Genetic mapping and prediction for novel lesion mimic in maize demonstrates quantitative effects from genetic background, environment and epistasis.

KEY MESSAGE: A novel locus was discovered on chromosome 7 associated with a lesion mimic in maize; this lesion mimic had a quantitative and heritable phenotype and was predicted better via subset genomic markers than whole genome markers across diverse environments. Lesion mimics are a phenotype of leaf micro-spotting in maize (Zea mays L.), which can be early signs of biotic or abiotic stresses. Dissecting its inheritance is helpful to understand how these loci behave across different genetic backgrounds. Here, 538 maize recombinant inbred lines (RILs) segregating for a novel lesion mimic were quantitatively phenotyped in Georgia, Texas, and Wisconsin. These RILs were derived from three bi-parental crosses using a tropical pollinator (Tx773) as the common parent crossed with three inbreds (LH195, LH82, and PB80). While this lesion mimic was heritable across three environments based on phenotypic ([Formula: see text] = 0.68) and genomic ([Formula: see text] = 0.91) data, transgressive segregation was observed. A genome-wide association study identified a single novel locus on chromosome 7 (at 70.6 Mb) also covered by a quantitative trait locus interval (69.3-71.0 Mb), explaining 11-15% of the variation, depending on the environment. One candidate gene identified in this region, Zm00001eb308070, is related to the abscisic acid pathway involving in cell death. Genomic predictions were applied to genome-wide markers (39,611 markers) contrasted with a marker subset (51 markers). Population structure explained more variation than environment in genomic prediction, but other substantial genetic background effects were additionally detected. Subset markers explained substantially less genetic variation (24.9%) for the lesion mimic than whole genome markers (55.4%) in the model, yet predicted the lesion mimic better (0.56-0.66 vs. 0.26-0.29). These results indicate this lesion mimic phenotype was less affected by environment than by epistasis and genetic background effects, which explain its transgressive segregation.

Investigation of Camera-Free Eye-Tracking Glasses Compared to a Video-Based System.

Technological advances in eye-tracking have resulted in lightweight, portable solutions that are capable of capturing eye movements beyond laboratory settings. Eye-tracking devices have typically relied on heavier, video-based systems to detect pupil and corneal reflections. Advances in mobile eye-tracking technology could facilitate research and its application in ecological settings; more traditional laboratory research methods are able to be modified and transferred to real-world scenarios. One recent technology, the AdHawk MindLink, introduced a novel camera-free system embedded in typical eyeglass frames. This paper evaluates the AdHawk MindLink by comparing the eye-tracking recordings with a research "gold standard", the EyeLink II. By concurrently capturing data from both eyes, we compare the capability of each eye tracker to quantify metrics from fixation, saccade, and smooth pursuit tasks-typical elements in eye movement research-across a sample of 13 adults. The MindLink system was capable of capturing fixation stability within a radius of less than 0.5∘, estimating horizontal saccade amplitudes with an accuracy of 0.04∘± 2.3∘, vertical saccade amplitudes with an accuracy of 0.32∘± 2.3∘, and smooth pursuit speeds with an accuracy of 0.5 to 3∘s, depending on the pursuit speed. While the performance of the MindLink system in measuring fixation stability, saccade amplitude, and smooth pursuit eye movements were slightly inferior to the video-based system, MindLink provides sufficient gaze-tracking capabilities for dynamic settings and experiments.

Insecticidal features displayed by the beneficial rhizobacterium Pseudomonas chlororaphis PCL1606.

The biocontrol rhizobacterium Pseudomonas chlororaphis is one of the bacterial species of the P. fluorescens group where insecticide fit genes have been found. Fit toxin, supported with other antimicrobial compounds, gives the bacterial the ability to repel and to fight against eukaryotic organisms, such as nematodes and insect larvae, thus protecting the plant host and itself. Pseudomonas chlororaphis PCL1606 is an antagonistic rhizobacterium isolated from avocado roots and show efficient biocontrol against fungal soil-borne disease. The main antimicrobial compound produced by P. chlororaphis PCL606 is 2-hexyl-5-propyl resorcinol (HPR), which plays a crucial role in effective biocontrol against fungal pathogens. Further analysis of the P. chlororaphis PCL1606 genome showed the presence of hydrogen cyanide (HCN), pyrrolnitrin (PRN), and homologous fit genes. To test the insecticidal activity and to determine the bases for such activity, single and double mutants on the biosynthetic genes of these four compounds were tested in a Galleria mellonella larval model using inoculation by injection. The results revealed that Fit toxin and HPR in combination are involved in the insecticide phenotype of P. chlororaphis PCL1606, and additional compounds such as HCN and PRN could be considered supporting compounds.

Do Patients Regret Having Received Systemic Treatment for Advanced Non-Small Cell Lung Cancer: A Prospective Evaluation.

BACKGROUND: Thousands of patients annually receive treatment for advanced non-small cell lung cancer (NSCLC), but little is known about their views on the decision to receive that treatment, or regret. This trial prospectively evaluated the incidence of regret and whether baseline characteristics, patient decision-making parameters, or clinical progress early in the treatment course predicts regret. MATERIALS AND METHODS: Patients receiving systemic treatment for advanced NSCLC completed every 3-week patient reported outcome (PRO) assessment using the electronic Lung Cancer Symptom Scale (eLCSS-QL), including the 3-Item Global Index (3-IGI; assessing overall distress, activities, and quality of life [QL]). A prespecified secondary aim was to determine the frequency of regret evaluated at 3 months after starting treatment. Patients were randomized to usual care or enhanced care (which included use of the DecisionKEYS decision aid). RESULTS: Of 164 patients entered, 160 received treatment and 142 were evaluable for regret. In total, 11.5% of patients and 9% of their supporters expressed regret. Baseline characteristics did not predict regret; regret was rarely expressed by those who had a less than 20% decline or improvement in the 3-IGI PRO score after two treatment cycles. In contrast, when asked if they would make the same decision again, only 1% not having a 20% 3-IGI decline expressed regret, versus 14% with a 3-IGI decline (p = .01). CONCLUSION: The majority of patients having regret were identified early using the PRO 3-IGI of the eLCSS-QL measure. Identifying patients at risk for regret allows for interventions, including frank discussions of progress and goals early in the treatment course, which could address regret in patients and their supporters. IMPLICATIONS FOR PRACTICE: This report documents prospectively, for the first time, the incidence of treatment-related regret in patients with advanced lung cancer and outlines that risk of regret is associated with patient-determined worsening health status early in the course of treatment. Identifying patients at risk for regret early in treatment (before the third cycle of treatment) appears to be crucial. Counseling at that time should include a discussion of consideration of treatment change and the reason for this change.

Longitudinal assessment of SARS-CoV-2 IgG seroconversionamong front-line healthcare workers during the first wave of the Covid-19 pandemic at a tertiary-care hospital in Chile.

BACKGROUND: Healthcare workers (HCWs) are at high risk of exposure to SARS-CoV-2. Cross-sectional studies have provided variable rates of seroprevalence in HCWs. Longitudinal assessments of the serological response to Covid-19 among HCWs are crucial to understanding the risk of infection and changes in antibody titers over time. We aimed to investigate seroprevalence and risk factors associated with seroconversion in a prospective cohort of HCWs during the peak of the first wave of the Covid-19 pandemic. METHODS: We conducted a longitudinal study among 446 front-line HCWsin a tertiary-care hospital in Chile from April to July 2020. IgG was determined monthly using two different ELISAs in serum samples of HCWs, during the three-month period. In each visit, demographic data, symptoms, risk factors, and exposure risks were also assessed. RESULTS: The overall seroprevalence at the end of the study period was 24% (95% CI20.2-28.3), with 43% of seropositive HCWs reporting no prior symptoms. Seroconversion rates significantly differed over the study period, from 2.1% to as high as 8.8% at the peak of the epidemic. There were no statistically significant differences observed between HCWs in direct clinical care of patients with Covid-19 and those working in low risk areas. Antibody titers appeared to wane over time. CONCLUSIONS: HCWs were severely affected with a high rate of seroconversion that appeared to mirror the local epidemiological situation. A significant amount of participants underwent an asymptomatic infection, highlighting the need for improved surveillance policies. Antibody titers appear to wane over time; further studies to understand this finding's impact on the risk of reinfection are warranted.

Are Patients With a History of Septic Arthritis Undergoing Total Knee Arthroplasty at Higher Risk for Revision Surgery? A Single-Center Study.

BACKGROUND: The decision to perform a total knee arthroplasty (TKA) on a previously infected knee is made complicated by the higher risk for both a periprosthetic joint infection (PJI) and early failure. There is currently no standard in the treatment strategy for this group of patients. We here report the outcomes of performing a primary TKA on patients with a prior septic knee arthritis. The aim of our study is to analyze the survival rates of patients with a history of septic arthritis undergoing TKA. METHODS: From 2010 to 2018, all patients treated in our institution with a minimum follow-up of 1 year, who have previous histories of knee joint infections and underwent a primary TKA were included in the study. All patients underwent the same surgical protocol and were given systemic and local antibiotic treatment. RESULTS: Of the 68 knees, there were 4 surgical revisions (5.9%). These included 2 septic revisions due to PJI (2.9%), 1 open arthrolysis for arthrofibrosis (1.5%), and 1 aseptic revision for implant loosening (1.5%). Sixty-four (64) knees (94%) had survived without any surgical interventions and the Kaplan-Meier analysis demonstrated an overall survivorship free from PJI of 97.1% at a mean of 5 years (range 1-9, standard deviation ±2.5 years). CONCLUSION: TKA is a suitable option for patients with a prior septic arthritis of the knee, provided that proper surgical technique and the utilization of systemic and local antibiotics are employed. LEVEL OF EVIDENCE: Level III, therapeutic study.

Comparative Genomic Analysis of Pseudomonas chlororaphis PCL1606 Reveals New Insight into Antifungal Compounds Involved in Biocontrol.

Pseudomonas chlororaphis PCL1606 is a rhizobacterium that has biocontrol activity against many soilborne phytopathogenic fungi. The whole genome sequence of this strain was obtained using the Illumina Hiseq 2000 sequencing platform and was assembled using SOAP denovo software. The resulting 6.66-Mb complete sequence of the PCL1606 genome was further analyzed. A comparative genomic analysis using 10 plant-associated strains within the fluorescent Pseudomonas group, including the complete genome of P. chlororaphis PCL1606, revealed a diverse spectrum of traits involved in multitrophic interactions with plants and microbes as well as biological control. Phylogenetic analysis of these strains using eight housekeeping genes clearly placed strain PCL1606 into the P. chlororaphis group. The genome sequence of P. chlororaphis PCL1606 revealed the presence of sequences that were homologous to biosynthetic genes for the antifungal compounds 2-hexyl, 5-propyl resorcinol (HPR), hydrogen cyanide, and pyrrolnitrin; this is the first report of pyrrolnitrin encoding genes in this P. chlororaphis strain. Single-, double-, and triple-insertional mutants in the biosynthetic genes of each antifungal compound were used to test their roles in the production of these antifungal compounds and in antagonism and biocontrol of two fungal pathogens. The results confirmed the function of HPR in the antagonistic phenotype and in the biocontrol activity of P. chlororaphis PCL1606.

Enhanced caveolin-1 expression increases migration, anchorage-independent growth and invasion of endometrial adenocarcinoma cells.

BACKGROUND: Caveolin-1 (CAV1) has been implicated both in tumor suppression and progression, whereby the specific role appears to be context dependent. Endometrial cancer is one of the most common malignancies of the female genital tract; however, little is known about the role of CAV1 in this disease. METHODS: Here, we first determined by immunohistochemistry CAV1 protein levels in normal proliferative human endometrium and endometrial tumor samples. Then using two endometrial cancer cell lines (ECC: Ishikawa and Hec-1A) we evaluated mRNA and protein levels of CAV1 by real time qPCR and Western blot analysis, respectively. The role of CAV1 expression in ECC malignancy was further studied by either inducing its expression in endometrial cancer cells with the tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate (4ß-TPA) or decreasing expression using short-hairpin RNA constructs, and then evaluating the effects of these changes on ECC proliferation, transmigration, matrigel invasion, and colony formation in soft agar. RESULTS: Immunohistochemical analysis of endometrial epithelia revealed that substantially higher levels of CAV1 were present in endometrial tumors than the normal proliferative epithelium. Also, in Ishikawa and Hec-1A endometrial cancer cells CAV1 expression was readily detectable. Upon treatment with 4ß-TPA CAV1 levels increased and coincided with augmented cell transmigration, matrigel invasion, as well as colony formation in soft agar. Reduction of CAV1 expression using short-hairpin RNA constructs ablated these effects in both cell types whether treated or not with 4ß-TPA. Alternatively, CAV1 expression appeared not to modulate significantly proliferation of these cells. CONCLUSION: Our study shows that elevated CAV1, observed in patients with endometrial cancer, is linked to enhanced malignancy of endometrial cancer cells, as evidenced by increased migration, invasion and anchorage-independent growth.

Survivin expression promotes VEGF-induced tumor angiogenesis via PI3K/Akt enhanced ß-catenin/Tcf-Lef dependent transcription.

Early in cancer development, tumour cells express vascular endothelial growth factor (VEGF), a secreted molecule that is important in all stages of angiogenesis, an essential process that provides nutrients and oxygen to the nascent tumor and thereby enhances tumor-cell survival and facilitates growth. Survivin, another protein involved in angiogenesis, is strongly expressed in most human cancers, where it promotes tumor survival by reducing apoptosis as well as favoring endothelial cell proliferation and migration. The mechanisms by which cancer cells induce VEGF expression and angiogenesis upon survivin up-regulation remain to be fully established. Since the PI3K/Akt signalling and ß-catenin-Tcf/Lef dependent transcription have been implicated in the expression of many cancer-related genes, including survivin and VEGF, we evaluated whether survivin may favor VEGF expression, release from tumor cells and induction of angiogenesis in a PI3K/Akt-ß-catenin-Tcf/Lef-dependent manner. Here, we provide evidence linking survivin expression in tumor cells to increased ß-catenin protein levels, ß-catenin-Tcf/Lef transcriptional activity and expression of several target genes of this pathway, including survivin and VEGF, which accumulates in the culture medium. Alternatively, survivin downregulation reduced ß-catenin protein levels and ß-catenin-Tcf/Lef transcriptional activity. Also, using inhibitors of PI3K and the expression of dominant negative Akt, we show that survivin acts upstream in an amplification loop to promote VEGF expression. Moreover, survivin knock-down in B16F10 murine melanoma cells diminished the number of blood vessels and reduced VEGF expression in tumors formed in C57BL/6 mice. Finally, in the chick chorioallantoid membrane assay, survivin expression in tumor cells enhanced VEGF liberation and blood vessel formation. Importantly, the presence of neutralizing anti-VEGF antibodies precluded survivin-enhanced angiogenesis in this assay. These findings provide evidence for the existance of a posititve feedback loop connecting survivin expression in tumor cells to PI3K/Akt enhanced ß-catenin-Tcf/Lef-dependent transcription followed by secretion of VEGF and angiogenesis.

darR and darS are regulatory genes that modulate 2-hexyl, 5-propyl resorcinol transcription in Pseudomonas chlororaphis PCL1606.

Pseudomonas chlororaphis PCL1606 synthesizes the antifungal antibiotic 2-hexyl, 5-propyl resorcinol (HPR), which is crucial for the biocontrol of fungal soil-borne pathogens. The genetic basis for HPR production lies in the dar genes, which are directly involved in the biosynthesis of HPR. In the present study, we elucidated the genetic features of the dar genes. Reverse transcription PCR experiments revealed an independent organization of the dar genes, except for darBC, which was transcribed as a polycistronic mRNA. In silico analysis of each gene revealed putative promoters and terminator sequences, validating the proposed gene arrangement. Moreover, experiments utilizing 5' rapid amplification of cDNA ends were used to determine the transcriptional initiation sites for the darA, darBC, darS and darR gene promoters, and subsequently to confirm the functionality of these regions. The results of quantitative real-time PCR experiments indicated that biosynthetic dar genes were not only modulated through the global regulator gacS, but also through darS and darR. The interplay between darS and darR revealed transcriptional cross-inhibition. However, these results also showed that other regulatory parameters play a role in HPR production, such as the environmental conditions and additional regulatory genes.

Histological changes in the retina provoked by lithium treatment in a nocturnal rodent (Lagostomus maximus maximus).

Daily morphological variations have been previously described in the viscacha (Lagostomus maximus maximus) retina. The aim of this work was to determine the effects of lithium administration on the histology of retinas from this nocturnal rodent since lithium is a drug that has been shown to affect different parameters of circadian rhythms. Adult male viscachas were divided into 2 groups, injected daily with lithium chloride or vehicle for 35 days, and sacrificed at 08:00, 16:00, and 24:00 h for light and electron microscopy studies. The following morphometric parameters were analyzed: the thickness of the photoreceptor layer, the rod outer and inner segments, and the outer nuclear layer. The control group displayed a true daily cycle of photoreceptor renewal similar to that previously reported by us for (untreated) viscachas in their normal habitat. In all lithium-treated groups, we did not observe histological changes in the thickness measurement of the retinal layers. In these groups, the retinas presented ultrastructural characteristics similar to those observed in control animals sacrificed at 24:00 h. In conclusion, chronic lithium administration abolished the daily histological rhythm in the viscacha retina, probably via inhibition of the phagocytosis process in pigment epithelial cells.

Review of Dohan Eherenfest et al. (2009) on "Classification of platelet concentrates: From pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF)".

This classic discusses the original publication of Dohan Eherenfest et al. on "Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF)", in which the authors propose four categories of platelet concentrates depending on their leucocyte and fibrin content (P-PRP, leucocyte- and platelet-rich plasma (L-PRP), pure platelet-rich fibrin (P-PRF), and L-PRF) to group a "jungle" of products in which the term platelet-rich plasma (PRP) was used indistinctly. They were able to identify common factors such as: (1) the use of anticoagulants and immediate centrifugation of the blood after its collection; (2) most preparation techniques allowed platelet concentrate preparation within an hour; (3) the centrifugation aimed to separate the blood in layers that would allow the extraction of specific fractions; and (4) the product was activated with thrombin or calcium chloride. The reviewed manuscript has been listed among the most cited PRP articles in regenerative medicine, with more than 800 citations, driving current scientific research and clinical practise by categorising L-PRP and P-PRP (now, leucocyte-poor PRP). The classification has also opened the door to understanding intrinsic biological mechanisms between platelets, leukocytes, fibrin, and growth factors, which will later be considered for studying the proliferation and differentiation of cells in different tissues affected by PRP. Since the initial classification of platelet concentrates, several other classification systems have been proposed and published in the current literature such as platelet, activation, white blood cell (PAW), Mishra, platelet, leucocyte, red blood cells, and activation (PLRA), dose of platelet, efficiency, purity, and activation (DEPA), method, activation, red blood cells, spin, platelets, image guidance, leukocytes, and light activation (MARSPILL), etc. These classifications have identified important aspects of PRP that affect the biological composition and, ultimately, the indications and outcomes. To date, there is still a lack of standardisation in sample preparation, cohort heterogeneity, and incomplete reporting of sample preparation utilised, leading to a lack of clarity and challenging researchers and clinicians.

The dar genes of Pseudomonas chlororaphis PCL1606 are crucial for biocontrol activity via production of the antifungal compound 2-hexyl, 5-propyl resorcinol.

To determine the genetic basis by which 2-hexyl, 5-propyl resorcinol (HPR) is produced by the biocontrol rhizobacterium Pseudomonas chlororaphis (formerly known as P. fluorescens) PCL1606, the presence and role of dar genes were investigated. To accomplish this aim, the pCGNOV-1 plasmid was isolated from a PCL1606 genomic library and was shown to hybridize to various dar probes by Southern blot. An analysis of the pCGNOV-1 genomic DNA revealed the presence of five open reading frames that were homologous to dar genes and had an organization that resembled the arrangement of previously described P. chlororaphis strains. Phylogenetic studies resulted in the clustering of PCL1606 with the P. chlororaphis subgroup, which supported the renaming of this strain from P. fluorescens to P. chlororaphis PCL1606. The construction of insertional mutants for each homologous dar gene in P. chlororaphis PCL1606 along with their corresponding complemented derivative strains restored HPR production and confirmed the key role of the dar A and darB genes in HPR production and in the antagonistic phenotype. Finally, biocontrol assays were performed on avocado-Rosellinia and tomato-Fusarium test systems using the HPR-defective and -complemented derivative strains generated here and demonstrated the crucial role of the biosynthetic dar genes in the biocontrol phenotype of P. chlororaphis PCL1606. This biocontrol phenotype is dependent on the dar genes via their production of the HPR antibiotic. Some of the dar genes not directly involved in the biosynthesis of HPR, such as darS or darR, might contribute to regulatory features of HPR production.

Patient Portals to Elicit Essential Patient-Reported Elements of Communication Supporting Person-Centered Oncologic Care: A Pilot Study of the PERSON Approach.

PURPOSE: Patient portal technology offers important new opportunities to support person-centered clinician-patient communication. METHODS: Questionnaires relating to understanding of illness and treatment intent were sent quarterly via portal to all patients scheduled for follow-up in GI medical oncology clinics. For patients in selected clinics, items eliciting health-related values were added. Patient responses were available to all oncology team members in the electronic health record. Workflow and content of clinician-patient discussions about illness, treatment, and care goals stayed within clinicians' discretion. Feasibility (patient response rate), patient understanding, acceptability (three-item patient questionnaire), and efficacy (quality of clinician communication) were evaluated. RESULTS: From May 2021 through December 2022, a total of 12,233 questionnaires about illness/treatment understanding were sent to 6,325 patients (one to six per patient), with 97% response, including 9,358 with both open- and closed-ended responses. Fewer than 0.1% of patients indicated distress related to the questionnaire/process. Open-ended responses complemented closed-ended answers by revealing prognostic awareness and illness concerns. Of 48 patients approached to complete the full questionnaire including values items via portal, 15 first received and completed them in clinic (5 on iPad, 10 on paper), while 33 received and 27 (82%) completed the portal questionnaire. Patients found the portal process acceptable, and ratings of clinician communication were higher after clinic visits informed by patients' questionnaire responses (average prescore 6.8 v 5.9 post; P = .03). CONCLUSION: Almost all patients in this large GI cancer cohort responded via the portal about their understanding of illness and treatment goals. Eliciting their personal values by portal was also feasible, accepted by patients, and improved patient ratings of clinicians' communication. Portals represent a promising tool for scaling assessment of essential patient-reported elements of person-centered communication.

Role of Oxidative Stress and Inflammation in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. It is related to several gestational and fetal adverse outcomes. Moreover, women with GDM and their infants have a high risk of developing type 2 diabetes in the future. The pathogenesis of GDM is not completely understood; nevertheless, two factors that contribute to its development are oxidative stress and inflammation. Oxidative stress and inflammation are related; reactive oxygen species (ROS) production can activate inflammatory cells and enhance the production of inflammatory mediators. Inflammation, in turn, leads to an increased ROS release, causing a vicious circle to ensue. Inflammatory responses can be achieved via the activation of the NF-κB signaling pathway. Herein, we review the English literature regarding oxidative stress and inflammation evaluated simultaneously in the same population, attempting to identify mechanisms through which these factors contribute to the development of GDM. Furthermore, the modulation of oxidative stress and inflammation by different therapies used in women with GDM and in cell models of GDM is included in the review. Probiotics and nutrient supplementations have been shown to reduce biomarkers of inflammation and oxidative stress in vitro and in women with GDM.

Micronutrient Deficiency Pre- and Post-bariatric Metabolic Surgery in Latin America: a Systematic Review.

BACKGROUND: Persons submitted to bariatric metabolic surgery present micronutrient deficiency before and after surgery, due to the lack of proper supplementation. The aim of this study is to establish the prevalence of micronutrient deficiency in people before and after bariatric metabolic surgery in Latin America. METHODS: This review was conducted in accordance with the 2020 PRISMA Guidelines. RESULTS: Twenty-seven studies and 2135 participants were included. The highest prevalence of deficiency before surgery was reported for vitamin D (74%), zinc (71%), and hemoglobin (62%); after surgery, they were vitamin A (90.6%), vitamin D (90%), and zinc (68%). CONCLUSIONS: There is a high prevalence of micronutrient deficiency before and after bariatric metabolic surgery from Latin American persons; the micronutrients with the highest deficiency prevalence were vitamin D before and vitamin A after bariatric metabolic surgery.

Genetic mapping of paternal sorting of mitochondria in cucumber.

Mitochondria are organelles that have their own DNA; serve as the powerhouses of eukaryotic cells; play important roles in stress responses, programmed cell death, and ageing; and in the vast majority of eukaryotes, are maternally transmitted. Strict maternal transmission of mitochondria makes it difficult to select for better-performing mitochondria, or against deleterious mutations in the mitochondrial DNA. Cucumber is a useful plant for organellar genetics because its mitochondria are paternally transmitted and it possesses one of the largest mitochondrial genomes among all eukaryotes. Recombination among repetitive motifs in the cucumber mitochondrial DNA produces rearrangements associated with strongly mosaic (MSC) phenotypes. We previously reported nuclear control of sorting among paternally transmitted mitochondrial DNAs. The goal of this project was to map paternal sorting of mitochondria as a step towards its eventual cloning. We crossed single plants from plant introduction (PI) 401734 and Cucumis sativus var. hardwickii and produced an F(2) family. A total of 425 F(2) plants were genotyped for molecular markers and testcrossed as the female with MSC16. Testcross families were scored for frequencies of wild-type versus MSC progenies. Discrete segregations for percent wild-type progenies were not observed and paternal sorting of mitochondria was therefore analyzed as a quantitative trait. A major quantitative trait locus (QTL; LOD >23) was mapped between two simple sequence repeats encompassing a 459-kb region on chromosome 3. Nuclear genes previously shown to affect the prevalence of mitochondrial DNAs (MSH1, OSB1, and RECA homologs) were not located near this major QTL on chromosome 3. Sequencing of this region from PI 401734, together with improved annotation of the cucumber genome, should result in the eventual cloning of paternal sorting of mitochondria and provide insights about nuclear control of organellar-DNA sorting.

Streptococcus pneumoniae serotype 19A in Latin America and the Caribbean: a systematic review and meta-analysis, 1990-2010.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) are in the process of implementation in Latin America. Experience in developed countries has shown that they reduce the incidence of invasive and non-invasive disease. However, there is evidence that the introduction of PCVs in universal mass vaccination programs, combined with inappropriate and extensive use of antibiotics, could be associated to changes in non-PCV serotypes, including serotype 19A. We conducted a systematic review to determine the distribution of serotype 19A, burden of pneumococcal disease and antibiotic resistance in the region. METHODS: We performed a systematic review of serotype 19A data from observational and randomized clinical studies in the region, conducted between 1990 and 2010, for children under 6 years. Pooled prevalence estimates from surveillance activities with confidence intervals were calculated. RESULTS: We included 100 studies in 22 countries and extracted data from 63. These data reported 19733 serotyped invasive pneumococcal isolates, 3.8% of which were serotype 19A. Serotype 19A isolates were responsible for 2.4% acute otitis media episodes, and accounted for 4.1% and 4.4% of 4,380 nasopharyngeal isolates from healthy children and in hospital-based/sick children, respectively. This serotype was stable over the twenty years of surveillance in the region. A total of 53.7% Spn19A isolates from meningitis cases and only 14% from non meningitis were resistant to penicillin. CONCLUSIONS: Before widespread PCV implementation in this region, serotype 19A was responsible for a relatively small number of pneumococcal disease cases. With increased use of PCVs and a greater number of serotypes included, monitoring S. pneumoniae serotype distribution will be essential for understanding the epidemiology of pneumococcal disease.

A Randomized Trial Evaluating Patient Experience and Preference Between Octreotide Long-Acting Release and Lanreotide for Treatment of Well-Differentiated Neuroendocrine Tumors.

PURPOSE: Somatostatin analogs octreotide long-acting release (octLAR) and lanreotide are equally acceptable in National Comprehensive Cancer Network guidelines for neuroendocrine tumors (NETs). Lanreotide is more expensive and given by deep subcutaneous injection, whereas octLAR is given intramuscularly. We evaluated patient preference between these agents in terms of injection site pain. MATERIALS AND METHODS: Randomized, single-blinded study. Patients with NETs received injections every 4 weeks. Arm 1: octLAR × 3, then lanreotide × 3; arm 2: reverse order. Self-reported injection site pain scores (range, 0-10) were obtained after each of the first three injections. Primary end point was comparison of mean pain scores over the first three injections. Secondary end points included patient-reported preference. RESULTS: Fifty-one patients enrolled (26 in arm 1 and 25 arm 2), all evaluable for primary end point. No significant difference was identified in the mean pain score over the first three injections (2.4 ± 1.9 v 1.9 ± 1.5, P = .5). Thirty-four of 51 (67%) patients (15 in arm 1 and 19 in arm 2) completed post-therapy questionnaires and were evaluable for secondary end points. Seven patients (47%) in arm 1 and eight patients (42%) in arm 2 indicated no drug preference at the end of treatment. In the other 19 patients, more patients indicated mild or strong preference for octLAR over lanreotide. CONCLUSION: We found minimal pain with octLAR and lanreotide and no significant pain score differences between the two. Patients indicating a drug preference trended toward favoring octLAR.