Mitochondrial complex I activity in microglia sustains neuroinflammation.

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.

Postnatal genetic and neurodevelopmental assessment in infants born at term with severely low birth weight of non-placental origin.

OBJECTIVE: To determine the frequency of genetic syndromes and childhood neurodevelopmental impairment in non-malformed infants born at term with severely low birth weight and no evidence of placental insufficiency. METHODS: This case series was constructed from the data of infants delivered at term between 2013 and 2018 with severely low birth weight, defined as birth weight more than 2.5 SD below the mean, with normal maternal and fetal Doppler (umbilical artery, fetal middle cerebral artery, cerebroplacental ratio and uterine artery) and no maternal hypertensive disorder during pregnancy or fetal structural anomaly on prenatal ultrasound examination. Clinical exome sequencing and copy number variation (CNV) analysis were performed using DNA extracted from the children's saliva. Cognitive and psychomotor development was evaluated using the Bayley Scales of Infant and Toddler Development, 3rd edition or the Wechsler Intelligence Scale for Children, 5th edition tests, according to the child's age at testing. RESULTS: Among the 36 405 infants born within the study period, 274 (0.75%) had a birth weight below -2.5 SD, of whom 98 met the inclusion criteria. Among the 63 families contacted, seven (11%) reported a postnatal diagnosis of a genetic syndrome and a further 18 consented to participate in the study. Median gestational age at delivery was 38.0 (interquartile range (IQR), 37.3-38.5) weeks and median birth weight was 2020 (IQR, 1908-2248) g. All 18 children showed a normal result on clinical exome sequencing and CNV analysis, but six (33%) obtained a low score on neurodevelopmental testing. CONCLUSION: Non-malformed severely small term infants with no clinical or Doppler signs of placental insufficiency present a high rate of genetic syndromes and neurodevelopmental impairment during childhood. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Characterization of a Ferryl Flip in Electronically Tuned Nonheme Complexes. Consequences in Hydrogen Atom Transfer Reactivity.

Two oxoiron(IV) isomers (R 2a and R 2b) of general formula [FeIV (O)(R PyNMe3 )(CH3 CN)]2+ are obtained by reaction of their iron(II) precursor with NBu4 IO4 . The two isomers differ in the position of the oxo ligand, cis and trans to the pyridine donor. The mechanism of isomerization between R 2a and R 2b has been determined by kinetic and computational analyses uncovering an unprecedented path for interconversion of geometrical oxoiron(IV) isomers. The activity of the two oxoiron(IV) isomers in hydrogen atom transfer (HAT) reactions shows that R 2a reacts one order of magnitude faster than R 2b, which is explained by a repulsive noncovalent interaction between the ligand and the substrate in R 2b. Interestingly, the electronic properties of the R substituent in the ligand pyridine ring do not have a significant effect on reaction rates. Overall, the intrinsic structural aspects of each isomer define their relative HAT reactivity, overcoming changes in electronic properties of the ligand.

Assessing the viability of recovered phosphorus from eutrophicated aquatic ecosystems as a liquid fertilizer.

One of the most important worldwide environmental challenges is the alteration of the biogeochemical cycle of phosphorus (P). P is globally exported from terrestrial to aquatic ecosystems, causing the eutrophication of the receiving waters. In this context, magnetic microparticles (MPs) have been recently proposed for trapping P in natural eutrophicated ecosystems, as well as in treated wastewaters. The main advantage of using MPs is that both P and MPs can be recovered from the treated water. Thus, the working hypothesis of the present study is that P can be desorbed from P-loaded MPs and recovered P can be later used as a fertilizer. To test this hypothesis, the best working conditions for desorbing P from P-loaded MPs were identified; then, an experiment with different plant nutrient solutions (neutralized solutions containing recovered P and an unfertilized control) was carried out with three different plant species: Ocimum basilicum L., Cucumis sativus L. and Cucumis melo L. Finally, germination, height, root and shoot biomass and P concentration in root and shoot were compared among treatments. Our results show that the best conditions for P desorption from P-loaded MPs occurred when using 0.1 M NH4OH and using H3PO4 for neutralizing pH. The greenhouse fertirrigation pot experiment showed that the neutralized solution containing desorbed P from P-loaded MPs can be used as a liquid fertilizer, since its combination with macro and microelements significantly increased plant height, growth rate, shoot and root biomass and shoot and root P concentration. As a result, MPs can be proposed to be used for counteracting the widespread and coupled problems of the exhaustion of the P reserves and the eutrophication of aquatic ecosystems.

Electrodeposition of plasmonic bimetallic Ag-Cu nanodendrites and their application as surface-enhanced Raman spectroscopy (SERS) substrates.

Plasmonic bimetallic Ag-Cu nanodendrites were synthesized by an electrodeposition process and their potential as surface-enhanced Raman scattering (SERS) substrates was studied. We demonstrated a facile and efficient way for the preparation of highly sensitive SERS substrates. The electrodeposition time was an important parameter in the formation of Ag-Cu dendrites onto the Al sheet. The Ag-Cu dendrites showed an excellent response detecting Rhodamine 6 G at ultra-low concentrations such as 1 × 10-15 mol l-1. This Ag-Cu substrate possesses an excellent SERS activity and it could be used for the detection of molecules at trace level. This electrodeposition process could be extended for the fabrication of other plasmonic bimetallic dendrites.

Ligand-dependent Hedgehog pathway activation in Rhabdomyosarcoma: the oncogenic role of the ligands.

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. The Hedgehog (HH) pathway is known to develop an oncogenic role in RMS. However, the molecular mechanism that drives activation of the pathway in RMS is not well understood. METHODS: The expression of HH ligands was studied by qPCR, western blot and immunohistochemistry. Functional and animal model studies were carried out with cells transduced with shRNAs against HH ligands or treated with HH-specific inhibitors (Vismodegib and MEDI-5304). Finally, the molecular characterisation of an off-target effect of Vismodegib was also made. RESULTS: The results showed a prominent expression of HH ligands supporting an autocrine ligand-dependent activation of the pathway. A comparison of pharmacologic Smoothened inhibition (Vismodegib) and HH ligand blocking (MEDI-5304) is also provided. Interestingly, a first description of pernicious off-target effect of Vismodegib is also reported. CONCLUSIONS: The clarification of the HH pathway activation mechanism in RMS opens a door for targeted therapies against HH ligands as a possible alternative in the future development of better treatment protocols. Moreover, the description of a pernicious off-target effect of Vismodegib, via unfolded protein response activation, may mechanistically explain its previously reported inefficiency in several ligand-dependent cancers.

Composite infrared spectrometer (CIRS) on Cassini.

The Cassini spacecraft orbiting Saturn carries the composite infrared spectrometer (CIRS) designed to study thermal emission from Saturn and its rings and moons. CIRS, a Fourier transform spectrometer, is an indispensable part of the payload providing unique measurements and important synergies with the other instruments. It takes full advantage of Cassini's 13-year-long mission and surpasses the capabilities of previous spectrometers on Voyager 1 and 2. The instrument, consisting of two interferometers sharing a telescope and a scan mechanism, covers over a factor of 100 in wavelength in the mid and far infrared. It is used to study temperature, composition, structure, and dynamics of the atmospheres of Jupiter, Saturn, and Titan, the rings of Saturn, and surfaces of the icy moons. CIRS has returned a large volume of scientific results, the culmination of over 30 years of instrument development, operation, data calibration, and analysis. As Cassini and CIRS reach the end of their mission in 2017, we expect that archived spectra will be used by scientists for many years to come.

Composite infrared spectrometer (CIRS) on Cassini: publisher's note.

This publisher's note renumbers the reference list in Appl. Opt.56, 5274 (2017)APOPAI0003-693510.1364/AO.56.005274.

Maternal, fetal and perinatal alterations associated with obesity, overweight and gestational diabetes: an observational cohort study (PREOBE).

BACKGROUND: Maternal overweight, obesity, and gestational diabetes (GD) have been negatively associated with offspring development. Further knowledge regarding metabolic and nutritional alterations in these mother and their offspring are warranted. METHODS: In an observational cohort study we included 331 pregnant women from Granada, Spain. The mothers were categorized into four groups according to BMI and their GD status; overweight (n:56), obese (n:64), GD (n:79), and healthy normal weight controls (n:132). We assessed maternal growth and nutritional biomarkers at 24 weeks (n = 269), 34 weeks (n = 310) and at delivery (n = 310) and the perinatal characteristics including cord blood biomarkers. RESULTS: Obese and GD mothers had significantly lower weight gain during pregnancy and infant birth weight, waist circumference, and placental weight were higher in the obese group, including a significantly increased prevalence of macrosomia. Except for differences in markers of glucose metabolism (glucose, HbA1c, insulin and uric acid) we found at some measures that overweight and/or obese mothers had lower levels of transferrin saturation, hemoglobin, Vitamin B12 and folate and higher levels of C-reactive protein, erythrocyte sedimentation rate, ferritin, and cortisol. GD mothers had similar differences in hemoglobin and C-reactive protein but higher levels of folate. The latter was seen also in cord blood. CONCLUSIONS: We identified several metabolic alterations in overweight, obese and GD mothers compared to controls. Together with the observed differences in infant anthropometrics, these may be important biomarkers in future research regarding the programming of health and disease in children. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov, identifier ( NCT01634464 ).

Analysis of risk factors for hydrocephalus development in newborn infants with germinal matrix hemorrhage.

AIM: The aim of this study was to analyze risk factors for the development of hydrocephalus in newborn infants with germinal matrix (GM) hemorrhage. METHODS: The study comprised 271 patients admitted to Carlos Haya University Hospital in Malaga with GM hemorrhage. The following data were recorded: gestational age, gender, twin birth, head circumference at birth, weight at birth, and Papile grade. Severe obstetrical (abruption, chorioamnionitis, pregnancy-induced hypertension, tocolytic treatment) and neonatal disorders (respiratory distress syndrome, neonatal infection, coagulation disorder, patent ductus arteriosus, necrotizing enterocolitis) were also recorded. Symptomatic hydrocephalus was diagnosed in the event of a progressive increase in head circumference and ventricular indices requiring shunting. RESULTS: Of the 271 patients, 139 (51%) developed posthemorrhagic ventriculomegaly; 47 patients (17%) developed symptomatic hydrocephalus and needed shunt implantation. We found a significant relationship between the development of symptomatic hydrocephalus and Papile grade, lower gestational age, lower birth weight, twin birth, and neonatal infection. CONCLUSION: Awareness of risk factors for the development of hydrocephalus in newborn infants with GM hemorrhage should be emphasized in order to enable an early diagnosis of ventriculomegaly and symptomatic hydrocephalus and thus make a correct therapeutic decision.

Re-conceptualizing Neurosis as a Degree of Egocentricity: Ethical Issues in Psychological Theory.

Psychology's historical rejection of ethics has led to an oversimplification of the origins and treatments of mental disorders. In this article, we present an analysis of how classical neurosis can be reformulated from an ethical and psychological interaction. We focus on the crucial role that egocentricity plays and argue that this term can help to clarify how ego defensive ethical decisions can undermine psychological capacities and contribute to a progressive depersonalization that can result in typical clinical disorders. In Christian anthropology, the virtues, especially humility and love have a crucial role in the positive growth of human affective and cognitive capacities. In addition, the person in his/her nature is endowed with the capacity to transcend the self and to escape egocentricity through self-giving love of God and of others. This capacity of self-giving is diametrically opposed to egocentricity and opens a new way for possible psychological recovery.

Are women with a history of abuse more vulnerable to perinatal depressive symptoms? A systematic review.

The objective of this paper is to examine the association between maternal lifetime abuse and perinatal depressive symptoms. Papers included in this review were identified through electronic searches of the following databases: Pubmed Medline and Ovid, EMBASE, PsycINFO, and the Cochrane Library. Each database was searched from its start date through 1 September 2011. Keywords such as "postpartum," "perinatal," "prenatal," "depression," "violence," "child abuse," and "partner abuse" were included in the purview of MeSH terms. Studies that examined the association between maternal lifetime abuse and perinatal depression were included. A total of 545 studies were included in the initial screening. Forty-three articles met criteria for inclusion and were incorporated in this review. Quality of articles was evaluated with the Newcastle-Ottawa-Scale (NOS). This systematic review indicates a positive association between maternal lifetime abuse and depressive symptoms in the perinatal period.

A new de novo mutation in a non-hot spot region at the DMD gene in a Mexican family.

In this report we present the analysis of a sporadic case of DMD and his family. In the present case, a deletion of exons 18-47 is presented which predicts abolition of the reading frame and is located between the well-known deletion hot spots of the DMD gene. This mutation was not previously reported in the Leiden database (LOVD). Both MLPA and segregation analysis with short tandem repeat markers elucidated the status of the mother, sister and the younger brother of the proband, who were not carriers of the mutation. This case provides a description of a new pathogenic variant presented as de novo mutation in a DMD patient. Haplotype analysis and complete gene screening may improve genetic counseling in cases of germline mosaicism and de novo mutations.

Duchenne muscular dystrophy in a developing country: challenges in management and genetic counseling.

BACKGROUND AND OBJECTIVE: Multidisciplinary management of Duchenne Muscular Dystrophy (DMD) has achieved outstanding results in developed nations. We aimed to describe the status of diagnosis and management of DMD in a developing country through the experience of non-profit organizations. METHODS: A Multistate, multiple-source, population-based survey was performed from medical records of 432 patients. Data were retrospectively collected, reviewed and curated by health specialists; including clinical features, age at first symptoms, age at diagnosis, disease progression and management, family history, education, age and cause of death. RESULTS: There is a delay in noticing first symptoms and it did not diminish over the past 20 years. Less than 30% of patients obtained definite diagnosis and most of them are in physiotherapy programs but not under steroid treatment. In our study, family history does not anticipate recognition of symptoms compared to sporadic cases (p = 0.05). Approximately 93.33% of our patients attended to education programs. Mean age at death was 18.94 +/- 6.73 years and the most frequent cause was pneumonia. CONCLUSION: Delayed diagnosis of DMD in Mexico is mainly caused by the late detection of first symptoms. There is no difference in early detection of symptoms between familiar and sporadic cases. Lifespan of patients in our cohort is reduced compared to developed countries. The late diagnosis and low percentage of definite cases may affect patient management and genetic counseling and could also preclude participation of patients into novel clinical trials.

Efficacy of conduction hyperthermia in the treatment of non-muscle invasive bladder cancer: A systematic review.

INTRODUCTION: Intravesical treatment for non-muscle invasive bladder cancer (NMIBC) aims to reduce recurrences and stop progression. Hyperthermia-enhanced chemotherapy with devices like COMBAT BRS, Unithermia, and BR-TRG-I is a promising alternative to conventional Bacillus de Calmette Guerin (BCG) therapy. OBJECTIVE: To systematically review the efficacy of hyperthermia generated by conduction devices in the treatment of NMIBC. MATERIAL AND METHODS: The review followed the preferred reporting items for systematic reviews and meta-analyses guidelines. A search was performed in the PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov databases. Two reviewers independently assessed the eligibility of candidate studies and abstracted data from studies that met the inclusion criteria. The primary endpoint was assessment of recurrence. Secondary objectives included evaluation of treatment progression and safety. RESULTS: Thirty studies meeting inclusion criteria underwent data extraction. In intermediate-risk NMIBC patients, COMBAT versus mitomycin C (MMC) in normothermia revealed no superiority in reducing recurrence or progression. High-risk NMIBC patients using COMBAT achieved similar or superior outcomes to BCG. BR-TRG-I demonstrated superior results over normothermia in intermediate- and high-risk NMIBC patients. Unithermia proved less effective than BCG in high-risk NMIBC. Progression outcomes were promising with COMBAT and BR-TRG-I, but comprehensive analysis was limited due to inconsistent assessment across studies. Adverse events were primarily mild-moderate, with some device-specific differences. CONCLUSIONS: Studies on conduction hyperthermia present great variability, which do not allow us to determine the superiority of 1 device over another in terms of recurrence, progression, and/or adverse effects. Further research with consistent administration protocols is crucial for definitive conclusions.

Evolution of Child and Youth Mental Health in the Context of the COVID-19 Pandemic: A Longitudinal Analysis.

BACKGROUND: The COVID-19 pandemic generated uncertainty and disruption among the child and adolescent population. Multiple studies have documented a worsening of mental health following the pandemic. The main objective of this longitudinal study is to analyze the short-, medium-, and long-term evolution of the overall functioning of children and adolescents treated by a child and adolescent mental health team in the context of the COVID-19 pandemic. METHODS: 420 patients aged 3 to 18 were assessed using the Global Assessment of Functioning (GAF) scale at three time points: during the lockdown, three months later, and three years later. Differences based on gender, diagnosis, and time were analyzed. RESULTS: A significant improvement was observed in the short-term (three months) and long-term (three years) compared to the lockdown period. This improvement was maintained in all diagnostic subgroups except for mixed cases (severe mental pathology), which showed the least improvement. No significant differences were found between males and females. CONCLUSIONS: The child and adolescent population showed a greater capacity for adaptation to the lockdown than expected. Family support, decreased stress, and therapeutic intervention appear to have played an important role in improving mental health.

Postoperative agitation or delirium in paediatric patients. What we know and how to avoid it.

Emergence delirium or postoperative agitation is the name given to the state of altered consciousness that occurs after surgery and especially affects pediatric patients. Its incidence is not negligible, reaching 80% of cases in certain studies. It is frequently confused with other clinical entities, for which reason a scale has been validated to facilitate its diagnosis. Risk factors include age under 5 years, the presence of pain after surgery and especially intense preoperative anxiety. Pediatric emergence delirium presents as an adverse event after surgery and influences patient safety by significantly increasing patient comorbidity. It is essential to recognize the entity, as well as its risk factors, in order to apply effective preventive measures to reduce its incidence and intensity when it occurs.

Evaluation of tumour size and rete testis invasion in progression free survival of our patients with stage i testicular seminoma. A retrospective observational study of a reference hospital center and literature review.

INTRODUCTION: The aim of this study was to evaluate the impact of tumour size and rete testis invasion in progression free survival of our patients with stage I testicular seminoma. A literature review is also made. MATERIAL AND METHODS: A retrospective observational study was performed. We included patients with stage I seminoma between January 2010 and July 2022. Patients without factors of poor prognostic -Group A- were compared with patients with factors of poor prognostic -Group B-. Kaplan-Meier curves and log-rank testing were used to compare progression free survival (PFS) between these groups. Statistical significance was considered at P≤.05. RESULTS: 55 patients were included in this study. 20 patients (36.4%) were of good prognostic -Group A- and 35 (63.6%) had factors of poor prognostic -Group B-. The mean age was similar in both groups (mean±standard deviation), 38.62±9.04 years. The mean follow-up time was 63.5±33.6 months. All the patients in group A and 25.7% of the patients in group B underwent active surveillance (AS). 26 patients (74.3%) of the patients in Group B were treated with one cycle of adyuvant carboplatin. Three patients suffered a relapse with retroperitoneal lymph nodes (10.3%), all of them were treated with three cycles of BEP, with a complete response of the disease. No statistical significant differences were found in PFS between Group A and B (log Rank P=.317). CONCLUSION: Individualization of adjuvant treatment in stage I seminoma is important, avoiding the adverse effects derived from them.

Prostate health index (PHI) as an accurate prostate cancer predictor.

PURPOSE: This study aims to compare the ability of the PHI versus tPSA test to predict the presence of PCa in our population. METHODS: A prospective observational study was performed. We included patients with tPSA ≥ 2.5 ng/ml, biopsy naïve or previous negative biopsy, undergoing a blood test, which includes tPSA, fPSA, and p2PSA, and a prostate biopsy between March 2019 and March 2022. Patients with PCa found in the biopsy-Group A-were compared with patients with a negative biopsy result-Group B. Diagnostic accuracy of tPSA and PHI was assessed by receiver operating characteristic [ROC] curves and logistic regression. RESULTS: 140 men were included. Fifty-seven (40.7%) had a positive prostate biopsy result (Group A), and 83 (59.3%) had a negative biopsy result (Group B). The mean age was similar in both groups (mean ± standard deviation), 66.86 ± 6.61 years. No difference was found in the tPSA value between the groups (Group A PSA: 6.11 ng/ml (3.56-17.01); Group B: 6.42 ng/ml (2.46-19.45), p = 0.41). The mean value of PHI was statistically different between groups (Group A 65.50 (29-146) vs. Group B 48 (16-233), p = 0.0001). The area under the curve 0.44 for tPSA and 0.77 for PHI. The multivariate logistic regression model applied to PHI showed a significant increase in its predictive accuracy: 72.14% in the model without PHI, 76.09% with PHI. CONCLUSION: The PHI test improves PCa detection compared to tPSA in our population.

Anaesthetic considerations for elective cesarean section in a patient with a giant Tarlov cyst.

Tarlov cysts are a pathological dilatation of the meninges. Their incidence is more frequent in women between 30 and 50 years of age. The imaging test of choice for diagnosis is MRI. Of unknown etiology, most cases are asymptomatic, but symptoms of radicular irritation, among others, may occur. The therapeutic possibilities are multiple, reserving surgical excision as the last option. We report a case of successful spinal anaesthesia for elective cesarean section in a patient with a giant Tarlov cyst but with potential airway compromise, in whom the risks of general anaesthesia would be increased. Anaesthetic management presents a challenge for the anesthesiologist, especially in situations where the patient presents an increased anaesthetic risk for general anaesthesia, as is the case in the obstetric patient.