Subcutaneous immunoglobulin replacement therapy in patients with immunodeficiencies - impact of drug packaging and administration method on patient reported outcomes.

BACKGROUND: Here, the perspective of patients with primary and secondary immunodeficiency receiving subcutaneous immunoglobulin (SCIg) via introductory smaller size pre-filled syringes (PFS) or vials were compared. METHODS: An online survey was conducted in Canada by the Association des Patients Immunodéficients du Québec (APIQ) (10/2020-03/2021). Survey questions included: reasons for choosing SCIg packaging and administration methods, training experiences, infusion characteristics, and switching methods. The survey captured structured patient-reported outcomes: treatment satisfaction and its sub-domains, symptom state, general health perception, and physical and mental function. Respondents using PFS were compared with vial users, overall and stratified by their administration method (pump or manual push). RESULTS: Of the 132 total respondents, 66 respondents used vials, with 38 using a pump and 28 using manual push. PFS (5 and 10 mL sizes) were being used by 120 respondents, with 38 using a pump and 82 using manual push. PFS users were associated with a 17% lower median (interquartile range) SCIg dose (10 [8, 12] vs. 12 [9, 16] g/week, respectively), a significantly shorter infusion preparation time (15 [10, 20] vs. 15 [10, 30] mins, respectively), and a trend for shorter length of infusion (60 [35, 90] vs. 70 [48, 90] mins, respectively) compared with those on vials. Patient-reported treatment satisfaction scores were overall similar between vial and PFS users (including on the domains of effectiveness and convenience), except for a higher score for vials over PFS on the domain of global satisfaction (p=0.02). CONCLUSIONS: Consistent with prescribing that reflects a recognition of less wastage, PFS users were associated with a significantly lower SCIg dose compared with vial users. PFS users were also associated with shorter pre-infusion times, reflecting simpler administration mechanics compared with vial users. Higher global satisfaction with treatment among vial users compared with PFS users was consistent with users being limited to smaller PFS size options in Canada during the study period. Patient experience on PFS is expected to improve with the introduction of larger PFS sizes. Overall, treatment satisfaction for SCIg remains consistently high with the introduction of PFS packaging compared with vials.

Factors associated with poor sleep quality among construction workers in Arba Minch town, Ethiopia: A cross-sectional study.

Background and Aims: Sleep is critical for human physical and cognitive health. Even though poor sleep quality had a major negative impact on workers' health and safety, there is a scarcity of study that attempts to demonstrate its magnitude and causative factors in labor-intensive environments. Methods: A cross-sectional study design was employed. A total of 423 individuals were selected using a simple random sampling technique, starting from April 1, 2020 to May 1, 2020. Interviews were administered using the validated and pretested Pittsburgh Sleep Quality Index (PSQI) tool. EpiData version 4.4.3.1 was used for data entry and SPSS version 25 for analysis. To associate factors with poor sleep quality binary logistic regression model was fitted at 95% confidence interval (CI). A p < 0.25 and p < 0.05 were used to declare association in bivariable and multivariable analysis, respectively. Results: A total of 415 building construction workers take part in this study, with a response rate of 98.1%. A PSQI global score showed 66.3% (95% CI: [0.63, 0.71]) of construction workers suffering from poor sleep quality. Working hours, work experience, previous injury status, managerial support on occupational safety and health, cigarette smoking, and job satisfaction were the factors that were associated with poor sleep quality significantly. Conclusions: Two-thirds of construction workers suffer from poor sleep quality. Risk factors include shorter working years, longer working hours, prior injury, lack of managerial support, cigarette smoking, and low job satisfaction. Efficient health education and promotion through taking the identified associated factors into account could help reduce poor sleep quality.

The localization of centromere protein A is conserved among tissues.

Centromeres are epigenetically specified by the histone H3 variant CENP-A. Although mammalian centromeres are typically associated with satellite DNA, we previously demonstrated that the centromere of horse chromosome 11 (ECA11) is completely devoid of satellite DNA. We also showed that the localization of its CENP-A binding domain is not fixed but slides within an about 500 kb region in different individuals, giving rise to positional alleles. These epialleles are inherited as Mendelian traits but their position can move in one generation. It is still unknown whether centromere sliding occurs during meiosis or during development. Here, we first improve the sequence of the ECA11 centromeric region in the EquCab3.0 assembly. Then, to test whether centromere sliding may occur during development, we map the CENP-A binding domains of ECA11 using ChIP-seq in five tissues of different embryonic origin from the four horses of the equine FAANG (Functional Annotation of ANimal Genomes) consortium. Our results demonstrate that the centromere is localized in the same region in all tissues, suggesting that the position of the centromeric domain is maintained during development.

Polymorphisms in Maternal Selected Folate Metabolism-Related Genes in Neural Tube Defect-Affected Pregnancy.

Background: Neural tube defects (NTDs) are abnormalities of the brain and spinal cord, which occur as a result of failure in neural tube closure during embryogenesis. Causes of NTDs are complex and multiple, with hereditary, lifestyle, and environmental factors appearing to play a role. In spite of their impact on public health, the role genetics play on NTDs in Ethiopia is lacking. In this study, the role of polymorphisms in MTHFR 677C > T (rs1801133), MTHFR 1298A > C (rs1801131), MTRR 66A > G (rs1801394), RFC1 80A > G (rs1051266), and TCN2 776C > G (rs1801198) on the risk of having NTD-affected pregnancy was investigated. Materials and Methods: One hundred women with NTD-affected pregnancy and 100 women with normal pregnancy were included in the study. DNA was extracted from saliva and genotyping for five polymorphisms in four genes was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The departure of the genotype's distribution from Hardy-Weinberg equilibrium (HWE) was evaluated using the x2 goodness-of-fit test. Frequencies of genotypes and alleles in case and control mothers were determined and differences between relative frequencies were evaluated by the x2 or the Fisher's exact test. Results: The statistically significant difference was absent in the genotype and allele frequencies for all the analyzed polymorphisms between cases and controls (P > 0.05). Conclusion: MTHFR 677C > T, MTHFR 1298A > C, MTRR 66A > G, RFC1 80A > G, and TCN2 776C > G polymorphisms lack association with the risk of having a pregnancy affected by NTD. The role of other genes or environmental factors in NTD etiology needs to be investigated.

A Satellite-Free Centromere in Equus przewalskii Chromosome 10.

In mammals, centromeres are epigenetically specified by the histone H3 variant CENP-A and are typically associated with satellite DNA. We previously described the first example of a natural satellite-free centromere on Equus caballus chromosome 11 (ECA11) and, subsequently, on several chromosomes in other species of the genus Equus. We discovered that these satellite-free neocentromeres arose recently during evolution through centromere repositioning and/or chromosomal fusion, after inactivation of the ancestral centromere, where, in many cases, blocks of satellite sequences were maintained. Here, we investigated by FISH the chromosomal distribution of satellite DNA families in Equus przewalskii (EPR), demonstrating a good degree of conservation of the localization of the major horse satellite families 37cen and 2PI with the domestic horse. Moreover, we demonstrated, by ChIP-seq, that 37cen is the satellite bound by CENP-A and that the centromere of EPR10, the ortholog of ECA11, is devoid of satellite sequences. Our results confirm that these two species are closely related and that the event of centromere repositioning which gave rise to EPR10/ECA11 centromeres occurred in the common ancestor, before the separation of the two horse lineages.

Remote sensing of savanna woody species diversity: A systematic review of data types and assessment methods.

Despite savannas being known for their relatively sparse vegetation coverage compared to other vegetation ecosystems, they harbour functionally diverse vegetation forms. Savannas are affected by climate variability and anthropogenic factors, resulting in changes in woody plant species compositions. Monitoring woody plant species diversity is therefore important to inform sustainable biodiversity management. Remote sensing techniques are used as an alternative approach to labour-intensive field-based inventories, to assess savanna biodiversity. The aim of this paper is to review studies that applied remote sensing to assess woody plant species diversity in savanna environments. The paper first provides a brief account of the spatial distribution of savanna environments around the globe. Thereafter, it briefly defines categorical classification and continuous-scale species diversity assessment approaches for savanna woody plant estimation. The core review section divides previous remote sensing studies into categorical classification and continuous-scale assessment approaches. Within each division, optical, Radio Detection And Ranging (RADAR) and Light Detection and Ranging (LiDAR) remote sensing as applied to savanna woody species diversity is reviewed. This is followed by a discussion on multi-sensor applications to estimate woody plant species diversity in savanna. We recommend that future research efforts should focus strongly on routine application of optical, RADAR and LiDAR remote sensing of physiologically similar woody plant species in savannas, as well as on extending these methodological approaches to other vegetation environments.

ECFS standards of care on CFTR-related disorders: Diagnostic criteria of CFTR dysfunction.

The spectrum of disorders involving CFTR (cystic fibrosis transmembrane conductance regulator) dysfunction correlates with a continuous gradient of CFTR function defined by the combination of two allelic CFTR variants. CFTR-related disorders are clinical entities with features of cystic fibrosis (CF) and evidence for presence of CFTR dysfunction but not meeting criteria for diagnosis of CF. Individuals with CFTR-RDs demonstrate a wide range of CFTR activity and are still under-recognized or misclassified. The level of CFTR dysfunction may be measured in vivo (sweat testing, nasal potential difference measurements) and/or by ex vivo tests (intestinal current measurement), or indirectly indicated by CFTR variants, as alteration in sequence of the CFTR gene translates into CFTR dysfunction. CFTR bioassays can aid in the diagnosis of individuals with CF, but we lack parameters to differentiate CF from CFTR-RD. In the era of the CFTR modulators and their potential clinical benefit, it is of utmost importance to diagnose CFTR-RD as unambiguously as possible. We therefore propose the following to define compatible CFTR dysfunction in a person with a suspected diagnosis of CFTR-RD : (1) evidence of CFTR dysfunction in vivo or ex vivo in at least two different CFTR functional test types, or (2) One CFTR variant known to reduce CFTR function and evidence of CFTR dysfunction in vivo or ex vivo in at least two different CFTR functional test types, or (3) Two CFTR variants shown to reduce CFTR function, with at most one CF-causing variant.

Acute mesenteric ischemia: updated guidelines of the World Society of Emergency Surgery.

Acute mesenteric ischemia (AMI) is a group of diseases characterized by an interruption of the blood supply to varying portions of the intestine, leading to ischemia and secondary inflammatory changes. If untreated, this process may progress to life-threatening intestinal necrosis. The incidence is low, estimated at 0.09-0.2% of all acute surgical admissions, but increases with age. Although the entity is an uncommon cause of abdominal pain, diligence is required because if untreated, mortality remains in the range of 50%. Early diagnosis and timely surgical intervention are the cornerstones of modern treatment to reduce the high mortality associated with this entity. The advent of endovascular approaches in parallel with modern imaging techniques is evolving and provides new treatment options. Lastly, a focused multidisciplinary approach based on early diagnosis and individualized treatment is essential. Thus, we believe that updated guidelines from World Society of Emergency Surgery are warranted, in order to provide the most recent and practical recommendations for diagnosis and treatment of AMI.

Robertsonian Fusion and Centromere Repositioning Contributed to the Formation of Satellite-free Centromeres During the Evolution of Zebras.

Centromeres are epigenetically specified by the histone H3 variant CENP-A and typically associated with highly repetitive satellite DNA. We previously discovered natural satellite-free neocentromeres in Equus caballus and Equus asinus. Here, through ChIP-seq with an anti-CENP-A antibody, we found an extraordinarily high number of centromeres lacking satellite DNA in the zebras Equus burchelli (15 of 22) and Equus grevyi (13 of 23), demonstrating that the absence of satellite DNA at the majority of centromeres is compatible with genome stability and species survival and challenging the role of satellite DNA in centromere function. Nine satellite-free centromeres are shared between the two species in agreement with their recent separation. We assembled all centromeric regions and improved the reference genome of E. burchelli. Sequence analysis of the CENP-A binding domains revealed that they are LINE-1 and AT-rich with four of them showing DNA amplification. In the two zebras, satellite-free centromeres emerged from centromere repositioning or following Robertsonian fusion. In five chromosomes, the centromeric function arose near the fusion points, which are located within regions marked by traces of ancestral pericentromeric sequences. Therefore, besides centromere repositioning, Robertsonian fusions are an important source of satellite-free centromeres during evolution. Finally, in one case, a satellite-free centromere was seeded on an inversion breakpoint. At 11 chromosomes, whose primary constrictions seemed to be associated with satellite repeats by cytogenetic analysis, satellite-free neocentromeres were instead located near the ancestral inactivated satellite-based centromeres; therefore, the centromeric function has shifted away from a satellite repeat containing locus to a satellite-free new position.

Hypertriglyceridaemia in adolescents may have serious complications.

Acute pancreatitis is an often-overlooked cause of acute abdominal pain in children and adolescents. Severe hypertriglyceridaemia is an important cause of recurrent acute pancreatitis. Monogenic causes of hypertriglyceridaemia, such as familial chylomicronaemia caused by lipoprotein lipase deficiency, are more frequently encountered in children and adolescents, but remain rare. Polygenic hypertriglyceridaemia is more common, but may require a precipitant before manifesting. With the global increase in obesity and type 2 diabetes, secondary causes of hypertriglyceridaemia in children and adolescents are increasing. We report two cases of severe hypertriglyceridaemia and pancreatitis in adolescent females. Hypertriglyceridaemia improved markedly with restriction of dietary fat. An inhibitor to lipoprotein lipase was found to be the cause in one patient, while in the other limited genetic investigation excluded chylomicronaemia owing to deficiency of lipoprotein lipase, its activators and processing proteins.

Molecular Dynamics and Evolution of Centromeres in the Genus Equus.

The centromere is the chromosomal locus essential for proper chromosome segregation. While the centromeric function is well conserved and epigenetically specified, centromeric DNA sequences are typically composed of satellite DNA and represent the most rapidly evolving sequences in eukaryotic genomes. The presence of satellite sequences at centromeres hampered the comprehensive molecular analysis of these enigmatic loci. The discovery of functional centromeres completely devoid of satellite repetitions and fixed in some animal and plant species represented a turning point in centromere biology, definitively proving the epigenetic nature of the centromere. The first satellite-free centromere, fixed in a vertebrate species, was discovered in the horse. Later, an extraordinary number of satellite-free neocentromeres had been discovered in other species of the genus Equus, which remains the only mammalian genus with numerous satellite-free centromeres described thus far. These neocentromeres arose recently during evolution and are caught in a stage of incomplete maturation. Their presence made the equids a unique model for investigating, at molecular level, the minimal requirements for centromere seeding and evolution. This model system provided new insights on how centromeres are established and transmitted to the progeny and on the role of satellite DNA in different aspects of centromere biology.

Assessing the effect of sustainable land management on improving water security in the Blue Nile Highlands: a paired catchment approach.

The Blue Nile Highlands, Ethiopia, has been experiencing serious land degradation, menacing water security, and then human well-being. However, sustainable land management (SLM) may be the way to curb land degradation and improve water security. Therefore, in order to assess benefits after a 5-year catchment restoration effort, we conducted a paired-catchment study to investigate runoff and soil moisture dynamics. First and second catchments were used as control and treated, respectively. After comparing observations gathered from four sites within each of the study catchments, we found that implementing SLM reduced runoff curve numbers by -13.9 to -21.6 units and increased soil moisture storage by 15.6 to 800%, then promoting rapid recovery of the hydrologic functionality of the natural landscapes. We conclude that SLM initiatives can greatly improve water security in the drought-prone Blue Nile Highlands.

Telomeric-Like Repeats Flanked by Sequences Retrotranscribed from the Telomerase RNA Inserted at DNA Double-Strand Break Sites during Vertebrate Genome Evolution.

Interstitial telomeric sequences (ITSs) are stretches of telomeric-like repeats located at internal chromosomal sites. We previously demonstrated that ITSs have been inserted during the repair of DNA double-strand breaks in the course of evolution and that some rodent ITSs, called TERC-ITSs, are flanked by fragments retrotranscribed from the telomerase RNA component (TERC). In this work, we carried out an extensive search of TERC-ITSs in 30 vertebrate genomes and identified 41 such loci in 22 species, including in humans and other primates. The fragment retrotranscribed from the TERC RNA varies in different lineages and its sequence seems to be related to the organization of TERC. Through comparative analysis of TERC-ITSs with orthologous empty loci, we demonstrated that, at each locus, the TERC-like sequence and the ITS have been inserted in one step in the course of evolution. Our findings suggest that telomerase participated in a peculiar pathway of DNA double-strand break repair involving retrotranscription of its RNA component and that this mechanism may be active in all vertebrate species. These results add new evidence to the hypothesis that RNA-templated DNA repair mechanisms are active in vertebrate cells.

Evaluating the data quality of the Gazepoint GP3 low-cost eye tracker when used independently by study participants.

The portability of low-cost eye trackers makes them attractive for research outside of the laboratory. Such research may require independent eye-tracker use. The present work compared the data quality of the Gazepoint GP3 when used independently by research participants with expert eye-tracking users. Twenty participants completed a training and a testing session 1 week apart. At training visits, participants were taught how to set up and use eye-tracking hardware and software and how to complete two tasks: a calibration task to measure accuracy and precision, as well as a visual search task to assess target fixations. At the testing session, participants set up the Gazepoint eye tracker and completed the two tasks without assistance. Participant accuracy and precision and visual search performance were compared to values obtained from two expert eye-tracking users. Additionally, the eye-tracker sampling rate, which is sensitive to factors such as head motion, was assessed in both participants and the expert users. Participant accuracy and precision closely approximated expert user values. Participant target fixations were detected with a 92.5% sensitivity and 76.8% specificity, closely mirroring expert user sensitivity and specificity. The sampling rate distribution was also similar between the participants and expert user (the means of those distributions were 16.99 ± 3.0 ms and 16.43 ± 2.3 ms, respectively). When used independently, data quality obtained from a low-cost, portable eye-tracking setup closely approximated values obtained from an expert user and was adequate enough to be a feasible option for some studies that require independent use by study participants.

Deposition of PFAS 'forever chemicals' on Mt. Everest.

Mt. Everest, one of the most coveted climbing mountains on earth, also contains the highest altitude chemical contamination on land. For the first time, meltwater and snow samples from Mt. Everest's Khumbu Glacier were analyzed for "forever chemicals" per- and polyfluoroalkyl substances (PFAS). Our research team utilized solid-phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify pollutants sampled from Everest Base Camp, Camp 1, Camp 2, and Everest Balcony. From the 14 PFAS compounds tested for, we found perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexanoic acid (PFHxA) in Mt. Everest snow and meltwater. The highest concentrations found were 26.14 ng/L and 10.34 ng/L PFOS at Base Camp and Camp 2, respectively. However, PFAS species were seen within 1-2 orders of magnitude in all sampling sites with detection, potentially suggesting a widespread presence on the mountain. Our samples are the highest altitude PFAS samples ever retrieved and indicate the need for further sampling both on Mt. Everest and in the below-glacier watershed.

Dinucleosome specificity and allosteric switch of the ISW1a ATP-dependent chromatin remodeler in transcription regulation.

Over the last 3 decades ATP-dependent chromatin remodelers have been thought to recognize chromatin at the level of single nucleosomes rather than higher-order organization of more than one nucleosome. We show the yeast ISW1a remodeler has such higher-order structural specificity, as manifested by large allosteric changes that activate the nucleosome remodeling and spacing activities of ISW1a when bound to dinucleosomes. Although the ATPase domain of Isw1 docks at the SHL2 position when ISW1a is bound to either mono- or di-nucleosomes, there are major differences in the interactions of the catalytic subunit Isw1 with the acidic pocket of nucleosomes and the accessory subunit Ioc3 with nucleosomal DNA. By mutational analysis and uncoupling of ISW1a's dinucleosome specificity, we find that dinucleosome recognition is required by ISW1a for proper chromatin organization at promoters; as well as transcription regulation in combination with the histone acetyltransferase NuA4 and histone H2A.Z exchanger SWR1.

Efficiency of microvascular free flap reconstructive surgery: An observational study.

OBJECTIVE: We aimed to assess operative workflow and efficiency in microvascular free flaps via a direct observational study based on Lean principles of quality improvement (QI). METHODS: Observers monitored the workflow of twenty-three free flaps. Pre-operative preparation and surgical duration was recorded with supplemental data provided from our institution's surgical tracking database. Traffic patterns of operating room (OR) staff were documented as "entries" and "exits" from the OR and classified by role and the reason that the entry or exit was required. Patient data was obtained via chart review. RESULTS: The mean surgical time was 9.0 h. Approximately 20% of OR time was dedicated to the pre-incision process, averaging 1.6 h per case. One third of entries and exits occurred during this period. In total, 180.2 surgical hours were observed during which 6215 "entries" and "exits" occurred. The mean number of entries and exits per case was 270; the most common reasons were supplies and communication. No association was observed between elapsed surgical time or total number of entries and exits with post-operative infection rates. CONCLUSION: Comprehensive observational workflow studies of free flaps are challenging to execute due to lengthy procedure times. At our high-volume institution, a significant portion of OR time is devoted to the pre-incision period, largely due to inadequate supply availability and pre-operative communication. These findings will serve as a foundation for QI interventions at our institution, while our observational model provides a broadly applicable framework for assessing surgical efficiency.

Tracking conservation effectiveness in the Vhembe Biosphere Reserve in South Africa using Landsat imagery.

Biosphere reserves (BRs) seek to reconcile a sustainable relationship between human welfare and environmental integrity by adopting a landscape model that distinguishes between three interdependent management zones (core, buffer, transition). Considering the increasing human influence on landscapes in BRs, the tracking land use-land cover (LULC) dynamics is crucial for the development and planning of efficient management strategies for specific management zone. This study aimed at (i) assessing biodiversity protection around the core zones to highlight the threats facing the core zones and (ii) tracking the effect of the proclamation of the Vhembe Biosphere Reserve (VBR) on the LULC dynamics in the management zones through spatio-temporal analysis using Landsat imagery acquired from1999 to 2018. Six LULC categories (water body, forest/bush, shrubs/grass, agricultural land, bare soil, and built-up/mines) were identified and mapped using the support vector machine (SVM) classification to address both objectives. Assessment of threats around the core zones using artificial buffers (0-5, 10-15, and 15-20 km radius) created around them showed agricultural activities in the most immediate buffers (0-5 km radius). The LULC dynamics showed vegetation increase in all the management zones evidenced by the reduction of bare soil as well shrub/grass lands, and by the corresponding increase in foliage-richer forest/bush lands since the proclamation of the reserve in 2009. The findings might signify a positive outcome of vegetation increase as a consequence of the proclamation of the VBR. However, firmer conservation measures must be adopted and priority must be given to the arrangement of the management zones to strengthen biodiversity protection in the core zone.

Estimation of woody plant species diversity during a dry season in a savanna environment using the spectral and textural information derived from WorldView-2 imagery.

Remote sensing techniques are useful in the monitoring of woody plant species diversity in different environments including in savanna vegetation types. However, the performance of satellite imagery in assessing woody plant species diversity in dry seasons has been understudied. This study aimed to assess the performance of multiple Gray Level Co-occurrence Matrices (GLCM) derived from individual bands of WorldView-2 satellite imagery to quantify woody plant species diversity in a savanna environment during the dry season. Woody plant species were counted in 220 plots (20 m radius) and subsequently converted to a continuous scale of the Shannon species diversity index. The index regressed against the GLCMs using the all-possible-subsets regression approach that builds competing models to choose from. Entropy GLCM yielded the best overall accuracy (adjusted R2: 0.41-0.46; Root Mean Square Error (RMSE): 0.60-0.58) in estimating species diversity. The effect of the number of predicting bands on species diversity estimation was also explored. Accuracy generally increased when three-five bands were used in models but stabilised or gradually decreased as more than five bands were used. Despite the peak accuracies achieved with three-five bands, performances still fared well for models that used fewer bands, showing the relevance of few bands for species diversity estimation. We also assessed the effect of GLCM window size (3×3, 5×5 and 7×7) on species diversity estimation and generally found inconsistent conclusions. These findings demonstrate the capability of GLCMs combined with high spatial resolution imagery in estimating woody plants species diversity in a savanna environment during the dry period. It is important to test the performance of species diversity estimation of similar environmental set-ups using widely available moderate-resolution imagery.