Polar localization of a rice silicon transporter requires isoleucine at both C- and N-termini as well as positively charged residues.

Silicon (Si) is important for stable and high yields in rice (Oryza sativa), a typical Si hyperaccumulator. The high Si accumulation is achieved by the cooperation of 2 Si transporters, LOW SILICON 1 (OsLsi1) and OsLsi2, which are polarly localized in cells of the root exodermis and endodermis. However, the mechanism underlying their polar localization is unknown. Here, we identified amino acid residues critical for the polar localization of OsLsi1. Deletion of both N- and C-terminal regions resulted in the loss of its polar localization. Furthermore, the deletion of the C-terminus inhibited its trafficking from the endoplasmic reticulum to the plasma membrane. Detailed site-directed mutagenesis analysis showed that Ile18 at the N-terminal region and Ile285 at the C-terminal region were essential for the polar localization of OsLsi1. Moreover, a cluster of positively charged residues at the C-terminal region is also required for polar localization. Phosphorylation and Lys modifications of OsLsi1 are unlikely to be involved in its polar localization. Finally, we showed that the polar localization of OsLsi1 is required for the efficient uptake of Si. Our study not only identified critical residues required for the polar localization of OsLsi1, but also provided experimental evidence for the importance of transporter polarity for efficient nutrient uptake.

Local distribution of manganese to leaf sheath is mediated by OsNramp5 in rice.

To play essential roles of manganese (Mn) in plant growth and development, it needs to be transported to different organs and tissues after uptake. However, the molecular mechanisms underlying Mn distribution between different tissues are poorly understood. We functionally characterized a member of rice natural resistance-associated macrophage protein (NRAMP) family, OsNramp5 in terms of its tissue specificity of gene expression, cell-specificity of protein localization, phenotypic analysis of leaf growth and response to Mn fluctuations. OsNramp5 is highly expressed in the leaf sheath. Immunostaining revealed that OsNramp5 is polarly localized at the proximal side of xylem parenchyma cells of the leaf sheath. Both the gene expression and protein abundance of OsNramp5 are unaffected by different Mn concentrations. Knockout of OsNramp5 decreased the distribution of Mn to the leaf sheath, but increased the distribution to the leaf blade at both low and high Mn supplies, resulting in reduced growth of leaf sheath. Furthermore, expression of OsNramp5 under the control of root-specific promoter in osnramp5 mutant complemented Mn uptake, but could not complement Mn distribution to the leaf sheath. These results indicate that OsNramp5 expressed in the leaf sheath plays an important role in unloading Mn from the xylem for the local distribution in rice.

Boron uptake in rice is regulated post-translationally via a clathrin-independent pathway.

Uptake of boron (B) in rice (Oryza sativa) is mediated by the Low silicon rice 1 (OsLsi1) channel, belonging to the NOD26-like intrinsic protein III subgroup, and the efflux transporter B transporter 1 (OsBOR1). However, it is unknown how these transporters cooperate for B uptake and how they are regulated in response to B fluctuations. Here, we examined the response of these two transporters to environmental B changes at the transcriptional and posttranslational level. OsBOR1 showed polar localization at the proximal side of both the exodermis and endodermis of mature root region, forming an efficient uptake system with OsLsi1 polarly localized at the distal side of the same cell layers. Expression of OsBOR1 and OsLsi1 was unaffected by B deficiency and excess. However, although OsLsi1 protein did not respond to high B at the protein level, OsBOR1 was degraded in response to high B within hours, which was accompanied with a significant decrease of total B uptake. The high B-induced degradation of OsBOR1 was inhibited in the presence of MG-132, a proteasome inhibitor, without disturbance of the polar localization. In contrast, neither the high B-induced degradation of OsBOR1 nor its polarity was affected by induced expression of dominant-negative mutated dynamin-related protein 1A (OsDRP1AK47A) or knockout of the mu subunit (AP2M) of adaptor protein-2 complex, suggesting that clathrin-mediated endocytosis is not involved in OsBOR1 degradation and polar localization. These results indicate that, in contrast to Arabidopsis thaliana, rice has a distinct regulatory mechanism for B uptake through clathrin-independent degradation of OsBOR1 in response to high B.

Advanced emergency braking system reduces the risk of motor vehicle collisions caused by falling asleep while driving in patients with untreated obstructive sleep apnea.

Obstructive sleep apnea leads to excessive daytime sleepiness and cognitive dysfunction, which are risk factors for motor vehicle collisions. We aimed to clarify if vehicles with an advanced emergency braking system could reduce motor vehicle collisions caused by falling asleep while driving among patients with untreated obstructive sleep apnea. We enrolled patients with untreated obstructive sleep apnea who underwent polysomnography. The questionnaires included the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, history of drowsy driving accidents, and use of an advanced emergency braking system. Multivariate analysis was performed, and odds ratios and 95% confidence intervals were calculated. This study included 1097 patients (mean age, 51.2 ± 12.9 years). Collisions caused by falling asleep while driving were recorded in 59 (5.4%) patients, and were more frequently observed in vehicles without an advanced emergency braking system (p = 0.045). Multivariate analysis showed that these collisions were associated with use of an advanced emergency braking system (odds ratio [95% confidence interval]: 0.39 [0.16-0.97], p = 0.04), length of driving (2.79 [1.19-6.50], p = 0.02), total sleep time (2.40 [1.62-3.55], p < 0.0001), sleep efficiency (0.94 [0.90-0.98], p = 0.003) and periodic limb movement index (1.02 [1.01-1.03], p = 0.004). The collision risk caused by falling asleep while driving in vehicles with an advanced emergency braking system was significantly lower. This study indicates that advanced emergency braking systems may be a preventive measure to reduce motor vehicle collisions among patients with untreated obstructive sleep apnea.

Cell-Type-Dependent but CME-Independent Polar Localization of Silicon Transporters in Rice.

Silicon (Si) is an important nutrient required for sustainable and high production of rice and its uptake is mediated by a pair of influx (OsLsi1)-efflux (OsLsi2) transporters showing polar localization. However, the mechanisms underlying their polarity are unknown. Here, we revealed that the polarity of the Si transporters depends on cell types. The polar localization of both OsLsi1 and OsLsi2 was not altered by Si supply, but their protein abundance was reduced. Double immunostaining showed that localization of OsLsi1 and OsLsi2 was separated at the edge of the lateral polar domain by Casparian strips in the endodermis, whereas they were slightly overlapped at the transversal side of the exodermis. When OsLsi1 was ectopically expressed in the shoots, it showed polar localization at the xylem parenchyma cells of the basal node and leaf sheath, but not at the phloem companion cells. Ectopic expression of non-polar Si transporters, barley HvLsi2 and maize ZmLsi2 in rice, resulted in their polar localization at the proximal side. The polar localization of OsLsi1 and OsLsi2 was not altered by inhibition of clathrin-mediated endocytosis (CME) by dominant-negative induction of dynamin-related protein1A and knockout of mu subunit of adaptor protein 2 complex, although the knockout mutants of OsAP2M gene showed dwarf phenotype. These results indicate that CME is not required for the polar localization of Si transporters. Taken together, our results indicate that CME-independent machinery controls the polar localization of Si transporters in exodermis, endodermis of root cells and xylem parenchyma cells.

A pericycle-localized silicon transporter for efficient xylem loading in rice.

Rice is able to accumulate high concentrations of silicon (Si) in the shoots, and this ability is required for the mitigation of abiotic and biotic stresses. Although transporters for Si uptake have been identified, a transporter for the xylem loading of Si has not been found. We functionally characterized a Si transporter, OsLsi3, in terms of tissue-specific localization, knockout line phenotype and mathematic simulation. OsLsi3 was shown to be an efflux Si transporter. OsLsi3 was mainly expressed in the mature root region, and its expression was downregulated by Si. Immunostaining with a specific antibody showed that OsLsi3 was localized to the pericycle in the roots, without polarity. However, when it was expressed under the control of the OsLsi2 promoter, OsLsi3 became polarly localized to the proximal side of both the exodermis and endodermis. Knockout of this gene resulted in decreased Si uptake and concentration in the xylem sap under low Si supply, but not under high Si supply. Mathematical modeling showed that localization of OsLsi3 to the pericycle accounts for c. 30% of the total Si loading to the xylem under low Si concentrations. In summary, OsLsi3 was involved in the xylem loading of Si in rice roots, which is required for the efficient root-to-shoot translocation of Si.

Estimated respiratory arousal threshold in patients with rapid eye movement obstructive sleep apnea.

PURPOSE: Rapid eye movement (REM) obstructive sleep apnea (OSA) is a prevalent clinical phenotype. However, the literature focusing on the pathophysiology of REM OSA is limited. This study compared the proportion of individuals with a low respiratory arousal threshold between patients with REM and non-REM OSA. METHODS: REM OSA was defined as having an apnea-hypopnea index (AHI) ≥ 5 and AHI during REM (AHI-REM)/AHI during NREM (AHI-NREM) ≥ 2. REM OSA was sub-divided into REM-predominant OSA and REM-isolated OSA. REM-predominant OSA was defined as satisfying the definition of REM OSA and having an AHI-NREM ≥ 5. REM-isolated OSA was defined as satisfying the definition of REM OSA and having an AHI-NREM < 5. Patients with an AHI-REM/AHI-NREM < 2 were defined as having non-REM OSA. A low respiratory arousal threshold was defined as having 2 or more of the following conditions: AHI < 30 events/h, proportion of hypopnea > 58.3%, and nadir SpO2 > 82.5%. RESULTS: The proportions of individuals with low respiratory arousal thresholds among individuals with REM-predominant OSA and REM-isolated OSA were significantly higher (77.2% and 93.7%, respectively) than that of patients with non-REM OSA (48.6%). This was also true when the analysis was performed according to sex. CONCLUSION: These results indicate that a low respiratory arousal threshold might be an important endotype that contributes to the pathogenesis of REM OSA, especially in REM-isolated OSA.

Three polarly localized ammonium transporter 1 members are cooperatively responsible for ammonium uptake in rice under low ammonium condition.

Ammonium is a preferential nitrogen form for rice (Oryza sativa) grown in paddy field, but the molecular mechanisms for ammonium uptake have not been well understood. We functionally characterized three members belonging to ammonium transporter 1 (AMT1) and investigated their contributions to ammonium uptake. Spatial expression analysis showed that the upregulated expression of OsAMT1;1 and OsAMT1;2 and downregulated expression of OsAMT1;3 by ammonium were higher in the root mature region than in the root tips. All OsAMT1 members were polarly localized at the distal side of exodermis in the mature region of crown roots and lateral roots. Upon exposure to ammonium, localization of OsAMT1;1 and OsAMT1;2 was also observed in the endoplasmic reticulum, but their abundance in the plasma membrane was not changed. Single knockout of either gene did not affect ammonium uptake, but knockout of all three genes resulted in 95% reduction of ammonium uptake. However, the nitrogen uptake did not differ between the wild-type rice and triple mutants at high ammonium and nitrate supply. Our results indicate that three OsAMT1 members are cooperatively required for uptake of low ammonium in rice roots and that they undergo a distinct regulatory mechanism in response to ammonium.

Overexpression of the manganese/cadmium transporter OsNRAMP5 reduces cadmium accumulation in rice grain.

Rice is a major dietary source of the toxic metal cadmium (Cd), and reducing its accumulation in the grain is therefore important for food safety. We selected two cultivars with contrasting Cd accumulation and generated transgenic lines overexpressing OsNRAMP5, which encodes a major influx transporter for manganese (Mn) and Cd. We used two different promoters to control the expression, namely OsActin1 and maize Ubiquitin. Overexpression of OsNRAMP5 increased Cd and Mn uptake into the roots, but markedly decreased Cd accumulation in the shoots, whilst having a relatively small effect on Mn accumulation in the shoots. The overexpressed OsNRAMP5 protein was localized to the plasma membrane of all cell types in the root tips and lateral root primordia without polarity. Synchrotron X-ray fluorescence mapping showed that the overexpression lines accumulated more Cd in the root tips and lateral root primordia compared with the wild-type. When grown in three Cd-contaminated paddy soils, overexpression of OsNRAMP5 decreased concentration of Cd in the grain by 49-94% compared with the wild type. OsNRAMP5-overexpression plants had decreased Cd translocation from roots to shoots as a result of disruption of its radial transport into the stele for xylem loading, demonstrating the effect of transporter localization and polarity on ion homeostasis.

The urea transporter DUR3 contributes to rice production under nitrogen-deficient and field conditions.

Nitrogen is one of the most important elements for plant growth, and urea is one of the most frequently used nitrogen fertilizers worldwide. Besides the exogenously-supplied urea to the soil, urea is endogenously synthesized during secondary nitrogen metabolism. Here, we investigated the contribution of a urea transporter, DUR3, to rice production using a reverse genetic approach combined with localization studies. Tos17 insertion lines for DUR3 showed a 50% yield reduction in hydroponic culture, and a 26.2% yield reduction in a paddy field, because of decreased grain filling. Because shoot biomass production and shoot total N was not reduced, insertion lines were disordered not only in nitrogen acquisition but also in nitrogen allocation. During seed development, DUR3 insertion lines accumulated nitrogen in leaves and could not sufficiently develop their panicles, although shoot and root dry weights were not significantly different from the wild-type. The urea concentration in old leaf harvested from DUR3 insertion lines was lower than that in wild-type. DUR3 promoter-dependent ß-glucuronidase (GUS) activity was localized in vascular tissue and the midribs of old leaves. These results indicate that DUR3 contributes to nitrogen translocation and rice yield under nitrogen-deficient and field conditions.

Cytosolic Glutamine Synthetase Isozymes Play Redundant Roles in Ammonium Assimilation Under Low-Ammonium Conditions in Roots of Arabidopsis thaliana.

Ammonium is a major nitrogen source for plants; it is assimilated into glutamine via a reaction catalyzed by glutamine synthetase (GLN). Arabidopsis expresses four cytosolic GLN genes, GLN1; 1, GLN1; 2, GLN1; 3 and GLN1; 4, in roots. However, the function and organization of these GLN1 isozymes in ammonium assimilation in roots remain unclear. In this study, we aimed to characterize the four GLN1 isozymes. The levels of growth of the wild type and gln1 single and multiple knockout lines were compared in a hydroponic culture at ammonium concentrations of 0.1 and 3 mM. Under the low-ammonium concentration, in single mutants for each GLN1 gene, there was little effect on growth, whereas the triple mutant for GLN1; 1, GLN1; 2 and GLN1; 3 grew slowly and accumulated ammonium. Under the high-ammonium concentration, the single mutant for GLN1; 2 showed 50% decreases in fresh weight and glutamine, whereas the other gln1 single mutants did not show notable changes in the phenotype. The double mutant for GLN1; 1 and GLN1; 2 showed less growth and a lower glutamine concentration than the single mutant for GLN1; 2. Promoter analysis indicated an overlapping expression of GLN1; 1 with GLN1; 2 in the surface layers of the roots. We thus concluded that: (i) at a low concentration, ammonium was assimilated by GLN1; 1, GLN1; 2 and GLN1; 3, and they were redundant; (ii) low-affinity GLN1; 2 could contribute to ammonium assimilation at concentrations ranging from 0.1 to 3 mM; and (iii) GLN1; 1 supported GLN1; 2 within the outer cell layers of the root.

Decreasing arsenic accumulation in rice by overexpressing OsNIP1;1 and OsNIP3;3 through disrupting arsenite radial transport in roots.

Rice is a major dietary source of the toxic metalloid arsenic. Reducing arsenic accumulation in rice grain is important for food safety. We generated transgenic rice overexpressing two aquaporin genes, OsNIP1;1 and OsNIP3;3, under the control of a maize ubiquitin promoter or the rice OsLsi1 promoter, and tested the effect on arsenite uptake and translocation. OsNIP1;1 and OsNIP3;3 were highly permeable to arsenite in Xenopus oocyte assays. Both transporters were localized at the plasma membrane. Knockout of either gene had little effect on arsenite uptake or translocation. Overexpression of OsNIP1;1 or OsNIP3;3 in rice did not affect arsenite uptake but decreased root-to-shoot translocation of arsenite and shoot arsenic concentration markedly. The overexpressed OsNIP1;1 and OsNIP3;3 proteins were localized in all root cells without polarity. Expression of OsNIP1;1 driven by the OsLsi1 promoter produced similar effects. When grown in two arsenic-contaminated paddy soils, overexpressing lines contained significantly lower arsenic concentration in rice grain than the wild-type without compromising plant growth or the accumulation of essential nutrients. Overexpression of OsNIP1;1 or OsNIP3;3 provides a route for arsenite to leak out of the stele, thus restricting arsenite loading into the xylem. This strategy is effective in reducing arsenic accumulation in rice grain.

Contributions of two cytosolic glutamine synthetase isozymes to ammonium assimilation in Arabidopsis roots.

Glutamine synthetase (GS) catalyzes a reaction that incorporates ammonium into glutamate and yields glutamine in the cytosol and chloroplasts. Although the enzymatic characteristics of the GS1 isozymes are well known, their physiological functions in ammonium assimilation and regulation in roots remain unclear. In this study we show evidence that two cytosolic GS1 isozymes (GLN1;2 and GLN1;3) contribute to ammonium assimilation in Arabidopsis roots. Arabidopsis T-DNA insertion lines for GLN1;2 and GLN1;3 (i.e. gln1;2 and gln1;3 single-mutants), the gln1;2:gln1;3 double-mutant, and the wild-type accession (Col-0) were grown in hydroponic culture with variable concentrations of ammonium to compare their growth, and their content of nitrogen, carbon, ammonium, and amino acids. GLN1;2 and GLN1;3 promoter-dependent green fluorescent protein was observed under conditions with or without ammonium supply. Loss of GLN1;2 caused significant suppression of plant growth and glutamine biosynthesis under ammonium-replete conditions. In contrast, loss of GLN1;3 caused slight defects in growth and Gln biosynthesis that were only visible based on a comparison of the gln1;2 single- and gln1;2:gln1;3 double-mutants. GLN1;2, being the most abundantly expressed GS1 isozyme, markedly increased following ammonium supply and its promoter activity was localized at the cortex and epidermis, while GLN1;3 showed only low expression at the pericycle, suggesting their different physiological contributions to ammonium assimilation in roots. The GLN1;2 promoter-deletion analysis identified regulatory sequences required for controlling ammonium-responsive gene expression of GLN1;2 in Arabidopsis roots. These results shed light on GLN1 isozyme-specific regulatory mechanisms in Arabidopsis that allow adaptation to an ammonium-replete environment.

Asparagine synthetase1, but not asparagine synthetase2, is responsible for the biosynthesis of asparagine following the supply of ammonium to rice roots.

Asparagine is synthesized from glutamine by the reaction of asparagine synthetase (AS) and is the major nitrogen form in both xylem and phloem sap in rice (Oryza sativa L.). There are two genes encoding AS, OsAS1 and OsAS2, in rice, but the functions of individual AS isoenzymes are largely unknown. Cell type- and NH4(+)-inducible expression of OsAS1 as well as analyses of knockout mutants were carried out in this study to characterize AS1. OsAS1 was mainly expressed in the roots, with in situ hybridization showing that the corresponding mRNA was specifically accumulated in the three cell layers of the root surface (epidermis, exodermis and sclerenchyma) in an NH4(+)-dependent manner. Conversely, OsAS2 mRNA was abundant in leaf blades and sheathes of rice. Although OsAS2 mRNA was detectable in the roots, its content decreased when NH4(+) was supplied. Retrotransposon-mediated knockout mutants lacking AS1 showed slight stimulation of shoot length and slight reduction in root length at the seedling stage. On the other hand, the mutation caused an approximately 80-90% reduction in free asparagine content in both roots and xylem sap. These results suggest that AS1 is responsible for the synthesis of asparagine in rice roots following the supply of NH4(+). Characteristics of the NH4(+)-dependent increase and the root surface cell-specific expression of OsAS1 gene are very similar to our previous results on cytosolic glutamine synthetase1;2 and NADH-glutamate synthase1 in rice roots. Thus, AS1 is apparently coupled with the primary assimilation of NH4(+) in rice roots.

Risk factors for automobile accidents caused by falling asleep while driving in obstructive sleep apnea syndrome.

PURPOSE: We examined the risk factors for automobile accidents caused by falling asleep while driving in subjects with obstructive sleep apnea syndrome (OSAS). METHODS: We asked licensed drivers with history of snoring and excessive daytime sleepiness who had undergone polysomnography (PSG) at the Department of Sleep Medicine/Sleep Disorders Center at Aichi Medical University Hospital to complete the questionnaires on accidents caused by falling asleep while driving. As a subjective measure of sleepiness, we used the Epworth sleepiness scale (ESS). Based on PSG results, 2387 subjects diagnosed with OSAS were divided into three groups according to apnea-hypopnea index (AHI): mild-to-moderate (5 ≤ AHI < 30), severe (30 ≤ AHI < 60), and very severe (AHI ≥ 60). We performed univariate and multivariate logistic regression on variables that might explain falling asleep at the wheel. RESULTS: We compared results between each group and simple snorers (394 subjects with AHI < 5) and found the group with very severe OSAS reported significantly higher rates of driving when drowsy and having accidents in the past 5 years due to falling asleep. CONCLUSIONS: Our multivariate analysis suggests that scores on the ESS and patient-reported frequency of feeling drowsy while regular driving and working are related to automobile accidents caused by falling asleep while driving.

NADH-dependent glutamate synthase plays a crucial role in assimilating ammonium in the Arabidopsis root.

Plant roots under nitrogen deficient conditions with access to both ammonium and nitrate ions, will take up ammonium first. This preference for ammonium rather than nitrate emphasizes the importance of ammonium assimilation machinery in roots. Glutamine synthetase (GS) and glutamate synthase (GOGAT) catalyze the conversion of ammonium and 2-oxoglutarate to glutamine and glutamate. Higher plants have two GOGAT species, ferredoxin-dependent glutamate synthase (Fd-GOGAT) and nicotinamide adenine dinucleotide (NADH)-GOGAT. While Fd-GOGAT participates in the assimilation of ammonium, which is derived from photorespiration in leaves, NADH-GOGAT is highly expressed in roots and its importance needs to be elucidated. While ammonium as a minor nitrogen form in most soils is directly taken up, nitrate as the major nitrogen source needs to be converted to ammonium prior to uptake. The aim of this study was to investigate and quantify the contribution of NADH-GOGAT to the ammonium assimilation in Arabidopsis (Arabidopsis thaliana Columbia) roots. Quantitative real-time polymerase chain reaction (PCR) and protein gel blot analysis showed an accumulation of NADH-GOGAT in response to ammonium supplied to the roots. In addition the localization of NADH-GOGAT and Fd-GOGAT did not fully overlap. Promoter-ß-glucuronidase (GUS) fusion analysis and immunohistochemistry showed that NADH-GOGAT was highly accumulated in non-green tissue like vascular bundles, shoot apical meristem, pollen, stigma and roots. Reverse genetic approaches suggested a reduction in glutamate production and biomass accumulation in NADH-GOGAT transfer DNA (T-DNA) insertion lines under normal CO2 condition. The data emphasize the importance of NADH-GOGAT in the ammonium assimilation in Arabidopsis roots.

Risk factors for collisions attributed to microsleep-related behaviors while driving in professional truck drivers.

Sleep-disordered breathing (SDB) is prevalent among professional drivers. Although SDB is a known risk factor for truck collisions attributed to microsleep-related behaviors at the wheel (TC-MRBs), the usefulness of overnight pulse oximetry for predicting TC-MRBs is debatable. This retrospective study assessed the association between overnight pulse oximetry parameters, the Epworth Sleepiness Scale (ESS), and TC-MRBs, confirmed by dashcam footage. This study included 108 matched professional truck drivers (TC-MRBs: N = 54; non-TC-MRBs: N = 54), with a mean age and body mass index of 41.9 ± 11.3 years and 23.0 ± 3.7 kg/m2, respectively. Night-time drivers, 4% oxygen desaturation index (ODI), and nadir oxygen saturation (SpO2) were associated with TC-MRBs (odds ratio [95% confidence interval]: 25.63 [5.88-111.77], p < 0.0001; 2.74 [1.02-7.33], p = 0.045; and 3.87 [1.04-14.39], p = 0.04, respectively). The area under the curve of 4% ODI and nadir SpO2 for TC-MRBs were 0.50 and 0.57, respectively. In conclusion, night-time driving, 4% ODI, and nadir SpO2 were significantly associated with TC-MRBs in professional truck drivers. However, the sensitivity of overnight pulse oximetry parameters to predict TC-MRBs in a real-world application was poor. Therefore, combining subjective and objective assessments such as dashcam video footage may be needed to achieve high accuracy for predicting TC-MRBs among professional truck drivers.

Truck collisions attributed to falling asleep at the wheel in two commercial drivers prescribed oral appliance therapy for obstructive sleep apnea.

Falling asleep at the wheel is attributed to sleepiness, and obstructive sleep apnea is a significant cause of sleepiness that increases the risk of motor vehicle collisions due to falling asleep at the wheel. Although continuous positive airway pressure therapy for obstructive sleep apnea reduces the risk of motor vehicle collisions, similar evidence for alternatives such as oral appliance therapy is lacking. We discuss two truck collisions attributed to microsleep confirmed with dashcam video footage of commercial drivers with obstructive sleep apnea. Our results highlight the current situation where there is insufficient evidence for the prevention and reduction of the risk of motor vehicle collisions by oral appliance therapy, objective adherence monitoring of oral appliance therapy, and effectiveness confirmation tests. Therefore, it is suggested that for commercial truck drivers who require a high level of driving safety, careful selection for oral appliance therapy, systematic follow-up, and monitoring of the driver and truck status with dashcam video footage are crucial. CITATION: Kumagai H, Tsuda H, Kawaguchi K, et al. Truck collisions attributed to falling asleep at the wheel in two commercial drivers prescribed oral appliance therapy for obstructive sleep apnea. J Clin Sleep Med. 2023;19(12):2117-2122.

Effects of Continuous Positive Airway Pressure Therapy on Nocturnal Blood Pressure Fluctuation Patterns in Patients with Obstructive Sleep Apnea.

This retrospective study was designed to evaluate the effects of continuous positive airway pressure (CPAP) therapy, a well-established treatment for obstructive sleep apnea (OSA), on nocturnal blood pressure fluctuations (NBPFs) during rapid eye movement (REM) and non-REM sleep, and to evaluate the NBPF patterns in patients with OSA. We included 34 patients with moderate-to-severe OSA who underwent polysomnography using pulse transit time before and at 3−6 months after CPAP therapy. Nocturnal BP and NBPF frequency in REM and non-REM sleep were investigated, as well as NBPF pattern changes after receiving CPAP therapy. CPAP therapy resulted in significant reductions in the apnea−hypopnea index (AHI), arousal index, nocturnal systolic and diastolic BP, and NBPF frequency in REM and non-REM sleep (all p < 0.01). A higher AHI before CPAP resulted in lower nocturnal systolic BP (r = 0.40, p = 0.019) and NBPFs (r = 0.51, p = 0.002) after CPAP. However, 58.8% of patients showed no change in NBPF patterns with CPAP therapy. CPAP therapy significantly improved almost all sleep-related parameters, nocturnal BP, and NBPF frequency in REM and non-REM sleep periods, but NBPF patterns showed various changes post-CPAP therapy. These results suggest that factors other than OSA influence changes in NBPF patterns.

Nocturnal hypoxemia is related to morning negative affectivity in untreated patients with severe obstructive sleep apnea.

The relationship between sleep apnea and morning affectivity remains unclear. We aimed to clarify how sleep disturbance in patients with obstructive sleep apnea (OSA) influences their affectivity. The enrolled participants underwent the Positive and Negative Affect Schedule on their beds immediately before and after overnight polysomnography. Thirty patients with OSA were divided into two groups according to the apnea-hypopnea index (AHI): mild to moderate OSA (5 ≤ AHI < 30/h) and severe OSA (AHI ≥ 30/h) groups. Additionally, 11 healthy participants (AHI < 5/h) were included as the control group. No independent association was found between affectivity and OSA severity markers in the whole population; however, the severe OSA group had a significantly higher cumulative percentage of sleep time at saturations < 90% (CT90) and worsened morning negative affectivity. Multiple regression analysis showed that CT90 was an independent factor for increasing negative affectivity in the severe OSA group (p = 0.0422). In patients with OSA, the receiver operating characteristic curve analysis showed that the best cutoff value for CT90 for predicting no decrease in negative affectivity after sleep was 1.0% (sensitivity = 0.56, specificity = 0.86); the corresponding area under the curve was 0.71. Worsening of negative affectivity in the morning was influenced by nocturnal hypoxemia in patients with severe OSA.