Harnessing enzyme cofactors and plant metabolism: an essential partnership.

Cofactors are fundamental to the catalytic activity of enzymes. Additionally, because plants are a critical source of several cofactors (i.e., including their vitamin precursors) within the context of human nutrition, there have been several studies aiming to understand the metabolism of coenzymes and vitamins in plants in detail. For example, compelling evidence has been brought forth regarding the role of cofactors in plants; specifically, it is becoming increasingly clear that an adequate supply of cofactors in plants directly affects their development, metabolism, and stress responses. Here, we review the state-of-the-art knowledge on the significance of coenzymes and their precursors with regard to general plant physiology and discuss the emerging functions attributed to them. Furthermore, we discuss how our understanding of the complex relationship between cofactors and plant metabolism can be used for crop improvement.

Prospective Evaluation of Ease and Difficulties of 869 Cases of Intrauterine Devices Removals.

OBJECTIVES: The objective was to describe the ease and difficulty of removing intrauterine devices (IUDs). METHODS: We conducted a prospective study at the University of Campinas (UNICAMP), Faculty of Medical Sciences, UNICAMP. We included women who requested IUD removal. We excluded women with partial IUD expulsion in which the IUD was protruded at the external os. We identified difficult IUD removal when the removal was challenging, including the inability to visualize IUD strings extending from the cervical os. RESULTS: A total of 869 women participated. Women were aged 29.4 ± 8.0 years (mean ± SD; range 14-51) and the duration of IUD use at the time of removal was 4.3 ± 4.2 years. We found that 702 (80.8%) women had visible strings at the external os and the removals were performed at the first attempt without difficulty in 692 (79.6%) participants. The pain was more intense (>4) in cases of difficult removals. After multivariate logistic analysis, difficult removals were associated with users of IUD ≥3 years (3 times higher risk); for each previous cesarean delivery, the risk increased by 1.5 times. CONCLUSIONS: Our study showed that IUD removal is an easy and safe procedure, with only a small proportion of women reporting significant pain with IUD removal.

Using interoperable nursing care data to improve outcomes for multiple traumas patients with Impaired Physical Mobility.

AIM(S): To demonstrate how interoperable nursing care data can be used by nurses to create a more holistic understanding of the healthcare needs of multiple traumas patients with Impaired Physical Mobility. By proposing and validating linkages for the nursing diagnosis of Impaired Physical Mobility in multiple trauma patients by mapping to the Nursing Outcomes Classification (NOC) and Nursing Interventions Classification (NIC) equivalent terms using free-text nursing documentation. DESIGN: A descriptive cross-sectional design, combining quantitative analysis of interoperable data sets and the Kappa's coefficient score with qualitative insights from cross-mapping methodology and nursing professionals' consensus. METHODS: Cross-mapping methodology was conducted in a Brazilian Level 1 Trauma Center using de-identified records of adult patients with a confirmed medical diagnosis of multiple traumas and Impaired Physical Mobility (a nursing diagnosis). The hospital nursing free-text records were mapped to NANDA-I, NIC, NOC and NNN linkages were identified. The data records were retrieved for admissions from September to October 2020 and involved medical and nursing records. Three expert nurses evaluated the cross-mapping and linkage results using a 4-point Likert-type scale and Kappa's coefficient. RESULTS: The de-identified records of 44 patients were evaluated and then were mapped to three NOCs related to nurses care planning: (0001) Endurance; (0204) Immobility Consequences: Physiological, and (0208) Mobility and 13 interventions and 32 interrelated activities: (6486) Environmental Management: Safety; (0840) Positioning; (3200) Aspiration Precautions; (1400) Pain Management; (0940) Traction/Immobilization Care; (3540) Pressure Ulcer Prevention; (3584) Skincare: Topical Treatment; (1100) Nutrition Management; (3660) Wound Care; (1804) Self-Care Assistance: Toileting; (1801) Self-Care Assistance: Bathing/Hygiene; (4130) Fluid Monitoring; and (4200) Intravenous Therapy. The final version of the constructed NNN Linkages identified 37 NOCs and 41 NICs. CONCLUSION: These valid NNN linkages for patients with multiple traumas can serve as a valuable resource that enables nurses, who face multiple time constraints, to make informed decisions efficiently. This approach of using evidence-based linkages like the one developed in this research holds high potential for improving patient's safety and outcomes. NO PATIENT OR PUBLIC CONTRIBUTION: In this study, there was no direct involvement of patients, service users, caregivers or public members in the design, conduct, analysis and interpretation of data or preparation of the manuscript. The study focused solely on analysing existing de-identified medical and nursing records to propose and validate linkages for nursing diagnoses.

Improvement of laboratory markers of anaemia in the treatment of heavy menstrual bleeding with a 19.5-mg intrauterine device: a pilot study.

OBJECTIVES: To evaluate improvements in laboratory markers of anaemia (haemoglobin, haematocrit, serum iron, and ferritin) in women with subjective heavy menstrual bleeding (HMB) treated with the levonorgestrel 19.5-mg intrauterine device. MATERIALS AND METHODS: We conducted a pilot study at the Department of Obstetrics and Gynaecology, University of Campinas, Faculty of Medical Sciences, Campinas, SP, Brazil. We compared anaemia markers in 73 women aged 18-48 years suffering from HMB, one year after placement of the IUD. RESULTS: The mean age of participants was 30.0 years (range 24-38); more than half were white, and the mean body mass index (kg/m2) was 27.0. Twenty (27.4%) participants exited the study due to loss to follow-up (n = 12; 16.4%), expulsion (n = 7; 9.6%) and uterine perforation (n = 1; 1.4%). One-year post-IUD placement, amenorrhoea was reported by 10 (13.7%) women. According to intention-to-treat and per protocol analyses, the proportion of women with normal haemoglobin levels significantly improved (p = 0.014 in both analyses), as did haematocrit (p < 0.001 in both analyses) and serum iron (p = 0.003 in both analyses) compared to baseline evaluations. The proportion of women with normal ferritin levels also improved (p < 0.001) in both analyses using a cut-off of 15 ng/ml, though no significant difference was observed using a 30 ng/ml cut-off (p = 0.083 in both analyses). CONCLUSION: The levonorgestrel 19.5-mg IUD effectively improved laboratory markers of anaemia one year after placement in women with HMB.

Our results show that the levonorgestrel 19.5-mg IUD significantly improved anaemia markers in subjects with subjective HMB one year after insertion. The occurrence of expulsions emerged as a notable concern in this treatment group.

Pain relief during intrauterine device placement in nulligravid women with both oral ketorolac and an analgesic: a double-blinded randomised trial.

OBJECTIVE: We assessed whether the administration of oral ketorolac with an analgesic provides effective pain relief during placement of an intrauterine device (IUD) in nulligravid women. METHODS: We conducted a double-blinded randomised trial in the Department of Obstetrics and Gynaecology, University of Campinas Faculty of Medical Sciences, Campinas, SP, Brazil. We randomised participants who voluntarily agreed to participate to receive either one pill containing ketorolac 20 mg together with one pill containing dipyrone 300 mg, scopolamine 6.5 µg, hyoscyamine 104 µg, and homatropine 1 mg or placebo 60 min before IUD placement. The participants and providers were blinded to the randomisation group. The primary outcome was pain assessment (measured on a 0-10 visual analogue scale) during IUD placement. RESULTS: We enrolled participants and randomised them 1:1 between November 7, 2023, and January 31, 2024. We analysed 60 women in each group. There were no differences between the groups in the pain score during tenaculum placement, uterine sounding, and IUD placement, and in the overall perception of pain. However, the pain score was significantly lower 10 min after the procedure in women who received the treatment compared with women who received the placebo. CONCLUSION: Oral ketorolac associated with an analgesic administered 60 min before IUD placement was not significantly better than placebo during tenaculum placement, uterine sounding, and IUD insertion, and did not significantly reduce the overall pain perception. However, this treatment did significantly reduce pain 10 min after the procedure. TRIAL REGISTRATION: The trial was registered at Registro Brasileiro de Ensaios Clínicos (REBEC; in English: The Brazilian Registry of Clinical Trials) under number RBR-7phn8yv on November 6, 2023. https://ensaiosclinicos.gov.br/rg/RBR-7phn8yv.

Pain at IUD placement after one pill containing ketorolac 20 mg together with one analgesic pill given 60 min before placement were similar than placebo.

The Arabidopsis electron-transfer flavoprotein:ubiquinone oxidoreductase is required during normal seed development and germination.

The importance of the alternative donation of electrons to the ubiquinol pool via the electron-transfer flavoprotein/electron-transfer flavoprotein:ubiquinone oxidoreductase (ETF/ETFQO) complex has been demonstrated. However, the functional significance of this pathway during seed development and germination remains to be elucidated. To assess the function of this pathway, we performed a detailed metabolic and transcriptomic analysis of Arabidopsis mutants to test the molecular consequences of a dysfunctional ETF/ETFQO pathway. We demonstrate that the disruption of this pathway compromises seed germination in the absence of an external carbon source and also impacts seed size and yield. Total protein and storage protein content is reduced in dry seeds, whilst sucrose levels remain invariant. Seeds of ETFQO and related mutants were also characterized by an altered fatty acid composition. During seed development, lower levels of fatty acids and proteins accumulated in the etfqo-1 mutant as well as in mutants in the alternative electron donors isovaleryl-CoA dehydrogenase (ivdh-1) and d-2-hydroxyglutarate dehydrogenase (d2hgdh1-2). Furthermore, the content of several amino acids was increased in etfqo-1 mutants during seed development, indicating that these mutants are not using such amino acids as alternative energy source for respiration. Transcriptome analysis revealed alterations in the expression levels of several genes involved in energy and hormonal metabolism. Our findings demonstrated that the alternative pathway of respiration mediated by the ETF/ETFQO complex affects seed germination and development by directly adjusting carbon storage during seed filling. These results indicate a role for the pathway in the normal plant life cycle to complement its previously defined roles in the response to abiotic stress.

Mitochondrial and peroxisomal NAD+ uptake are important for improved photosynthesis and seed yield under elevated CO2 concentrations.

As sessile organisms, plants must adapt their physiology and developmental processes to cope with challenging environmental circumstances, such as the ongoing elevation in atmospheric carbon dioxide (CO2 ) levels. Nicotinamide adenine dinucleotide (NAD+ ) is a cornerstone of plant metabolism and plays an essential role in redox homeostasis. Given that plants impaired in NAD metabolism and transport often display growth defects, low seed production and disturbed stomatal development/movement, we hypothesized that subcellular NAD distribution could be a candidate for plants to exploit the effects of CO2 fertilization. We report that an efficient subcellular NAD+ distribution is required for the fecundity-promoting effects of elevated CO2 levels. Plants with reduced expression of either mitochondrial (NDT1 or NDT2) or peroxisomal (PXN) NAD+ transporter genes grown under elevated CO2 exhibited reduced total leaf area compared with the wild-type while PXN mutants also displayed reduced leaf number. NDT2 and PXN lines grown under elevated CO2 conditions displayed reduced rosette dry weight and lower photosynthetic rates coupled with reduced stomatal conductance. Interestingly, high CO2 doubled seed production and seed weight in the wild-type, whereas the mutants were less responsive to increases in CO2 levels during reproduction, producing far fewer seeds than the wild-type under both CO2 conditions. These data highlight the importance of mitochondrial and peroxisomal NAD+ uptake mediated by distinct NAD transporter proteins to modulate photosynthesis and seed production under high CO2 levels.

Aerosol optical properties over the South Atlantic and southern ocean during the 2010-2012 summer seasons as part of the global maritime aerosol network.

Aerosols have implications to climate and biogeochemical cycles in the global oceans. At sites under indirect influence of dust emitted by the Patagonian semi-desert, a debate exists on the potential fertilization effects of iron enriched aerossol. Considering this subject we conducted measurements of aerosols optical properties using a Microtops II sun photometer to access aerosol size distributions and other intrinsic properties oversea from Atlantic Southern mid-latitudes to Antarctica. Oceanographic cruises were developed between December 2010 to April 2011 and October 2011 to April 2012, in the context of the Brazilian Antarctic Program, and between November 2011 to December 2011. This survey was taken as part of the Global Maritime Aerosol Network (MAN/NASA). Our data of AOD (500 nm) along the South American coast depicts a steady decrease southwards following the decreased latitudinal continental extent. However, the influence of the aerosols blown from Patagonia semi-desert region was clear from latitude 53°S to 64°S. The predominance of aerosol fine mode was observed in Central Atlantic and close to the Drake Passage. An unexpected aerosol coarse mode predominance was found close to the Antarctic Peninsula. We attribute that to a possible weathering of rock outcrops due to the strong westerly winds in that region.

Does Fetal Growth Adequacy Affect the Nutritional Composition of Mothers' Milk?: A Historical Cohort Study.

OBJECTIVE: The study aimed to assess the association between intrauterine growth of preterm infants and energy and macronutrient contents in their mothers' milk. STUDY DESIGN: A historical cohort of mothers of preterm infants was assessed according to offspring's intrauterine growth. Fetal growth restriction (FGR) was defined as small-for-gestational age or appropriate for gestational age with fetal growth deceleration. During the first 4 weeks after delivery, the composition of daily pool samples of mothers' milk was measured by using a mid-infrared human milk analyzer. Explanatory models for milk energy, true protein, total carbohydrate, and fat contents were obtained by generalized additive mixed effects regression models. RESULTS: In total, 127 milk samples were analyzed from 73 mothers who delivered 92 neonates. Energy content was significantly higher in mothers with chronic hypertension (average: +6.28 kcal/dL; 95% confidence interval [CI]: 0.54-12.01; p = 0.034) and for extremely preterm compared with very preterm infants (average: +5.95 kcal/dL; 95% CI: 2.16-9.73; p = 0.003), and weakly associated with single pregnancies (average: +3.38 kcal/dL; 95% CI: 0.07-6.83; p = 0.057). True protein content was significantly higher in mothers with chronic hypertension (average: +0.91 g/dL; 95% CI: 0.63-1.19; p < 0.001) and with hypertension induced by pregnancy (average: +0.25 g/dL, 95% CI: 0.07-0.44; p = 0.007), and for extremely preterm compared with very and moderate preterm infants (average: +0.19; 95% CI: 0.01-0.38; p = 0.043 and +0.28 g/dL; 95% CI: 0.05-0.51; p = 0.017, respectively). Fat content was weakly and negatively associated with FGR, both in SGA infants and AGA infants with fetal growth deceleration (average: -0.44 g/dL; 95% CI: -0.92 to -0.05; p = 0.079 and average: -0.36 g/dL; 95% CI: -0.74 to -0.02; p = 0.066, respectively). CONCLUSION: Energy and macronutrient contents in mothers' milk of preterm infants was significantly and positively associated with the degree of prematurity and hypertension. The hypothesis that the composition of milk is associated with FGR was not demonstrated. KEY POINTS: · Energy and protein are higher for more immature infants.. · Energy and/or protein is higher in hypertension.. · Fat may be lower for infants with intrauterine growth restriction..

Disclosing the Biocide Activity of α-Ag2-2xCuxWO4 (0 ≤ x ≤ 0.16) Solid Solutions.

In this work, α-Ag2-2xCuxWO4 (0 ≤ x ≤ 0.16) solid solutions with enhanced antibacterial (against methicillin-resistant Staphylococcus aureus) and antifungal (against Candida albicans) activities are reported. A plethora of techniques (X-ray diffraction with Rietveld refinements, inductively coupled plasma atomic emission spectrometry, micro-Raman spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy, field emission scanning electron microscopy, ultraviolet-visible spectroscopy, photoluminescence emissions, and X-ray photoelectron spectroscopy) were employed to characterize the as-synthetized samples and determine the local coordination geometry of Cu2+ cations at the orthorhombic lattice. To find a correlation between morphology and biocide activity, the experimental results were sustained by first-principles calculations at the density functional theory level to decipher the cluster coordinations and electronic properties of the exposed surfaces. Based on the analysis of the under-coordinated Ag and Cu clusters at the (010) and (101) exposed surfaces, we propose a mechanism to explain the biocide activity of these solid solutions.

Natural contraception apps knowledge among Brazilian women and Obstetrics and Gynaecology residents.

BACKGROUND: Our objectives were to determine the knowledge and interest in apps for natural contraception among women and Obstetrics and Gynaecology (OBGYN) residents. STUDY DESIGN: An online survey was sent to Brazilian women to gather sociodemographic data, knowledge and interest towards fertility-awareness contraceptive methods and smartphone apps for this purpose. Also, we sent an online survey to OBGYN residents to evaluate the reproductive physiology knowledge of natural contraception and interest in improving it and knowledge and smartphone apps for this purpose. RESULTS: A total of 730 women answered the survey, and 638 were included in the study and 94 OBGYN residents answered the survey. Among the respondent women 386 (60.5%) were interested in more information about natural contraception, 226 (35.5%) showed interest in use natural contraception, 85 (13.3%) indicated that they were users of natural contraception, 15 (16.8%) of this group currently uses an app for this purpose and 485 (76%) considers a practical option to have an app for natural contraception. Regarding the respondent residents all answers were included in the study; 62 (65.9%) knew the right definition of 'Natural Contraception', 52 (55.3%) showed interest in information about this topic and 78 (82.9%) considers a practical option to have an app for natural contraception. CONCLUSIONS: Less than 15% of the respondent women use natural contraception although about 60% expressed some interest in learning more, and that among OBGYN residents, half showed interest.

Changes in intracellular NAD status affect stomatal development in an abscisic acid-dependent manner.

Nicotinamide adenine dinucleotide (NAD) plays a central role in redox metabolism in all domains of life. Additional roles in regulating posttranslational protein modifications and cell signaling implicate NAD as a potential integrator of central metabolism and programs regulating stress responses and development. Here we found that NAD negatively impacts stomatal development in cotyledons of Arabidopsis thaliana. Plants with reduced capacity for NAD+ transport from the cytosol into the mitochondria or the peroxisomes exhibited reduced numbers of stomatal lineage cells and reduced stomatal density. Cotyledons of plants with reduced NAD+ breakdown capacity and NAD+ -treated cotyledons also presented reduced stomatal number. Expression of stomatal lineage-related genes was repressed in plants with reduced expression of NAD+ transporters as well as in plants treated with NAD+ . Impaired NAD+ transport was further associated with an induction of abscisic acid (ABA)-responsive genes. Inhibition of ABA synthesis rescued the stomatal phenotype in mutants deficient in intracellular NAD+ transport, whereas exogenous NAD+ feeding of aba-2 and ost1 seedlings, impaired in ABA synthesis and ABA signaling, respectively, did not impact stomatal number, placing NAD upstream of ABA. Additionally, in vivo measurement of ABA dynamics in seedlings of an ABA-specific optogenetic reporter - ABAleon2.1 - treated with NAD+ showed increases in ABA content suggesting that NAD+ impacts on stomatal development through ABA synthesis and signaling. Our results demonstrate that intracellular NAD+ homeostasis as set by synthesis, breakdown and transport is essential for normal stomatal development, and provide a link between central metabolism, hormone signaling and developmental plasticity.

Thioredoxin-mediated regulation of (photo)respiration and central metabolism.

Thioredoxins (TRXs) are ubiquitous proteins engaged in the redox regulation of plant metabolism. Whilst the light-dependent TRX-mediated activation of Calvin-Benson cycle enzymes is well documented, the role of extraplastidial TRXs in the control of the mitochondrial (photo)respiratory metabolism has been revealed relatively recently. Mitochondrially located TRX o1 has been identified as a regulator of alternative oxidase, enzymes of, or associated with, the tricarboxylic acid (TCA) cycle, and the mitochondrial dihydrolipoamide dehydrogenase (mtLPD) involved in photorespiration, the TCA cycle, and the degradation of branched chain amino acids. TRXs are seemingly a major point of metabolic regulation responsible for activating photosynthesis and adjusting mitochondrial photorespiratory metabolism according to the prevailing cellular redox status. Furthermore, TRX-mediated (de)activation of TCA cycle enzymes contributes to explain the non-cyclic flux mode of operation of this cycle in illuminated leaves. Here we provide an overview on the decisive role of TRXs in the coordination of mitochondrial metabolism in the light and provide in silico evidence for other redox-regulated photorespiratory enzymes. We further discuss the consequences of mtLPD regulation beyond photorespiration and provide outstanding questions that should be addressed in future studies to improve our understanding of the role of TRXs in the regulation of central metabolism.

Structure, Photoluminescence Emissions, and Photocatalytic Activity of Ag2SeO3: A Joint Experimental and Theoretical Investigation.

In this paper, we report the synthesis of silver selenite (Ag2SeO3) by different methods [sonochemistry, ultrasonic probe, coprecipitation, and microwave-assisted hydrothermal methods]. These microcrystals presented a structural long-range order as confirmed by X-ray diffraction (XRD) and Rietveld refinements and a structural short-range order as confirmed by Fourier transform infrared (FTIR) and Raman spectroscopies. X-ray photoelectron spectroscopy (XPS) provided information about the surface of the samples indicating that they were pure. The microcrystals presented different morphologies and sizes due to the synthesis method as observed by field emission scanning electron microscopy (FE-SEM). The optical properties of these microcrystals were evaluated by ultraviolet-visible (UV-vis) spectroscopy and photoluminescence (PL) measurements. Thermal analysis confirmed the temperature stability of the as-synthetized samples. Further trapping experiments prove that the holes and hydroxyl radicals, to a minor extent, are responsible for the photocatalytic reactions. The experimental results are sustained by first-principles calculations, at the density functional theory (DFT) level, to decipher the structural parameters, electronic properties of the bulk, and surfaces of Ag2SeO3. By matching the experimental FE-SEM images and theoretical morphologies, we are capable of finding a correlation between the morphology and photocatalytic activity, along with photodegradation of the Rhodamine B dye under UV light, based on the different numbers of unsaturated superficial Ag and Se cations (local coordination, i.e., clusters) of each surface.

The use of guarana (Paullinia cupana) as a dietary supplement for fatigue in cancer patients: a systematic review with a meta-analysis.

OBJECTIVE: The objective of the present study was to carry out a systematic review with a meta-analysis to assess evidence about the use of guarana fruit to manage fatigue in cancer patients. METHODOLOGY: The data were extracted from the EMBASE, Scopus, MEDLINE, CENTRAL, and CINAHL databases, in any language, using the descriptors "neoplasms" and "Paullinia" or "guarana powder" and "placebos" and "fatigue". Searches were also conducted to identify any grey literature. Clinical studies with patients who presented cancer-related fatigue as a primary outcome and who used guarana as a dietary supplement were included. The risk of bias in randomized clinical trials was analyzed according to the Cochrane recommendations. The quality of the evidence was assessed using the GRADE system. For studies with the same types of tumors and treatments, meta-analysis was also conducted. RESULTS: A total of 383 studies were found and, of these, seven were included in the review, for a total of 427 cancer patients. The instruments used to analyze fatigue were the Brief Fatigue Inventory (BFI), the Chalder Fatigue Scale, the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-FATIGUE), and the Piper Scale. Some studies presented a low risk of bias for all the categories. Meta-analysis was conducted for three studies about breast cancer, which presented sufficient data. The use of guarana did not reduce cancer-related fatigue compared with placebo groups (mean of - 0.02 [95% CI - 1.54, 1.50]; p = 0.98) and the quality of evidence according to GRADE was very low. CONCLUSION: Dietary supplements are used to improve cancer-related fatigue. The results of this review showed that the use of guarana was not superior to the placebo groups, pointing to the need for further studies with better methodological quality.

Opuntia ficus-indica (L.) Mill.: A Multi-Benefit Potential to Be Exploited.

Consumer interest in foods with enhanced nutritional quality has increased in recent years. The nutritional and bioactive characterization of fruits and their byproducts, as well as their use in the formulation of new food products, is advisable, contributing to decrease the global concerns related to food waste and food security. Moreover, the compounds present in these raw materials and the study of their biological properties can promote health and help to prevent some chronic diseases. Opuntia ficus-indica (L.) Mill. (prickly pear) is a plant that grows wild in the arid and semi-arid regions of the world, being a food source for ones and a potential for others, but not properly valued. This paper carries out an exhaustive review of the scientific literature on the nutritional composition and bioactive compounds of prickly pear and its constituents, as well as its main biological activities and applications. It is a good source of dietary fiber, vitamins and bioactive compounds. Many of its natural compounds have interesting biological activities such as anti-inflammatory, hypoglycemic and antimicrobial. The antioxidant power of prickly pear makes it a good candidate as an ingredient of new food products with fascinating properties for health promotion and/or to be used as natural extracts for food, pharmaceutic or cosmetic applications. In addition, it could be a key player in food security in many arid and semi-arid regions of the world, where there are often no more plants.

Upper airways after mandibular advancement orthognathic surgery: A 4-year follow-up.

INTRODUCTION: The purpose of this study was to assess the stability of changes in the upper airways 4 years after orthognathic surgery in patients with skeletal Class II malocclusion. METHODS: A retrospective clinical study was conducted including 33 cone-beam computed tomography images from 11 patients (average age of 35.91 years) followed up longitudinally for 4 years. The airways were measured with the help of the Dolphin Imaging software (Dolphin Imaging and Management Systems, Chatsworth, Calif) at 3 points: T1 (preoperative), T2 (6 months after surgery), and T3 (4 years after surgery). The parameters assessed were surface area (SA), minimum axial area, and volume (VOL) of the pharyngeal airway space. The times were compared using analysis of variance and Tukey's test. Pearson's analysis was performed to assess the correlation with surgical changes and age (P <0.05). RESULTS: Four years after operating on the airway spaces, the means of SA and VOL were significantly higher than those observed before the surgery (P <0.05). The means at 6 months were intermediate, with no significant difference before the surgery and 4 years after it (P >0.05). There was no significant correlation of the changes in SA, VOL, and minimum axial area with the amount of mandibular advancement, counterclockwise rotation of the occlusal plane, and age of the patient (P >0.05). CONCLUSIONS: Four years after mandibular advancement surgery in patients with skeletal Class II malocclusion, the increases in the airways remained stable.

The mitochondrial NAD+ transporter (NDT1) plays important roles in cellular NAD+ homeostasis in Arabidopsis thaliana.

Nicotinamide adenine dinucleotide (NAD+ ) is an essential coenzyme required for all living organisms. In eukaryotic cells, the final step of NAD+ biosynthesis is exclusively cytosolic. Hence, NAD+ must be imported into organelles to support their metabolic functions. Three NAD+ transporters belonging to the mitochondrial carrier family (MCF) have been biochemically characterized in plants. AtNDT1 (At2g47490), focus of the current study, AtNDT2 (At1g25380), targeted to the inner mitochondrial membrane, and AtPXN (At2g39970), located in the peroxisomal membrane. Although AtNDT1 was presumed to reside in the chloroplast membrane, subcellular localization experiments with green fluorescent protein (GFP) fusions revealed that AtNDT1 locates exclusively in the mitochondrial membrane in stably transformed Arabidopsis plants. To understand the biological function of AtNDT1 in Arabidopsis, three transgenic lines containing an antisense construct of AtNDT1 under the control of the 35S promoter alongside a T-DNA insertional line were evaluated. Plants with reduced AtNDT1 expression displayed lower pollen viability, silique length, and higher rate of seed abortion. Furthermore, these plants also exhibited an increased leaf number and leaf area concomitant with higher photosynthetic rates and higher levels of sucrose and starch. Therefore, lower expression of AtNDT1 was associated with enhanced vegetative growth but severe impairment of the reproductive stage. These results are discussed in the context of the mitochondrial localization of AtNDT1 and its important role in the cellular NAD+ homeostasis for both metabolic and developmental processes in plants.

Downregulation of a Mitochondrial NAD+ Transporter (NDT2) Alters Seed Production and Germination in Arabidopsis.

Despite the fundamental importance of nicotinamide adenine dinucleotide (NAD+) for metabolism, the physiological roles of NAD+ carriers in plants remain unclear. We previously characterized the Arabidopsis thaliana gene (At1g25380), named AtNDT2, encoding a protein located in the mitochondrial inner membrane, which imports NAD+ from the cytosol using ADP and AMP as counter-exchange substrates for NAD+. Here, we further investigated the physiological roles of NDT2, by isolating a T-DNA insertion line, generating an antisense line and characterizing these genotypes in detail. Reduced NDT2 expression affected reproductive phase by reducing total seed yield. In addition, reduced seed germination and retardation in seedling establishment were observed in the mutant lines. Moreover, remarkable changes in primary metabolism were observed in dry and germinated seeds and an increase in fatty acid levels was verified during seedling establishment. Furthermore, flowers and seedlings of NDT2 mutants displayed upregulation of de novo and salvage pathway genes encoding NAD+ biosynthesis enzymes, demonstrating the transcriptional control mediated by NDT2 activity over these genes. Taken together, our results suggest that NDT2 expression is fundamental for maintaining NAD+ balance amongst organelles that modulate metabolism, physiology and developmental processes of heterotrophic tissues.

Thioredoxin h2 contributes to the redox regulation of mitochondrial photorespiratory metabolism.

Thioredoxins (TRXs) are important proteins involved in redox regulation of metabolism. In plants, it has been shown that the mitochondrial metabolism is regulated by the mitochondrial TRX system. However, the functional significance of TRX h2, which is found at both cytosol and mitochondria, remains unclear. Arabidopsis plants lacking TRX h2 showed delayed seed germination and reduced respiration alongside impaired stomatal and mesophyll conductance, without impacting photosynthesis under ambient O2 conditions. However, an increase in the stoichiometry of photorespiratory CO2 release was found during O2 -dependent gas exchange measurements in trxh2 mutants. Metabolite profiling of trxh2 leaves revealed alterations in key metabolites of photorespiration and in several metabolites involved in respiration and amino acid metabolism. Decreased abundance of serine hydroxymethyltransferase and glycine decarboxylase (GDC) H and L subunits as well as reduced NADH/NAD+ ratios were also observed in trxh2 mutants. We further demonstrated that the redox status of GDC-L is altered in trxh2 mutants in vivo and that recombinant TRX h2 can deactivate GDC-L in vitro, indicating that this protein is redox regulated by the TRX system. Collectively, our results demonstrate that TRX h2 plays an important role in the redox regulation of mitochondrial photorespiratory metabolism.