may result from optic nerve inflammation and atrophy. Although unilateral optic neuritis as a primary presenting symptom of TBM has been broadly reported in the literature, there is a paucity of information related to several other rare neuro-ophthalmic features, such as bilateral optic nerve involvement in TBM. Case Presentation: We herein present a case of a 37-year-old Indian male patient presenting with unilateral vision loss that subsequently progressed to bilateral vision loss and was hence diagnosed with bilateral optic neuritis. Additional thorough investigation yielded a diagnosis of TBM with underlying tuberculomas. The patient's condition improved afterward with anti-tuberculous therapy and steroids with follow-up magnetic resonance imaging indicating radiological resolution as well. Conclusion: The differential diagnosis of bilateral optic neuritis is broad but rare, yet an overlooked one would be central nervous system TB in the form of meningitis or tuberculoma. Hence, it is important to identify bilateral optic neuritis as a possible rare presenting symptom of an underlying central nervous system TB infection which could lead to a faster disease diagnosis and treatment to prevent its devastating complications.

Outcomes and management of kidney transplant recipients with Fabry disease: a review.

Fabry disease is an X-linked inheritable lysosomal storage disease caused by various mutations of the galactosidase α gene resulting in α-galactosidase deficiency. Chronic kidney disease (CKD) is one of the most significant consequences of Fabry disease, with risk of end-stage kidney disease (ESKD) in this population. Like for other patients with ESKD, kidney transplant is the optimal treatment for Fabry disease patients with ESKD. However, enzyme replacement therapy and newer Fabry disease treatments remain important to mitigate other end organ damage such as cardiomyopathy post transplantation. This review is a primer on Fabry disease, which examines the outcomes of disease in the context of kidney transplant prior to, and during, the enzyme replacement treatment era, medical treatment of kidney transplant recipients with Fabry disease, and progress in screening studies.

Compassion fatigue and stress related to cardiopulmonary resuscitation: a study of critical care nurses' experiences.

BACKGROUND: Cardiopulmonary resuscitation (CPR) is considered one of the most stressful experiences in critical care nursing; it directly and indirectly leads to compassion fatigue and burnout. AIM: Determine the levels of and relationship between postcode stress and compassion fatigue. DESIGN AND METHODS: A descriptive-correlational study using 300 critical care nurses from five intensive care units in two hospitals was conducted. TOOLS: Demographic and work-related data, the Postcode Stress Scale, and the Professional Quality of Life Scale: Compassion Fatigue subscale. RESULTS: Nurses had moderate to high postcode stress and compassion fatigue (67.98 ± 16.39 and 65.40±14.34, respectively). Moreover, there was a significant positive correlation between postcode stress, burnout (r=0.350, p=<0.001), secondary traumatic stress (r=0.518, p=<0.001), and subsequently, compassion fatigue (r=0.449, p=<0.001). In addition, higher levels of postcode stress were associated with higher levels of compassion fatigue with its subscales: burnout and secondary traumatic stress, with a coefficient of determination for compassion fatigue (0.199), burnout subscale (0.121), and secondary traumatic stress (0.266). CONCLUSION: Critical care nurses involved in resuscitation experiences are susceptible to postcode stress, burnout, secondary traumatic stress, and compassion fatigue. There is a significant relationship between these factors, with higher levels of postcode stress contributing to higher levels of compassion fatigue and its subscales: burnout and secondary traumatic stress. These results highlight the importance of addressing and managing the psychological well-being of nurses in resuscitation settings to mitigate the adverse effects of stress and promote their overall resilience and well-being.

Single Nucleus RNA Sequencing of Remnant Kidney Biopsies and Urine Cell RNA Sequencing Reveal Cell Specific Markers of Covid-19 Acute Kidney Injury.

Acute kidney injury (AKI) in COVID-19 patients is associated with high mortality and morbidity. Critically ill COVID-19 patients are at twice the risk of in-hospital mortality compared to non-COVID AKI patients. We know little about the cell-specific mechanism in the kidney that contributes to worse clinical outcomes in these patients. New generation single cell technologies have the potential to provide insights into physiological states and molecular mechanisms in COVID-AKI. One of the key limitations is that these patients are severely ill posing significant risks in procuring additional biopsy tissue. We recently generated single nucleus RNA-sequencing data using COVID-AKI patient biopsy tissue as part of the human kidney atlas. Here we describe this approach in detail and report deeper comparative analysis of snRNAseq of 4 COVID-AKI, 4 reference, and 6 non-COVID-AKI biopsies. We also generated and analyzed urine transcriptomics data to find overlapping COVID-AKI-enriched genes and their corresponding cell types in the kidney from snRNA-seq data. We identified all major and minor cell types and states by using by using less than a few cubic millimeters of leftover tissue after pathological workup in our approach. Differential expression analysis of COVID-AKI biopsies showed pathways enriched in viral response, WNT signaling, kidney development, and cytokines in several nephron epithelial cells. COVID-AKI profiles showed a much higher proportion of altered TAL cells than non-COVID AKI and the reference samples. In addition to kidney injury and fibrosis markers indicating robust remodeling we found that, 17 genes overlap between urine cell COVID-AKI transcriptome and the snRNA-seq data from COVID-AKI biopsies. A key feature was that several of the distal nephron and collecting system cell types express these markers. Some of these markers have been previously observed in COVID-19 studies suggesting a common mechanism of injury and potentially the kidney as one of the sources of soluble factors with a potential role in disease progression. Translational Statement: The manuscript describes innovation, application and discovery that impact clinical care in kidney disease. First, the approach to maximize use of remnant frozen clinical biopsies to inform on clinically relevant molecular features can augment existing pathological workflow for any frozen tissue without much change in the protocol. Second, this approach is transformational in medical crises such as pandemics where mechanistic insights are needed to evaluate organ injury, targets for drug therapy and diagnostic and prognostic markers. Third, the cell type specific and soluble markers identified and validated can be used for diagnoses or prognoses in AKI due to different etiologies and in multiorgan injury.

The association between body mass index elevation and differentiation in vitamin D receptor gene expression, genetic polymorphism, and oxidative stress in adult Egyptian individuals.

Vitamin D plays a central role in maintaining calcium, phosphorus, and bone homeostasis in close interaction with the parathyroid hormone. Obesity is a significant health problem worldwide, particularly in developed nations. The current study was carried out to investigate the possible relationship between body mass index (BMI) elevation and differentiation in 25-hydroxyvitamin D (VD), vitamin D receptor (VDR) gene expression, and genetic polymorphism besides oxidative stress in adult Egyptian individuals. This was done to explore the mechanisms underlying the suggested role of the VD/VDR complex in the pathogenesis of obesity. A total of 70 subjects (30 obese, 25 overweight, and 15 normal, age: 20-50 years, without other chronic diseases) were selected. The study focused on the determination of VD, VDR gene polymorphism, VDR gene expression, alkaline phosphatase, calcium, phosphorus, glucose, lipid profile, oxidative stress including, oxidant (malondialdehyde), and anti-oxidants (reduced glutathione and superoxide dismutase). The results showed that elevation in BMI led to the percentage of the Ff 'allele' becoming predominant, while the percentage of the FF 'allele' was in the normal BMI range. Also, BMI elevation caused significant reductions in VD and VDR expression, with significant elevations in alkaline phosphatase and the levels of calcium and phosphate in serum. Also, oxidative stress increases with increasing BMI. Elevation in BMI causes a reduction in VD concentration and VDR gene expression levels. Also, the percentage of heterozygous mutant genotype Ff 'allele' is predominantly in the obese human, in contrast to normal subjects, where the percentage of homozygous wild genotype FF 'allele' is predominant. In general, the genetic expression and polymorphism of VD and VDR can be used as a genetic marker for predisposition, diagnosis, prognosis, and progression of obesity.

The Effect of Distress Tolerance Training on Problematic Internet Use and Psychological Wellbeing Among Faculty Nursing Students: A Randomized Control Trial.

Background: Distress tolerance skills have the potential to decrease problematic internet use and improve psychological wellbeing by cognitive reframing and goal-oriented problem-solving. Aim: To assess the impact of distress tolerance training on problematic internet use and psychological wellbeing among university nursing students. Methods: A randomized control trial used at the faculty of nursing using simple random sampling method. Tools: Distress Tolerance Scale, problematic internet use questionnaire, and Ryff psychological wellbeing scale. Data were collected from 60 nursing students over a period of 4 months. Results: Distress tolerance level was increased among study group from 20.75±14.29 to 72.75±24.09 and sustained for 3 months to 62.44 ±20.77 with statistically significant (f=7.090, p=0.006) and large effect size 0.75. When compared to no change among the control group as mean scare start by 22.35±14.29 to 23.44±16.09 and after 3 months to 21.75± 17.44 with insignificant difference (f=0.454, p=0.574). The mean score of problematic internet use shows highly statistically significant decrement in the study group between three period of time (pretest= 62.93, immediately post= 52.13, and post 3 months=52.70) with large effect size 0.78 (f=95.029, p<0.001), in compared to control group that showed insignificant no changes (pretest= 64.0±14.54, immediately post= 63.13±12.87, and post 3 months=63.53±11.36) with (f=1.012, p=0.332). In addition, the total mean score of psychological well-being was increased immediately after therapy and later for three months of therapy (pretest= 128.47, immediately post=148.77, and post 3 months= 153.60) with highly statistically significant (f=41.197, p<0.001) with effect size 0.85, compared to no change among control group (pretest=125.97±32.58, immediately post= 126.23±30.86, and post 3 months=126.43±29.78) with (f=0.208, p=0.698). Conclusion: Efficacy of distress tolerance skills intervention had been proven in altering poor psychological wellbeing among students with problematic internet use. It helps students to learn new skills and use more adaptive strategies to overcome distress tolerance difficulties.

Case report: Severe sinus tachycardia as a leading manifestation of systemic lupus erythematosus flare.

Systemic lupus erythematosus (SLE) is known to have various cardiac manifestations, including arrhythmias and tachycardia. However, it is rare to encounter severe sinus tachycardia as a presenting feature in patients with SLE. Herein, we present a case of a 32-year-old Filipino female with a history of recurrent hospital admissions due to palpitations and uncontrolled tachycardia. Despite trying various symptomatic treatments, her symptoms remained persistent. Ultimately, the patient was diagnosed with SLE during her hospital stay. Eventually, her symptoms improved after initiating steroids. In conclusion, severe sinus tachycardia could be an unusual presentation of SLE that physicians should consider.

Long-term safety and efficacy of pegunigalsidase alfa: A multicenter 6-year study in adult patients with Fabry disease.

PURPOSE: Fabry disease (FD) is a rare lysosomal storage disorder caused by pathogenic variants in the GLA gene encoding α-galactosidase (α-Gal)-A. We evaluated long-term safety/efficacy of pegunigalsidase alfa, a novel PEGylated α-Gal-A enzyme replacement therapy (ERT) now approved for FD. METHODS: In a phase-1/2 dose-ranging study, 15 ERT-naive adults with FD completed 12 months of pegunigalsidase alfa and enrolled in this 60-month open-label extension of 1 mg/kg pegunigalsidase alfa infusions every 2 weeks. RESULTS: Fifteen patients enrolled (8 males; 7 females); 10 completed ≥48 months (60 months total treatment), and 2 completed 60 months (72 months total treatment). During treatment, most treatment-emergent adverse events were mild/moderate in severity and all infusion-related reactions were mild/moderate in severity. Four patients were transiently positive for anti-pegunigalsidase alfa IgG. Patients showed continuous reduction in plasma lyso-Gb3 concentrations with mean (standard error) reduction of 76.1 [25.1] ng/mL from baseline to month 24. At 60 months, the estimated glomerular filtration rate slope was comparable to that observed in patients treated with other ERTs. Cardiac function assessments revealed stability; no cardiac fibrosis was observed. CONCLUSION: In this first long-term assessment of pegunigalsidase alfa administration in patients with FD, we found favorable safety/efficacy. Our data suggest long-term continuous benefits of pegunigalsidase alfa treatment in adults with FD.

Light-Driven Hydrogen Evolution Reaction Catalyzed by a Molybdenum-Copper Artificial Hydrogenase.

Orange protein (Orp) is a small bacterial metalloprotein of unknown function that harbors a unique molybdenum/copper (Mo/Cu) heterometallic cluster, [S2MoS2CuS2MoS2]3-. In this paper, the performance of Orp as a catalyst for the photocatalytic reduction of protons into H2 has been investigated under visible light irradiation. We report the complete biochemical and spectroscopic characterization of holo-Orp containing the [S2MoS2CuS2MoS2]3- cluster, with docking and molecular dynamics simulations suggesting a positively charged Arg, Lys-containing pocket as the binding site. Holo-Orp exhibits excellent photocatalytic activity, in the presence of ascorbate as the sacrificial electron donor and [Ru(bpy)3]Cl2 as the photosensitizer, for hydrogen evolution with a maximum turnover number of 890 after 4 h irradiation. Density functional theory (DFT) calculations were used to propose a consistent reaction mechanism in which the terminal sulfur atoms are playing a key role in promoting H2 formation. A series of dinuclear [S2MS2M'S2MS2](4n)- clusters, with M = MoVI, WVI and M'(n+) = CuI, FeI, NiI, CoI, ZnII, CdII were assembled in Orp, leading to different M/M'-Orp versions which are shown to display catalytic activity, with the Mo/Fe-Orp catalyst giving a remarkable turnover number (TON) of 1150 after 2.5 h reaction and an initial turnover frequency (TOF°) of 800 h-1 establishing a record among previously reported artificial hydrogenases.

Periocular management in recent facial palsy patients treated with triple innervation technique: A retrospective case series.

Facial paralysis decreases eye protection mechanisms leading to ocular problems up to corneal ulceration, and blindness. This study aimed to evaluate the outcomes of periocular procedures for recent facial paralysis. Medical records of patients with unilateral recent complete facial palsy who did periocular procedures at the Maxillofacial Surgery Department of San Paolo Hospital (Milan, Italy) between April 2018 and November 2021 were retrospectively reviewed. 26 patients were included. All patients were evaluated 4 months after surgery. The first group included 9 patients who underwent upper eye lid lipofilling and midface suspension with fascia lata graft; they had no ocular dryness symptoms and no need for eye protection measures in 33.3% of cases, significant reduction of ocular symptoms and need for eye protection measures in 66.6% of patient, 0-2 mm lagophthalmos in 66.6% and 3-4 mm lagophthalmos in 33.3%. The second group of 17 patients who underwent upper eyelid lipofilling, midface suspension with fascia lata graft and lateral tarsorrhaphy, had no ocular dryness symptoms and no need for eye protection measures in 17.6% of patient, significant reduction of ocular symptoms and need for eye protection measures in 76.4% of patient, 0-2 mm lagophthalmos in 70.5%, 3-4 mm lagophthalmos in 23.5% and one patient 5,8%had 8 mm lagophthalmos and persistent symptoms. No ocular complication, cosmetic complain or donner site morbidity were reported. Upper eyelid lipofilling, midface suspension with fascia lata graft and lateral tarsorrhaphy decrease ocular dryness symptoms and need for eye protection measures and improve lagophthalmos: the association of the reinnervation with these complementary techniques is therefore highly recommended in order to immediately protect the eye.