Prefrontal cortical dynorphin peptidergic transmission constrains threat-driven behavioral and network states.

Prefrontal cortical (PFC) circuits provide top-down control of threat reactivity. This includes ventromedial PFC (vmPFC) circuitry, which plays a role in suppressing fear-related behavioral states. Dynorphin (Dyn) has been implicated in mediating negative affect and maladaptive behaviors induced by severe threats and is expressed in limbic circuits, including the vmPFC. However, there is a critical knowledge gap in our understanding of how vmPFC Dyn-expressing neurons and Dyn transmission detect threats and regulate expression of defensive behaviors. Here, we demonstrate that Dyn cells are broadly activated by threats and release Dyn locally in the vmPFC to limit passive defensive behaviors. We further demonstrate that vmPFC Dyn-mediated signaling promotes a switch of vmPFC networks to a fear-related state. In conclusion, we reveal a previously unknown role of vmPFC Dyn neurons and Dyn neuropeptidergic transmission in suppressing defensive behaviors in response to threats via state-driven changes in vmPFC networks.

Non-binary gender, vulnerable populations and mental health during the COVID-19 pandemic: Data from the COVID-19 MEntal health inTernational for the general population (COMET-G) study.

BACKGROUND: The COVID-19 pandemic has brought significant mental health challenges, particularly for vulnerable populations, including non-binary gender individuals. The COMET international study aimed to investigate specific risk factors for clinical depression or distress during the pandemic, also in these special populations. METHODS: Chi-square tests were used for initial screening to select only those variables which would show an initial significance. Risk Ratios (RR) were calculated, and a Multiple Backward Stepwise Linear Regression Analysis (MBSLRA) was followed with those variables given significant results at screening and with the presence of distress or depression or the lack of both of them. RESULTS: The most important risk factors for depression were female (RR = 1.59-5.49) and non-binary gender (RR = 1.56-7.41), unemployment (RR = 1.41-6.57), not working during lockdowns (RR = 1.43-5.79), bad general health (RR = 2.74-9.98), chronic somatic disorder (RR = 1.22-5.57), history of mental disorders (depression RR = 2.31-9.47; suicide attempt RR = 2.33-9.75; psychosis RR = 2.14-10.08; Bipolar disorder RR = 2.75-12.86), smoking status (RR = 1.15-5.31) and substance use (RR = 1.77-8.01). The risk factors for distress or depression that survived MBSLRA were younger age, being widowed, living alone, bad general health, being a carer, chronic somatic disorder, not working during lockdowns, being single, self-reported history of depression, bipolar disorder, self-harm, suicide attempts and of other mental disorders, smoking, alcohol, and substance use. CONCLUSIONS: Targeted preventive interventions are crucial to safeguard the mental health of vulnerable groups, emphasizing the importance of diverse samples in future research. LIMITATIONS: Online data collection may have resulted in the underrepresentation of certain population groups.

Prefrontal cortical dynorphin peptidergic transmission constrains threat-driven behavioral and network states.

Prefrontal cortical (PFC) circuits provide top-down control of threat reactivity. This includes ventromedial PFC (vmPFC) circuitry, which plays a role in suppressing fear-related behavioral states. Dynorphin (Dyn) has been implicated in mediating negative affect and mal-adaptive behaviors induced by severe threats and is expressed in limbic circuits, including the vmPFC. However, there is a critical knowledge gap in our understanding of how vmPFC Dyn-expressing neurons and Dyn transmission detect threats and regulate expression of defensive behaviors. Here, we demonstrate that Dyn cells are broadly activated by threats and release Dyn locally in the vmPFC to limit passive defensive behaviors. We further demonstrate that vmPFC Dyn-mediated signaling promotes a switch of vmPFC networks to a fear-related state. In conclusion, we reveal a previously unknown role of vmPFC Dyn neurons and Dyn neuropeptidergic transmission in suppressing defensive behaviors in response to threats via state-driven changes in vmPFC networks.

Personal Variables in Attitude toward Green Purchase Intention of Organic Products.

The present research aims to determine whether environmental awareness, green self-identity, and subjective norms influence the attitudes of consumers who identify with environmental issues and have green purchasing intentions for organic products. The research was quantitative, correlational in scope, and cross-sectional in design. It was applied to 710 Peruvian millennials. A questionnaire consisting of 20 questions was applied, which was quantified through a five-point Likert scale. The results were processed through an Exploratory Factor Analysis (EFA), a Confirmatory Factor Analysis (CFA), and Structural Equation Modeling (SEM). Statistical analyses were developed using SPSS 24 and AMOS 24. The study identified that the personal variables influencing the environmental attitudes of millennials who intend to buy green organic products are green self-identity and subjective norms. While environmental awareness does not influence environmental attitudes, it does influence the green self-identity of Peruvian millennials. This study is one of the first to identify the personal variables influencing the environmental attitudes of Peruvian millennials who intend to buy green organic products.

Somatic multicomorbidity and disability in patients with psychiatric disorders in comparison to the general population: a quasi-epidemiological investigation in 54,826 subjects from 40 countries (COMET-G study).

BACKGROUND: The prevalence of medical illnesses is high among patients with psychiatric disorders. The current study aimed to investigate multi-comorbidity in patients with psychiatric disorders in comparison to the general population. Secondary aims were to investigate factors associated with metabolic syndrome and treatment appropriateness of mental disorders. METHODS: The sample included 54,826 subjects (64.73% females; 34.15% males; 1.11% nonbinary gender) from 40 countries (COMET-G study). The analysis was based on the registration of previous history that could serve as a fair approximation for the lifetime prevalence of various medical conditions. RESULTS: About 24.5% reported a history of somatic and 26.14% of mental disorders. Mental disorders were by far the most prevalent group of medical conditions. Comorbidity of any somatic with any mental disorder was reported by 8.21%. One-third to almost two-thirds of somatic patients were also suffering from a mental disorder depending on the severity and multicomorbidity. Bipolar and psychotic patients and to a lesser extent depressives, manifested an earlier (15-20 years) manifestation of somatic multicomorbidity, severe disability, and probably earlier death. The overwhelming majority of patients with mental disorders were not receiving treatment or were being treated in a way that was not recommended. Antipsychotics and antidepressants were not related to the development of metabolic syndrome. CONCLUSIONS: The finding that one-third to almost two-thirds of somatic patients also suffered from a mental disorder strongly suggests that psychiatry is the field with the most trans-specialty and interdisciplinary value and application points to the importance of teaching psychiatry and mental health in medical schools and also to the need for more technocratically oriented training of psychiatric residents.

Multiplex assay for the simultaneous detection of antibodies against small ruminant lentivirus, Mycobacterium avium subsp. paratuberculosis, and Brucella melitensis in goats.

Background and Aim: Brucellosis, paratuberculosis (PTb), and infections caused by small ruminant lentivirus (SRLV), formerly known as caprine arthritis encephalitis virus (CAEV), adversely affect goat production systems. Nonetheless, commonly used diagnostic tests can only determine one analyte at a time, increasing disease surveillance costs, and limiting their routine use. This study aimed to design and validate a multiplex assay for antibody detection against these three diseases simultaneously. Materials and Methods: Two recombinant proteins from the SRLV (p16 and gp38), the native hapten of Brucella melitensis, and the paratuberculosis-protoplasmic antigen 3 from Mycobacterium avium subsp. paratuberculosis (MAP) were used to devise and assess a multiplex assay. Conditions for the Luminex® multiplex test were established and validated by sensitivity, specificity, repeatability, and reproducibility parameters. Cut-off points for each antigen were also established. Results: The 3-plex assay had high sensitivity (84%) and specificity (95%). The maximum coefficients of variation were 23.8% and 20.5% for negative and positive control samples, respectively. The p16 and gp38 SRLV antigens are 97% and 95%, similar to the CAEV sequence found in GenBank, respectively. Conclusion: The multiplex test can be effectively used for the simultaneous detection of antibodies against SRLV, MAP and B. melitensis in goats.

Deficiencia de hierro en enfermedad renal crónica

Contexto: la deficiencia de hierro es un trastorno frecuentemente observado en pacientes con enfermedad renal crónica (ERC), sobre todo en estadios avanzados. Su presencia se asocia a una mayor morbilidad y mortalidad. La deficiencia de hierro puede ser absoluta o funcional. La deficiencia absoluta se refiere a una ausencia o una reducción de las reservas de hierro, mientras que la deficiencia funcional se define por la presencia de depósitos de hierro adecuados pero con una disponibilidad insuficiente de hierro para su incorporación en los precursores eritroides. Varios factores de riesgo contribuyen a la deficiencia absoluta y funcional de hierro en ERC, incluyendo pérdidas hemáticas, absorción alterada de hierro e inflamación crónica. Objetivo: con esta revisión narrativa se pretende presentar las definiciones, los aspectos fisiopatológicos, los criterios diagnósticos y las medidas terapéuticas en el paciente con diagnóstico de ERC con deficiencia de hierro. Metodología: se realizó una revisión no sistemática de la literatura en la base de datos PubMed, incluyendo además las guías internacionales más utilizadas que abordan el tema de deficiencia de hierro en ERC. Resultados: se incluyeron un total de 30 referencias bibliográficas. La deficiencia de hierro puede ser absoluta o relativa y el déficit absoluto de hierro se produce con valores de ferritina 100 mcg/l, pero con una TSAT < 20 %. El tratamiento del déficit absoluto consta de reposición de hierro oral o endovenoso y en pacientes que aún no reciben diálisis, se puede hacer una prueba terapéutica con hierro oral, de no haber respuesta se optará por hierro endovenoso, mientras que en pacientes que sí reciben diálisis, la medida ideal es el hierro endovenoso, preferiblemente en preparaciones que permitan esquemas de altas dosis y bajas frecuencias de administración. Las metas propuestas por las distintas guías presentan variaciones entre 500 y 700 mcg/l de ferritina. Conclusiones: el déficit de hierro debe buscarse activamente en pacientes con ERC, ya que su presencia y la falta de intervención conlleva a un incremento en los desenlaces adversos. La terapia con hierro es el pilar del tratamiento y la elección del agente a utilizar dependerá de las características individuales del paciente y de la disponibilidad de las preparaciones de hierro oral o endovenoso.

Background: Iron deficiency is a disorder frequently observed in patients with chronic kidney disease (CKD), especially in advanced stages. Its presence is associated with increased morbidity and mortality. Iron deficiency can be absolute or functional. Absolute deficiency refers to absent or reduced iron stores, while functional deficiency is defined by the presence of adequate iron stores but insufficient iron availability for incorporation into erythroid precursors. Several risk factors contribute to absolute and functional iron deficiency in CKD, including blood fi, impaired iron absorption, and chronic inflammation. Purpose: With this narrative review, it is intended to present the details, pathophysiological aspects, diagnostic criteria and therapeutic options in patients diagnosed with chronic kidney disease with iron deficiency. Methodology: A non-systematic review of the fi ron ra was carried out, in the PubMed database, also including the most used international guidelines that address the issue fi ron deficiency in chronic kidney disease. Results: A total of 30 bibliographical references were included. Iron deficiency can be absolute or relative. The absolute iron deficiency occurs with ferritin values 100 mcg/l but with a TSAT <20 % Treatment of absolute deficiency consists of oral or intravenous iron replacement. In a patient who is not yet receiving dialysis, a therapeutic trial with oral iron can be done, if there is no response, intravenous iron will be chosen. In patients receiving dialysis, the ideal measure is intravenous iron, preferably in preparations that allow high-dose schemes and low frequencies of administration. The goals proposed by the different guidelines present variations between 500 and 700 mcg/l d ferritin. Conclusions: iron deficiency should be actively sought in patients with CKD, since its presence and lack of intervention leads to an increase in adverse outcomes. Iron therapy is the mainstay of treatment; the choice of the agent to be used depends on the individual characteristics of the patient and the availability of oral or intravenous iron preparations.

Results of the COVID-19 mental health international for the health professionals (COMET-HP) study: depression, suicidal tendencies and conspiracism.

INTRODUCTION: The current study aimed to investigate the rates of anxiety, clinical depression, and suicidality and their changes in health professionals during the COVID-19 outbreak. MATERIALS AND METHODS: The data came from the larger COMET-G study. The study sample includes 12,792 health professionals from 40 countries (62.40% women aged 39.76 ± 11.70; 36.81% men aged 35.91 ± 11.00 and 0.78% non-binary gender aged 35.15 ± 13.03). Distress and clinical depression were identified with the use of a previously developed cut-off and algorithm, respectively. STATISTICAL ANALYSIS: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses, and Factorial Analysis of Variance (ANOVA) tested relations among variables. RESULTS: Clinical depression was detected in 13.16% with male doctors and 'non-binary genders' having the lowest rates (7.89 and 5.88% respectively) and 'non-binary gender' nurses and administrative staff had the highest (37.50%); distress was present in 15.19%. A significant percentage reported a deterioration in mental state, family dynamics, and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (24.64% vs. 9.62%; p < 0.0001). Suicidal tendencies were at least doubled in terms of RASS scores. Approximately one-third of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop clinical depression was associated with a history of Bipolar disorder (RR = 4.23). CONCLUSIONS: The current study reported findings in health care professionals similar in magnitude and quality to those reported earlier in the general population although rates of clinical depression, suicidal tendencies, and adherence to conspiracy theories were much lower. However, the general model of factors interplay seems to be the same and this could be of practical utility since many of these factors are modifiable.

Neuropeptide System Regulation of Prefrontal Cortex Circuitry: Implications for Neuropsychiatric Disorders.

Neuropeptides, a diverse class of signaling molecules in the nervous system, modulate various biological effects including membrane excitability, synaptic transmission and synaptogenesis, gene expression, and glial cell architecture and function. To date, most of what is known about neuropeptide action is limited to subcortical brain structures and tissue outside of the central nervous system. Thus, there is a knowledge gap in our understanding of neuropeptide function within cortical circuits. In this review, we provide a comprehensive overview of various families of neuropeptides and their cognate receptors that are expressed in the prefrontal cortex (PFC). Specifically, we highlight dynorphin, enkephalin, corticotropin-releasing factor, cholecystokinin, somatostatin, neuropeptide Y, and vasoactive intestinal peptide. Further, we review the implication of neuropeptide signaling in prefrontal cortical circuit function and use as potential therapeutic targets. Together, this review summarizes established knowledge and highlights unknowns of neuropeptide modulation of neural function underlying various biological effects while offering insights for future research. An increased emphasis in this area of study is necessary to elucidate basic principles of the diverse signaling molecules used in cortical circuits beyond fast excitatory and inhibitory transmitters as well as consider components of neuropeptide action in the PFC as a potential therapeutic target for neurological disorders. Therefore, this review not only sheds light on the importance of cortical neuropeptide studies, but also provides a comprehensive overview of neuropeptide action in the PFC to serve as a roadmap for future studies in this field.

Biomechanics of the Upper Limbs: A Review in the Sports Combat Ambit Highlighting Wearable Sensors.

Over time, inertial sensors have become an essential ally in the biomechanical field for current researchers. Their miniaturization coupled with their ever-improvement make them ideal for certain applications such as wireless monitoring or measurement of biomechanical variables. Therefore, in this article, a compendium of their use is presented to obtain biomechanical variables such as velocity, acceleration, and power, with a focus on combat sports such as included box, karate, and Taekwondo, among others. A thorough search has been made through a couple of databases, including MDPI, Elsevier, IEEE Publisher, and Taylor & Francis, to highlight some. Research data not older than 20 years have been collected, tabulated, and classified for interpretation. Finally, this work provides a broad view of the use of wearable devices and demonstrates the importance of using inertial sensors to obtain and complement biomechanical measurements on the upper extremities of the human body.

The effect of different degrees of lockdown and self-identified gender on anxiety, depression and suicidality during the COVID-19 pandemic: Data from the international COMET-G study.

INTRODUCTION: During the COVID-19 pandemic various degrees of lockdown were applied by countries around the world. It is considered that such measures have an adverse effect on mental health but the relationship of measure intensity with the mental health effect has not been thoroughly studied. Here we report data from the larger COMET-G study pertaining to this question. MATERIAL AND METHODS: During the COVID-19 pandemic, data were gathered with an online questionnaire from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Anxiety was measured with the STAI, depression with the CES-D and suicidality with the RASS. Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively. STATISTICAL ANALYSIS: It included the calculation of Relative Risk (RR), Factorial ANOVA and Multiple backwards stepwise linear regression analysis RESULTS: Approximately two-thirds were currently living under significant restrictions due to lockdown. For both males and females the risk to develop clinical depression correlated significantly with each and every level of increasing lockdown degree (RR 1.72 and 1.90 respectively). The combined lockdown and psychiatric history increased RR to 6.88 The overall relationship of lockdown with severity of depression, though significant was small. CONCLUSIONS: The current study is the first which reports an almost linear relationship between lockdown degree and effect in mental health. Our findings, support previous suggestions concerning the need for a proactive targeted intervention to protect mental health more specifically in vulnerable groups.

Results of the COVID-19 mental health international for the general population (COMET-G) study.

INTRODUCTION: There are few published empirical data on the effects of COVID-19 on mental health, and until now, there is no large international study. MATERIAL AND METHODS: During the COVID-19 pandemic, an online questionnaire gathered data from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively. STATISTICAL ANALYSIS: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses and Factorial Analysis of Variance (ANOVA) tested relations among variables. RESULTS: Probable depression was detected in 17.80% and distress in 16.71%. A significant percentage reported a deterioration in mental state, family dynamics and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (31.82% vs. 13.07%). At least half of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop depression was associated with history of Bipolar disorder and self-harm/attempts (RR = 5.88). Suicidality was not increased in persons without a history of any mental disorder. Based on these results a model was developed. CONCLUSIONS: The final model revealed multiple vulnerabilities and an interplay leading from simple anxiety to probable depression and suicidality through distress. This could be of practical utility since many of these factors are modifiable. Future research and interventions should specifically focus on them.