Review: Unveiling the effect of beta-nerve growth factor on the reproductive function in llamas and cows.

The actions of the beta-nerve growth factor (ß-NGF) on the neuroendocrine and reproductive system have challenged classical views on the control of reproductive function. After endometrial absorption, ß-NGF triggers ovulation and promotes the development of functional corpora lutea in camelids. In this article, we review evidence showing that, in camelids, ß-NGF exerts its actions by acting in both the hypothalamus and the ovary. In the hypothalamus, ß-NGF may induce gonadotropin-releasing hormone (GnRH) release by interacting with neurons or glial cells expressing receptors for ß-NGF. The LH surge occurs under the influence of ovarian estradiol and requires the release of GnRH into the portal vessels to reach the pituitary gland. In the ovary, ß-NGF may be promoting the differentiation of follicular to luteal cells by modifying the steroidogenic profile of ovarian follicular cells in both camelids and ruminants. Although the mechanisms for these actions are largely undetermined, we aim to offer an update on the current understanding of the effects of ß-NGF controlling reproductive function in camelids and ruminants.

Consensus-based recommendations on physical activity and exercise in patients with diabetes at risk of foot ulcerations: a Delphi study.

BACKGROUND: Patients with diabetes mellitus are exposed to important complications. Currently little evidence exist on the guidelines that these patients, at some risk of foot ulceration, should follow for physical exercise. OBJECTIVES: To reach a consensus among multidisciplinary and international experts on physical activity/exercise recommendations for patients with diabetes, according to foot ulcer risk. METHODS: Using a three-round Delphi method, a panel composed of 28 multidisciplinary experts in the management of diabetic foot assessed 109 recommendations on physical activity/exercise for patients with diabetes mellitus, according to their risk of foot ulcer. Consensus was assumed when 80% of responses matched the same category (agreement/disagreement). RESULTS: Twenty-nine experts participated in the first and second rounds of consultation, and twenty-eight did so in the third, reaching final agreement on 86 of the 109 recommendations considered (78.9%). The study, thus, generated a consensus set of recommendations concerning different aspects of diabetic footcare before, during, and after exercise (e.g. when to examine the foot, how to assess it, what type of sock and insole to use, what types of exercise to perform, and when it is advisable to return to activity after an ulceration). CONCLUSION: This Delphi study generated recommendations based on the consensus of international experts on physical activity and exercise by patient with diabetes at risk of ulceration. Recommendations considered the state of the foot and the patient's history and status before physical activity and included information on intensity, duration, frequency, and progressions of physical activity/exercise, and the use of custom-made plantar orthoses, shoe prescription, and the convenience of returning to physical activity after an ulceration.

Trends in premature mortality from diabetes mellitus in Costa Rica in the period 2000-2020.

OBJECTIVES: To analyze the temporal trends of premature mortality from diabetes in Costa Rica in the period 2000-2020, at a national level and by province, and the effect of the COVID-19 pandemic on diabetes mortality during the year 2020. METHODS: We studied the temporal trends of mortality from diabetes in Costa Rica in the period between 2000 and 2020. Age-standardized mortality rates and corresponding 95% confidence intervals were calculated for each year, sex and province. RESULTS: We analyzed the data of 17,968 deceased persons. The mean age was 72.5 years (range 1 to 109 years), and 51.5% of the population (n = 9253) was younger than 75 years. In both men and women, we observed a significant decrease in mortality from 2000 to 2014, followed by the opposite trend from 2014 to 2020, with average yearly increases of 13.9% in men and 11.6% in women. CONCLUSIONS: Premature mortality from diabetes has been growing from 2014. The COVID-19 pandemic changed the mortality pattern, increasing premature diabetes deaths in Costa Rica in 2020.

p53 Related Protein Kinase is Required for Arp2/3-Dependent Actin Dynamics of Hemocytes in Drosophila melanogaster.

Cells extend membrane protrusions like lamellipodia and filopodia from the leading edge to sense, to move and to form new contacts. The Arp2/3 complex sustains lamellipodia formation, and in conjunction with the actomyosin contractile system, provides mechanical strength to the cell. Drosophila p53-related protein kinase (Prpk), a Tsc5p ortholog, has been described as essential for cell growth and proliferation. In addition, Prpk interacts with proteins associated to actin filament dynamics such as α-spectrin and the Arp2/3 complex subunit Arpc4. Here, we investigated the role of Prpk in cell shape changes, specifically regarding actin filament dynamics and membrane protrusion formation. We found that reductions in Prpk alter cell shape and the structure of lamellipodia, mimicking the phenotypes evoked by Arp2/3 complex deficiencies. Prpk co-localize and co-immunoprecipitates with the Arp2/3 complex subunit Arpc1 and with the small GTPase Rab35. Importantly, expression of Rab35, known by its ability to recruit upstream regulators of the Arp2/3 complex, could rescue the Prpk knockdown phenotypes. Finally, we evaluated the requirement of Prpk in different developmental contexts, where it was shown to be essential for correct Arp2/3 complex distribution and actin dynamics required for hemocytes migration, recruitment, and phagocytosis during immune response.

Uso de vasopresina y suturas transfixivas para el tratamiento quirúrgico de la gestación ectópica intersticial / Use of vasopressin and transfixive sutures for the surgical treatment of interstitial ectopic gestation

Resumen La gestación cornual, también conocida como intersticial, es una gestación ectópica infrecuente que ocurre en 1/2500 a 1/5000 de los embarazos cuando el embrión implanta en el trayecto intramiometrial de la porción proximal de la trompa. Puede debutar como shock hipovolémico en un 25% de los casos, conllevando una mortalidad de hasta un 2,5%. Mediante ecografía se encuentra un saco gestacional excéntrico y rodeado por una fina capa de miometrio. El tratamiento, en la mayoría de los casos, es quirúrgico, y el control de la hemostasia supone todo un reto. Se presentan dos casos clínicos de mujeres con diagnóstico de gestación intersticial en quienes se realizó exéresis por laparoscopia tras inyección de vasopresina, permitiendo así controlar el sangrado. En una de las pacientes se practicaron también puntos transfixivos transitorios en la arteria uterina y el ligamento útero-ovárico.

Abstract Cornual gestation, also known as interstitial, is a rare ectopic gestation that occurs in 1/2500 to 1/5000 of pregnancies when the embryo implants in the intramyometrial tract of the proximal tube. It can debut as hypovolemic shock in 25% of cases, leading to a mortality rate of up to 2.5%. Using ultrasound, we will find an eccentric gestational sac surrounded by a thin layer of myometrium. Treatment, in most cases, is surgical and control of hemostasis is a challenge. Two clinical cases are presented of women with a diagnosis of interstitial pregnancy in whom transient transfixive sutures were performed at the level of the uterine artery and uterine-ovarian ligament and injection of vasopressin prior to laparoscopic exeresis, thus allowing the bleeding to be controlled.

Bone Marrow Adiposity in Premenopausal Women With Type 2 Diabetes With Observations on Peri-Trabecular Adipocytes.

CONTEXT: No study has yet evaluated the relationships among bone marrow adiposity (BMA), bone histomorphometry (BH), and glycemic control in premenopausal women with type 2 diabetes (T2DM). OBJECTIVE: We aimed to assess the effect of glycemic control on BMA, correlate the parameters of BH with BMA, and correlate BMA with the use of hypoglycemic agents and with bone mineral density (BMD). METHODS: This was a cross-sectional study that evaluated 26 premenopausal women with T2DM who were divided into groups with HbA1c < 7% (good control [GC], n = 10) and HbA1c > 7% (poor control [PC], n = 16). BMA parameters (adipocyte number [Ad.N], total adipocyte perimeter [Ad.Pm], total adipocyte area [Ad.Ar], percentage adipocyte volume per marrow volume [Ad.V/Ma.V]) and peri-trabecular adipocyte number divided by bone surface (Ad.N/BS) were evaluated. BH static (bone volume fraction [BV/TV], osteoid thickness [O.Th], osteoid surface/bone surface [OS/BS]) and dynamic parameters and serum insulin-like growth factor-1 were measured. BMA data were compared between the GC and PC groups. Correlations were performed. RESULTS: Ad.N, Ad.Pm, and Ad.Ar were higher in PC (all, P = 0.04). HbA1c correlated positively with Ad.N/BS (P < 0.01) and Ad.N/BS correlated negatively with O.Th (P < 0.01) and OS/BS (P = 0.02). Positive and negative correlations were observed between insulin and metformin use, respectively, with all adipocyte parameters except Ad.N/BS (P < 0.05). Structural parameters were negatively correlated with the BMA. BMD of the femoral neck (r = -549, P < 0.01) and total femur (r = -0.502, P < 0.01) were negatively correlated with Ad.V/Ma.V. CONCLUSION: Poor glycemic control is associated with hyperplasia and hypertrophy of BMAs and with lower BV/TV. Ad.N/BS, a new BMA parameter, is correlated with HbA1c and negatively with O.Th. The use of insulin seems to stimulate the expansion of BMA while that of metformin has the opposite effect. These findings suggest that the increase in BMA may play a role in the T2DM bone disease; on the other hand, good glycemic control might help prevent it.

Dosimetric impact of rectum and bladder anatomy and intrafractional prostate motion on hypofractionated prostate radiation therapy.

OBJECTIVE: The objective of this study was to evaluate the dosimetric impact on hypofractionated prostate radiation therapy of two geometric uncertainty sources: rectum and bladder filling and intrafractional prostate motion. MATERIALS AND METHODS: This prospective study included 544 images (375 pre-treatment cone-beam CT [CBCT] and 169 post-treatment CBCT) from 15 prostate adenocarcinoma patients. We recalculated the dose on each pre-treatment CBCT once the positioning errors were corrected. We also recalculated two dose distributions on each post-treatment CBCT, either using or not intrafractional motion correction. A correlation analysis was performed between CBCT-based dose and rectum and bladder filling as well as intrafraction prostate displacements. RESULTS: No significant differences were found between administered and planned rectal doses. However, we observed an increase in bladder dose due to a lower bladder filling in 66% of treatment fractions. These differences were reduced at the end of the fraction since the lower bladder volume was compensated by the filling during the treatment session. A statistically significant reduction in target volume coverage was observed in 27% of treatment sessions and was correlated with intrafractional prostate motion in sagittal plane > 4 mm. CONCLUSIONS: A better control of bladder filling is recommended to minimize the number of fractions in which the bladder volume is lower than planned. Fiducial mark tracking with a displacement threshold of 5 mm in any direction is recommended to ensure that the prescribed dose criteria are met.

A Review of Technologies and Techniques for Indoor Navigation Systems for the Visually Impaired.

Technologies and techniques of location and navigation are advancing, allowing greater precision in locating people in complex and challenging conditions. These advances have attracted growing interest from the scientific community in using indoor positioning systems (IPSs) with a higher degree of precision and fast delivery time, for groups of people such as the visually impaired, to some extent improving their quality of life. Much research brings together various works that deal with the physical and logical approaches of IPSs to give the reader a more general view of the models. These surveys, however, need to be continuously revisited to update the literature on the features described. This paper presents an expansion of the range of technologies and methodologies for assisting the visually impaired in previous works, providing readers and researchers with a more recent version of what was done and the advantages and disadvantages of each approach to guide reviews and discussions about these topics. Finally, we discuss a series of considerations and future trends for the construction of indoor navigation and location systems for the visually impaired.

Heterologous production of the epoxycarotenoid violaxanthin in Saccharomyces cerevisiae.

Microbial production of carotenoids has mainly focused towards a few products, such as ß-carotene, lycopene and astaxanthin. However, other less explored carotenoids, like violaxanthin, have also shown unique properties and promissory applications. Violaxanthin is a plant-derived epoxidated carotenoid with strong antioxidant activity and a key precursor of valuable compounds, such as fucoxanthin and ß-damascenone. In this study, we report for the first time the heterologous production of epoxycarotenoids in yeast. We engineered the yeast Saccharomyces cerevisiae following multi-level strategies for the efficient accumulation of violaxanthin. Starting from a ß-carotenogenic yeast strain, we first evaluated the performance of several ß-carotene hydroxylases (CrtZ), and zeaxanthin epoxidases (ZEP) from different species, together with their respective N-terminal truncated variants. The combined expression of CrtZ from Pantoea ananatis and truncated ZEP of Haematococcus lacustris showed the best performance and led to a yield of 1.6 mg/gDCW of violaxanthin. Further improvement of the epoxidase activity was achieved by promoting the transfer of reducing equivalents to ZEP by expressing several redox partner systems. The co-expression of the plant truncated ferredoxin-3, and truncated root ferredoxin oxidoreductase-1 resulted in a 2.2-fold increase in violaxanthin yield (3.2 mg/gDCW). Finally, increasing gene copy number of carotenogenic genes enabled reaching a final production of 7.3 mg/gDCW in shake flask cultures and batch bioreactors, which is the highest yield of microbially produced violaxanthin reported to date.

Genomic integration of unclonable gene expression cassettes in Saccharomyces cerevisiae using rapid cloning-free workflows.

Most DNA assembly methods require bacterial amplification steps, which restrict its application to genes that can be cloned in the bacterial host without significant toxic effects. However, genes that cannot be cloned in bacteria do not necessarily exert toxic effects on the final host. In order to tackle this issue, we adapted two DNA assembly workflows for rapid, cloning-free construction and genomic integration of expression cassettes in Saccharomyces cerevisiae. One method is based on a modified Gibson assembly, while the other relies on a direct assembly and integration of linear PCR products by yeast homologous recombination. The methods require few simple experimental steps, and their performance was evaluated for the assembly and integration of unclonable zeaxanthin epoxidase expression cassettes in yeast. Results showed that up to 95% integration efficiency can be reached with minimal experimental effort. The presented workflows can be employed as rapid gene integration tools for yeast, especially tailored for integrating unclonable genes.

Bone Histomorphometry in Young Patients With Type 2 Diabetes is Affected by Disease Control and Chronic Complications.

CONTEXT: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of fractures. No study has evaluated the correlation of bone histomorphometry (BH) parameters with glycemic control and presence of chronic complications (CCs) in premenopausal women with T2DM. OBJECTIVES: To evaluate BH and correlate them with the degree of glycemic control and presence of CCs. DESIGN, SETTINGS, AND PATIENTS: This was a cross-sectional study conducted at a tertiary medical center. Twenty-six premenopausal women with T2DM were divided into groups with glycated hemoglobin HbA1c < 7% (good control, GC; n = 10) and HbA1c > 7% (poor control, PC; n = 16), and further subdivided into groups with (n = 9) and without (n = 17) CCs. BH parameters (bone volume [bone volume per total volume, BV/TV], trabecular thickness [Tb.Th], trabecular number [Tb.N], trabecular separation [Tb.Sp], osteoid thickness [O.Th], osteoid surface [osteoid surface per bone surface, OS/BS]), mineralizing surface [MS/BS], bone formation rate [BFR]), mineral apposition rate [MAR]) as well as serum pentosidine (PEN) and insulin-like growth factor (IGF)-1 were measured. The BH data were compared among the groups and with a BH control group (control group, CG, n = 15) matched by age, sex, and race. RESULTS: BV/TV was increased in GC (P < .001) and PC (P = .05) groups and O.th (P = .03) was smaller in the PC group than in the CG. A comparison of the groups with and without CCs with the CG showed in the group with CCs, O.Th was smaller(P = .01) and BV/TV similar to the CG (P = .11). HbA1c correlated negatively with O.Th (P = .02) and OS/BS (P = .01). There was no correlation of BH to PEN and IGF-1. CONCLUSION: BH in premenopausal patients with T2DM is affected by disease control and chronic complications.

Build Your Bioprocess on a Solid Strain-ß-Carotene Production in Recombinant Saccharomyces cerevisiae.

Robust fermentation performance of microbial cell factories is critical for successful scaling of a biotechnological process. From shake flask cultivations to industrial-scale bioreactors, consistent strain behavior is fundamental to achieve the production targets. To assert the importance of this feature, we evaluated the impact of the yeast strain design and construction method on process scalability -from shake flasks to bench-scale fed-batch fermentations- using two recombinant Saccharomyces cerevisiae strains capable of producing ß-carotene; SM14 and ßcar1.2 strains. SM14 strain, obtained previously from adaptive evolution experiments, was capable to accumulate up to 21 mg/gDCW of ß-carotene in 72 h shake flask cultures; while the ßcar1.2, constructed by overexpression of carotenogenic genes, only accumulated 5.8 mg/gDCW of carotene. Surprisingly, fed-batch cultivation of these strains in 1L bioreactors resulted in opposite performances. ßcar1.2 strain reached much higher biomass and ß-carotene productivities (1.57 g/L/h and 10.9 mg/L/h, respectively) than SM14 strain (0.48 g/L/h and 3.1 mg/L/h, respectively). Final ß-carotene titers were 210 and 750 mg/L after 80 h cultivation for SM14 and ßcar1.2 strains, respectively. Our results indicate that these substantial differences in fermentation parameters are mainly a consequence of the exacerbated Crabtree effect of the SM14 strain. We also found that the strategy used to integrate the carotenogenic genes into the chromosomes affected the genetic stability of strains, although the impact was significantly minor. Overall, our results indicate that shake flasks fermentation parameters are poor predictors of the fermentation performance under industrial-like conditions, and that appropriate construction designs and performance tests must be conducted to properly assess the scalability of the strain and the bioprocess.

Maternal periodontitis and preterm birth: Systematic review and meta-analysis.

AIM: To assess the association between periodontitis and preterm birth in women of childbearing age. MATERIALS AND METHODS: This review included analytical case-control studies and prospective cohort studies evaluating the association between maternal periodontitis and preterm birth. Of the 3104 screened articles, 31 met the inclusion criteria for the review, and 20 met the quality criteria. The selected studies included a total of 10 215 women. RESULTS: Twenty articles contributed to the meta-analysis; 16 used a case-control design, and 4 were prospective cohort studies. The study heterogeneity was low (Q = 24.2464; P = 0.1869; I2  = 21.63%). A positive association between maternal periodontitis and preterm birth was found in 60% of the studies. Under the random-effects model, meta-analysis gave an odds ratio (OR) of 2.01 (95% CI 1.71, 2.36), representing a significant positive association between the explanatory and outcome variables. CONCLUSION: Pregnant mothers with periodontitis double the risk of preterm birth. There is a lack of international consensus for diagnosing maternal periodontitis.

Impact of rectum and bladder anatomy in intrafractional prostate motion during hypofractionated radiation therapy.

BACKGROUND: The objective was to determine the magnitude of the prostate intrafractional motion relative to bony pelvis anatomy, and to evaluate the relationship between this displacement and some clinical and anatomical variables. MATERIALS AND METHODS: The prospective study consisted of 544 images (375 pre-treatment CBCT and 169 post-treatment CBCT) from 15 prostate adenocarcinoma patients that were used for intrafractional prostate motion determination. In addition, two radiation oncologists re-contoured the bladder and rectum on each CBCT according to the patient's anatomy of the day. ANOVA and correlation analysis followed by linear regression analysis were performed to identify clinical or anatomical variables that predict large prostate intrafractional motion. RESULTS: Prostate shift increased in patients with hormone therapy (p ≤ 0.02). The regression analysis showed that patients with large bladder intrafractional filling (p < 0.01) and a large bladder volume difference from planning CT were more likely to experience bigger longitudinal prostate motion (> 3 mm). Recommended bladder size values: anterior-posterior size ≤ 10 cm and anterior-posterior/cranio-caudal ratio ≤ 1.7, both parameters measured in the midsagittal prostate plane, were defined. CONCLUSIONS: The treatment margin should not be reduced for those patients who were treated with hormone therapy and/or whose rectum or bladder was far from complying the preparation protocol conditions.

Reduced late urinary toxicity with high-dose intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer.

BACKGROUND/PURPOSE: To evaluate the impact of intensity-modulated radiotherapy (IMRT) with intra-prostate fiducial markers image-guided radiotherapy (IGRT) on the incidence of late urinary toxicity compared to 3D conformal radiotherapy (3DCRT) for patients with prostate cancer (PC). METHODS AND MATERIALS: We selected 733 consecutive patients with localized PC treated with dose-escalation radiotherapy between 2001 and 2014. Eligibility criteria were radiation dose >72.0 Gy, no pelvic RT and minimum follow-up 24 months. 438 patients were treated with 3DCRT and 295 with IMRT. Acute and late urinary complications were assessed using the EORTC/RTOG and CTCAEs v3.0 definition. The Cox regression model was used to compare grade ≥2 urinary toxicity between both techniques. The median follow-up was 75 months (range 24-204). RESULTS: The median isocenter radiation dose was 78.7 Gy for 3DCRT and 80.7 Gy for IMRT/IGRT (p < 0.001). The 5-year incidence of late grade ≥2 urinary toxicity was 6.4% for IMRT and 10.8% for 3DCRT [hazard ratio (HR) 0.575, p = 0.056]. The corresponding 5-year estimates of late grade ≥2 hematuria were 2% for IMRT and 5.3% for 3DCRT (HR 0.296, p = 0.024). On multivariate analysis, the antecedent of prior transurethral resection of the prostate was also a strong predictor of a higher risk of urinary complications (HR 2.464, p = 0.002) and of hematuria (HR 5.196, p < 0.001). CONCLUSION: Compared with 3DCRT, high-dose IMRT/IGRT is associated with a lower rate of late urinary complications in spite of higher radiation dose.

Chemical vs. biotechnological synthesis of C13-apocarotenoids: current methods, applications and perspectives.

Apocarotenoids are natural compounds derived from the oxidative cleavage of carotenoids. Particularly, C13-apocarotenoids are volatile compounds that contribute to the aromas of different flowers and fruits and are highly valued by the Flavor and Fragrance industry. So far, the chemical synthesis of these terpenoids has dominated the industry. Nonetheless, the increasing consumer demand for more natural and sustainable processes raises an interesting opportunity for bio-production alternatives. In this regard, enzymatic biocatalysis and metabolically engineered microorganisms emerge as attractive biotechnological options. The present review summarizes promising bioengineering approaches with regard to chemical production methods for the synthesis of two families of C13-apocarotenoids: ionones/dihydroionones and damascones/damascenone. We discuss each method and its applicability, with a thorough comparative analysis for ionones, focusing on the production process, regulatory aspects, and sustainability.

Genomic prediction in biparental tropical maize populations in water-stressed and well-watered environments using low-density and GBS SNPs.

One of the most important applications of genomic selection in maize breeding is to predict and identify the best untested lines from biparental populations, when the training and validation sets are derived from the same cross. Nineteen tropical maize biparental populations evaluated in multienvironment trials were used in this study to assess prediction accuracy of different quantitative traits using low-density (~200 markers) and genotyping-by-sequencing (GBS) single-nucleotide polymorphisms (SNPs), respectively. An extension of the Genomic Best Linear Unbiased Predictor that incorporates genotype × environment (GE) interaction was used to predict genotypic values; cross-validation methods were applied to quantify prediction accuracy. Our results showed that: (1) low-density SNPs (~200 markers) were largely sufficient to get good prediction in biparental maize populations for simple traits with moderate-to-high heritability, but GBS outperformed low-density SNPs for complex traits and simple traits evaluated under stress conditions with low-to-moderate heritability; (2) heritability and genetic architecture of target traits affected prediction performance, prediction accuracy of complex traits (grain yield) were consistently lower than those of simple traits (anthesis date and plant height) and prediction accuracy under stress conditions was consistently lower and more variable than under well-watered conditions for all the target traits because of their poor heritability under stress conditions; and (3) the prediction accuracy of GE models was found to be superior to that of non-GE models for complex traits and marginal for simple traits.