Etiological Hypotheses Research Articles

Desentrañando el enigma neurológico: Diabetes insípida central y desmielinización osmótica extrapontina causada por covid-19-reporte de caso

Background: COVID-19 infection produces various symptoms and affects multiple systems, including the endocrine system. Lesions have been documented at the hypothalamic and pituitary axis, hypothetically explained by the presence of angiotensin II receptors in these structures and by direct immune-mediated viral lesions. These manifest with electrolyte and hormonal alterations. Case report: We present the case of a female patient who, after infection by SARS-CoV-2, presented with hypernatremia refractory to conventional management. Her diagnostic study documented hyposthenuria, high serum osmolarity, and low urinary osmolarity. The condition was corrected with desmopressin, leading to a diagnosis of central diabetes insipidus. A brain MRI revealed a lesion in the pituitary gland, confirming the clinical findings. The only etiological hypothesis for this lesion is its association with SARS-CoV-2 infection. Conclusions: Understanding the complications secondary to COVID-19 infection in the endocrine setting is essential for early diagnosis and targeted treatment. This knowledge can significantly improve the quality of life for patients affected by such complications.

Association between pyrrolizidine alkaloids exposure and risk of abnormal serum indices—Insights from a descriptive cross-sectional study in Yunnan Province

The hazard of pyrrolizidine alkaloids (PAs) has been widely reported in animal studies but rarely in population-based research, especially reports about daily exposure. A single-centre descriptive cross-sectional study was conducted on 552 Lahu Autonomous County residents recruited in 2021. Blood PAs exposure biomarker (pyrrole- protein adduct, PPA) and serum biochemical indices were measured. The prevalence of abnormal serum indices and PAs exposure in this region were elucidated using descriptive analyses. 75 % of Lahu Autonomous County participants were exposed to PAs. PAs exposure risk in males was lower than in females (OR=0.357, 95 % CI: 0.222-0.574), and varied with the ethnicity of Lahu Autonomous County. PPA concentration was positively correlated with serum alanine transaminase (ALT) activity (r=0.6263, P < 0.01) and triglyceride level (r=0.2327, P < 0.01); PAs exposure was positively associated with anbormal serum ALT activity (x2=99.629, P < 0.001; OR=1.428, 95 % CI: 1.293–2.319) and hypertriglyceridemia (x2=15.376, P < 0.001; OR=1.629, 95 % CI: 1.229–2.251). These results suggest that PAs exposure might be a risk factor for serum ALT abnormality and hypertriglyceridemia in the local population. This study conducted the first epidemiological study on PAs exposure in China and established the etiological hypotheses for health issues in Lahu Autonomous County.

Diapedesis leading to hematidrosis due to abrupt emotional suffering (Review).

Hematidrosis constitutes a rare imposing phenomenon encountered millennia ago. It involves the plexus of small, mostly superficial arteries, veins and sweat glands of various parts of the human body. Bloody sweat implies skin pathology. It has been connected to psychogenic impairment and lacks a clear etiology. The present study conducted a historical review using the Thesaurus Linguae Graecae®, Gallica-BNF and Google Books databases. The year 1900 was the mark for full-text works to be included. A second review of the modern literature, over the last 20 years, was carried out using the PubMed/MedLine database. In both eras, the terms h[a]emat[h]idrosis, diapedesis, sudor sanguineus, plus various others vocables of Hellenic and Latin origin, were used as key words. Cases of persons suffering hematidrosis during stigmata as partly connected to this study were surveyed and discussed separately. References were obtained from the classical Greece, late Hellenic antiquity and Roman era. A number of 70 cases were registered from the Renaissance to 1900, and 44 cases between 2007 and 2022. The later time interval is considered as the selection of references of all time, while the 1870 to 1884 interval followed. Differences in sex were observed (males, 60.6%; and females, 39.4%; vs. males, 25.6%; and females, 74.4%). The scalp, forehead, face, trunk, arms and legs were the most common areas of appearance in both time intervals. The eyes and ears were the most common areas of appearance in the modern era. As regards the limitations of the present review, it should be emphasized that not all historical cases were available for survey. Stigmata were studied independently. Records in etiology hypothesis, pathological description and the manifestation of a cluster of post-triggering effects described were similar over time. The modern way of life, major stressful events, a fear of death, hematological disorders, vessel derangements and deep faith may trigger hematidrosis. This spectacular acute event stimulates alertness in patients, family, caregivers and physicians, and may lead to social isolation and unnecessary diagnostic and/or therapeutic interventions. The present narrative review aimed to connect science with history and religion, promote contemplation among health professionals and highlight a medical peculiarity. An open mind is warranted in order to comprehend phenomena in religion. Education for the family and a knowledge update for health professionals is also necessary.

Endocrine-disrupting effects of bisphenol-A, thiamethoxam, and fipronil in hormone-naïve transmen compared to cis-women.

Current evidence suggests that the etiology of gender dysphoria (GD) is multifactorial: this, however, remains unclear. Endocrine-disrupting chemicals (EDCs) are one of the etiological hypotheses. In this study, we aimed to evaluate the urinary levels of bisphenol A (BPA), thiamethoxam, and fipronil in hormone-naïve transmen compared with case-matched cis-women as well as the relation between sex hormone levels and EDCs. Drug-naïve transmen diagnosed with GD and who were referred from the psychiatry outpatient clinic to the outpatient clinic of the Department of Endocrinology, Marmara University Hospital, were included in the study. These individuals were assessed for eligibility; 38 drug-naïve transmen and 22 cis-women were recruited as the control group. After anthropometric evaluation laboratory tests for FSH, LH, total testosterone, and estradiol were carried out, spot urine samples were collected to evaluate the urine metabolic excretion of BPA, thiamethoxam, and fipronil. We found that androgens, total testosterone, androstenedione, and DHEAS levels were significantly higher in transmen than in cis-women. Thiamethoxam was considerably higher in cis-women than in transmen, whereas fipronil and BPA levels were similar in both groups. A negative correlation was found between thiamethoxam and testosterone and between thiamethoxam and BPA levels. The available data suggest that the EDCs that we are most exposed to in our lives are not the only factor in GD development. Even transmen who have not taken hormone replacement have high testosterone levels; however, the mechanism has not as yet been elucidated. The challenge is to determine whether this is a factor leading to GD or a condition that develops in common with GD.

Unraveling the Boundaries, Overlaps, and Connections between Schizophrenia and Obsessive-Compulsive Disorder (OCD).

Schizophrenia (SCZ) and obsessive-compulsive disorder (OCD) typically have distinct diagnostic criteria and treatment approaches. SCZ is characterized by delusions, hallucinations, disorganized speech, and cognitive impairments, while OCD involves persistent, intrusive thoughts (obsessions) and repetitive behaviors (compulsions). The co-occurrence of these disorders increases clinical complexity and poses significant challenges for diagnosis and treatment. Epidemiological studies indicate a significant overlap, with prevalence rates of comorbid OCD in SCZ patients ranging from 12% to 25%, which is higher than in the general population. Etiological hypotheses suggest shared genetic, neurobiological, and environmental factors, with genetic studies identifying common loci and pathways, such as glutamatergic and dopaminergic systems. Neuroimaging studies reveal both overlapping and distinct neural abnormalities, indicating shared and unique neurobiological substrates. Environmental factors, like early life stressors and urbanicity, also contribute to the comorbidity. The overlapping clinical features of both disorders complicate diagnosis. Treatment approaches include combining SSRIs with antipsychotics and cognitive behavioral therapy (CBT). The complexity of SCZ and OCD comorbidity underscores the need for a dimensional, spectrum-based perspective on psychiatric disorders, alongside traditional categorical approaches, to improve diagnosis and treatment outcomes.

Is Simpler Always Better? The Case for Going Beyond the Amyloid Hypothesis in Alzheimer's Disease.

Alzheimer's disease (AD) research has been dominated by the single-factor amyloid hypothesis in the last decades. Several other hypotheses have been proposed and increasingly attract attention considering the limited success of amyloid-based therapeutic strategies. Surprisingly, most published alternative etiological hypotheses for AD are similarly single-factor hypotheses, such as vascular, metabolic, mitochondrial, infectious, and inflammatory hypotheses, but the existence of so many different hypotheses suggests that AD is most likely a complex, multifactorial disorder. This inventory of different etiological hypotheses will hopefully help the field to move forward with explanatory models that consider the multifaceted aspects of this devastating disorder.

Late-Onset Reactions after Hyaluronic Acid Dermal Fillers: A Consensus Recommendation on Etiology, Prevention and Management.

Hyaluronic acid (HA) dermal fillers, generally considered low-risk, can lead to rare late-onset reactions (LORs) manifesting between 3 and 4 months postinjection, occasionally even as early as 24h postinjection. The Complication Assessment and Risk Evaluation (CARE) board was established to review these reactions. In this publication, the authors aims to explore the etiological hypotheses underlying LORs, associated risk factors, prevention, and management approaches suggested by the CARE board. The CARE board identified three etiological hypotheses contributing to LORs. Firstly, the physicochemical structure of the filler, particularly low molecular weight HA, which may trigger an immune response. Secondly, infection, potentially introduced during injection or by dormant biofilm activation. Lastly, an imbalance in the host immune system, caused by factors like autoimmune diseases or viral infections, may lead to extended foreign body reactions, delayed type IV hypersensitivity, or adjuvant-based reactions. Based on these hypotheses, the board categorized various risk factors as patient-related (e.g., recent dental treatment, current medical status, active autoimmune disease), product-related (e.g., molecular weight), and procedure-related (e.g., aseptic technique and trauma). To reduce the risk of LORs, the CARE board recommends diligent patient selection, including comprehensive medical history assessment and informed consent. Practitioners should maintain an effective aseptic technique, and choose an appropriate product and injection depth for the anatomical location. Post-procedure, patients should receive education on proper filler care. Management of LORs depends on the suspected etiology, and the CARE board has proposed an algorithm to determine the most appropriate treatment. Hyaluronidase is recommended for noninflammatory reactions in the absence of active infection, while watchful waiting and/or steroid treatment may be preferred for inflammatory reactions. Hyaluronidase is not recommended as a first-line treatment for infections, which require drainage, bacterial culture, and antibiotic treatment. However, the board emphasizes the need for individualized evaluation and treatment in all cases.

Abstract PS13-01: Worse Prognosis for Breast Cancer in the Second and Third Trimesters and Shortly Postpartum:An Update of the Dutch Pregnancy-Associated Breast Cancer Cohort

Abstract Rationale: Pregnancy-Associated Breast Cancer (PABC), often defined as breast cancer during pregnancy (PrBC) or in the first year postpartum (PPBC), is known for its aggressive histopathology and higher stage at diagnosis. In a previous study of the nationwide Dutch PABC Cohort, we observed an impaired survival for patients diagnosed in the second and third trimester of pregnancy. However, the etiology of these differences, and how this relates to the patients diagnosed with breast cancer in the postpartum period (PPBC) or after an abortion (AABC), remains to be elucidated. While we are exploring the etiologic hypotheses, we updated and expanded our database to compare these specific PABC subgroups. Methods: All pathology reports of invasive breast carcinoma between January 1st 1988 and July 1st 2022 were screened for pregnancy-related keywords to find all patients diagnosed with PrBC, PPBC or AABC within one year after childbirth or an interrupted pregnancy (induced abortion or miscarriage before a gestational age of 24 weeks). A local patient series provided 22 additional cases. Pregnant patients were subdivided by gestational trimester at time of diagnosis. The different PrBC, PPBC and AABC subgroups were compared by histopathology, clinical characteristics and outcome. Results: 787 patients were included, of whom 60% were pregnant during their diagnosis. Median age at diagnosis was 34 years. In line with our previous findings, a large majority (68%) of patients had a Bloom &amp; Richardson (B&amp;R) grade III tumor and 37% of tumors were triple negative. Moreover, over a third of patients presented with lymph node metastases (38%). We observed two distinct groups based on histopathology and prognosis: group A, consisting of three patient groups: (I) patients diagnosed in the first trimester of pregnancy, (II) patients diagnosed between 6-12 months postpartum, and (III) patients diagnosed after an abortion, and group B, consisting of two patient groups, (I) patients diagnosed in the second or third trimester of pregnancy or (II) within 6 months after childbirth. Compared to group A, patients in group B more often had B&amp;R grade III tumors: (73% vs. 60%, p=0.002) and more frequently had triple negative tumors (43% vs. 28% in group A, p&amp;lt; 0,001). Survival was significantly worse for patients in group B (5-year OS 67,3% versus 88.2%, p&amp;lt; 0.001). In a multivariable analysis, corrected for grade, type of surgery and overall stage, these differences upheld with an HR of 1.515 (95% CI 1,012 – 2,268). Conclusions: With this extensive update of our nationwide Dutch PABC cohort, we show that especially PrBC patients diagnosed in the second and third trimesters and PPBC patients within six months after childbirth exhibit unfavorable tumor characteristics, with an associated worse prognosis. This highlights the need for in-depth analyses in these specific groups of PABC patients to elucidate the etiologic mechanisms involved. Citation Format: Carsten Bakhuis, Carmen Van Dooijeweert, Britt Suelmann, Janneke Verloop, Pieter Westenend, Sabine Linn, Paul Van Diest, Elsken Van der Wall. Worse Prognosis for Breast Cancer in the Second and Third Trimesters and Shortly Postpartum:An Update of the Dutch Pregnancy-Associated Breast Cancer Cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS13-01.

THERAPEUTIC OPTIONS IN CALCIFIC ROTATOR CUFF TENDINOPATHY OF THE SHOULDER

Calcific tendinopathy in the tendons of the rotator cuff muscles of the shoulder is an increasingly common and disabling pathology. Calcific tendinopathy is a common disease that mainly affects people aged between 40 and 60. Women seem to be more affected than men. It has been suggested that various factors play a role in the condition, such as abnormal thyroid gland activity, metabolic diseases (e.g. gout, diabetes) and genetic predisposition. Various aetiological hypotheses have been put forward: the degenerative and multiphasic theories are the two most widely accepted. Clinically, calcific tendonitis is characterised by severe, disabling pain, often occurring spontaneously, usually in the morning or following exertion disproportionate to subsequent symptoms. There may be concomitant stiffness, giving rise to a clinical picture resembling frozen shoulder or hyperalgesic painful shoulder. Conventional radiography of the shoulder is the most appropriate imaging approach, but perfectly complemented by soft tissue ultrasound. Most acute painful episodes resolve spontaneously symptomatically. Numerous conservative treatments have been reported in the literature with varying levels of evidence of efficacy. In the present study we tried to evaluate which therapeutic option could give superior results both from a functional, lesional architectural and causal point of view in terms of reduction of callus size, but also from an imaging point of view. The use of various therapeutic protocols have shown a significant benefit of the association of ESWT with conventional FKT, and intra-articular infiltration, with a plus for the association of Corticosteroids and Sodium Hyaluronate regarding the speed of achieving the desired results. Similar results were obtained with the intra-articular shoulder PRP technique, but with slower achievement of the desired results. Arthroscopic surgery is the orthopaedic specialist's last option. Keywords: Calcific tendinopathy, rotator cuff muscles, shoulder, intra-articular infiltration.

Depression as reversible biopsychosocial break up after schismogenesis

In recent decades, an important amount of biomedical and psychosocial data regarding major depression etiology and treatment has emerged. Despite this wealth of information, a global hypothesis seeking to integrate all available data into a unified explanatory model of depression is still missing. The biopsychosocial model is a precedent in this endeavor. This model proposes a systemic conceptual framework, suggesting that the dynamic interactions of biological, psychological, and social factors constantly condition individuals’ health status. However, it has been criticized for its lack of practical utility when it comes to understanding the onset and potential reversion of depression. Gregory Bateson proposed a systemic, transdisciplinary construct that may be useful for addressing these criticalities: schismogenesis. While this concept has found increasing application across different areas such as politics, ecology, or even psychotherapy, to the best of our knowledge, its use as a biopsychosocial etiology hypothesis for depression remains unexplored. The schismogenesis hypothesis suggests that depression can be considered as a switching process mediated by positive feedback curves, leading to a functional dissociation due to insufficient inhibitory control. Nonetheless, this process can be either reversed spontaneously or through external help, resulting in a rebalancing of the system.

Do traumatic events and substance use co-occur during adolescence? Testing three causal etiologic hypotheses.

Why do potentially traumatic events (PTEs) and substance use (SU) so commonly co-occur during adolescence? Causal hypotheses developed from the study of posttraumatic stress disorder (PTSD) and substance use disorder (SUD) among adults have not yet been subject to rigorous theoretical analysis or empirical tests among adolescents with the precursors to these disorders: PTEs and SU. Establishing causality demands accounting for various factors (e.g. genetics, parent education, race/ethnicity) that distinguish youth endorsing PTEs and SU from those who do not, a step often overlooked in previous research. We leveraged nationwide data from a sociodemographically diverse sample of youth (N = 11,468) in the Adolescent Brain and Cognitive Development Study. PTEs and substance use prevalence were assessed annually. To account for the many pre-existing differences between youth with and without PTE/SU (i.e. confounding bias) and provide rigorous tests of causal hypotheses, we linked within-person changes in PTEs and SU (alcohol, cannabis, nicotine) across repeated measurements and adjusted for time-varying factors (e.g. age, internalizing symptoms, externalizing symptoms, and friends' use of substances). Before adjusting for confounding using within-person modeling, PTEs and SU exhibited significant concurrent associations (βs = .46-1.26, ps < .05) and PTEs prospectively predicted greater SU (βs = .55-1.43, ps < .05) but not vice versa. After adjustment for confounding, the PTEs exhibited significant concurrent associations for alcohol (βs = .14-.23, ps < .05) and nicotine(βs = .16, ps < .05) but not cannabis (βs = -.01, ps > .05) and PTEs prospectively predicted greater SU (βs = .28-.55, ps > .05) but not vice versa. When tested rigorously in a nationwide sample of adolescents, we find support for a model in which PTEs are followed by SU but not for a model in which SU is followed by PTEs. Explanations for why PTSD and SUD co-occur in adults may need further theoretical analysis and adaptation before extension to adolescents.

Circulating miR-30e-3p induces disruption of neurite development in SH-SY5Y cells by targeting ABI1, a novel biomarker for schizophrenia

Schizophrenia (SCZ) represents a set of enduring mental illnesses whose underlying etiology remains elusive, posing a significant challenge to public health. Previous studies have shown that the neurodevelopmental process involving small molecules such as miRNA and mRNA is one of the etiological hypotheses of SCZ. We identified and verified that miR-30e-3p and ABI1 can be used as biomarkers in peripheral blood transcriptome sequencing data of patients with SCZ, and confirmed the regulatory relationship between them. To further explore their involvement, we employed retinoic acid (RA)-treated SH-SY5Y differentiated cells as a model system. Our findings indicate that in RA-induced SH-SY5Y cells, ABI1 expression is up-regulated, while miR-30e-3p expression is down-regulated. Functionally, both miR-30e-3p down-regulation and ABI1 up-regulation promote apoptosis and inhibit the proliferation of SH-SY5Y cells. Subsequently, the immunofluorescence assay detected the expression location and abundance of the neuron-specific protein β-tubulinIII. The expression levels of neuronal marker genes MAPT, TUBB3 and SYP were detected by RT-qPCR. We observed that these changes of miR-30e-3p and ABI1 inhibit the neurite growth of SH-SY5Y cells. Rescue experiments further support that ABI1 silencing can correct miR-30e-3p down-regulation-induced SH-SY5Y neurodevelopmental defects. Collectively, our results establish that miR-30e-3p′s regulation of neurite development in SH-SY5Y cells is mediated through ABI1, highlighting a potential mechanism in SCZ pathogenesis.

Polyamine Dysregulation and Nucleolar Disruption in Alzheimer's Disease.

A hypothesis of Alzheimer's disease etiology is proposed describing how cellular stress induces excessive polyamine synthesis and recycling which can disrupt nucleoli. Polyamines are essential in nucleolar functions, such as RNA folding and ribonucleoprotein assembly. Changes in the nucleolar pool of anionic RNA and cationic polyamines acting as counterions can cause significant nucleolar dynamics. Polyamine synthesis reduces S-adenosylmethionine which, at low levels, triggers tau phosphorylation. Also, polyamine recycling reduces acetyl-CoA needed for acetylcholine, which is low in Alzheimer's disease. Extraordinary nucleolar expansion and/or contraction can disrupt epigenetic control in peri-nucleolar chromatin, such as chromosome 14 with the presenilin-1 gene; chromosome 21 with the amyloid precursor protein gene; chromosome 17 with the tau gene; chromosome 19 with the APOE4 gene; and the inactive X chromosome (Xi; aka "nucleolar satellite") with normally silent spermine synthase (polyamine synthesis) and spermidine/spermine-N1-acetyltransferase (polyamine recycling) alleles. Chromosomes 17, 19 and the Xi have high concentrations of Alu elements which can be transcribed by RNA polymerase III if positioned nucleosomes are displaced from the Alu elements. A sudden flood of Alu RNA transcripts can competitively bind nucleolin which is usually bound to Alu sequences in structural RNAs that stabilize the nucleolar heterochromatic shell. This Alu competition leads to loss of nucleolar integrity with leaking of nucleolar polyamines that cause aggregation of phosphorylated tau. The hypothesis was developed with key word searches (e.g., PubMed) using relevant terms (e.g., Alzheimer's, lupus, nucleolin) based on a systems biology approach and exploring autoimmune disease tautology, gaining synergistic insights from other diseases.

Recent Advances on Selenium Nutrition and Keshan Disease.

Keshan disease (KD) is a type of endemic cardiomyopathy with an unknown cause. It is primarily found in areas in China with low selenium levels, from northeast to southwest. The nutritional biogeochemical etiology hypothesis suggests that selenium deficiency is a major factor in KD development. Selenium is important in removing free radicals and protecting cells and tissues from peroxide-induced damage. Thus, low environmental selenium may affect the selenium level within the human body, and selenium level differences are commonly observed between healthy people in KD and nonKD areas. From the 1970s to the 1990s, China successfully reduced KD incidence in endemic KD areas through a selenium supplementation program. After years of implementing prevention and control measures, the selenium level of the population in the KD areas has gradually increased, and the prevalence of KD in China has remained low and stable in recent years. Currently, the pathogenesis of KD remains vague, and the effect of selenium supplementation on the prognosis of KD still needs further study. This paper comprehensively reviews selenium deficiency and its connection to KD. Thus, this study aims to offer novel ideas and directions to effectively prevent and treat KD in light of the current situation.

Guillain-Barre syndrome after snakebite: a case report and systematic review

Guillain-Barré Syndrome (GBS) is a polyneuropathy characterized by acute-onset and immune-mediated processes, triggered by various factors. The occurence of GBS in connection with snakebites is rare. In this report, we present a rare clinical case with neuro-muscular and hematological complications following a snakebite, leading to flask quadriplegia on the 14th day during intensive care follow-up. Cerebrospinal fluid (CSF) analysis indicated albumin-cytological dissociation, and Electromyography (EMG) revealed findings consistent with acute motor axonal neuropathy, resulting in a diagnosis of GBS. After undergoing plasmapheresis once, the patient swiftly developed refractory septic shock, leading to a fatal outcome. In this study, we report a GBS case as a conseqeunce of snakebite together with a systematic review of the medical literature on the development of GBS after snakebite. Although current case reports and findings have broadened the scope of etiologic hypotheses for GBS including snake envenomation, further studies are needed to confirm the association between GBS following snakebite.

Exploring Patient Demographics and Presence of Retinal Vascular Disease in Paracentral Acute Middle Maculopathy

PurposeTo investigate the sociodemographic profile, the association with retinal vascular diseases (RVD) and systemic comorbidities, and visual outcomes of patients with paracentral acute middle maculopathy (PAMM) in a large, ethnically diverse single-center cohort. DesignRetrospective cohort study. MethodsElectronic health record query for all patients presenting with PAMM at Moorfields Eye Hospital, London, was completed. Detailed demographics, clinical and systemic information were collected and analyzed. ResultsA total of 78 eyes of 78 patients with confirmed PAMM were included in the study. 40 patients(51.3%) presented with no RVD, 20 patients(25.6%) with retinal vein occlusion(RVO), 16 patients(20.5%) with retinal artery occlusion(RAO), and two patients(2.6%) with concomitant RAO and RVO. Patients with PAMM+RAO were older than those with RVO(p=0.02) and more likely to have a history of major adverse cardiovascular events(MACE)(p=0.01), with a significantly worse presenting best corrected visual acuity (BCVA)(20/50) compared to patients with RVO (p=0.02) and no RVD (p<0.001). Individuals with isolated PAMM had a significantly higher prevalence of previous MACE (p=0.04) and sickle cell disease (SCD) (p=0.04) compared to those with RVO. At the last follow-up, 64 patients (85.3%) had a good BCVA (>20/32). ConclusionsThe significant association of PAMM with RVD supports the hypothesis of an ischemic etiology. Individuals with isolated PAMM had a higher prevalence of MACE and SCD. Thus, it is important to prompt immediate referral for a comprehensive systemic evaluation. Across the whole cohort, PAMM was associated with good BCVA improvement during follow-up, indicating a good visual prognosis.

Altered in vivo early neurogenesis traits in patients with depression: Evidence from neuron-derived extracellular vesicles and electroconvulsive therapy

BackgroundThe neurogenesis hypothesis is a promising candidate etiologic hypothesis for depression, and it is associated with electroconvulsive therapy (ECT). However, human in vivo molecular-level evidence is lacking. ObjectiveWe used neuron-derived extracellular vesicles (NDEVs) as a “window to the neurons” to explore the in vivo neurogenesis status associated with ECT in patients with treatment-resistant depression (TRD). MethodsIn this study, we enrolled 40 patients with TRD and 35 healthy controls (HCs). We isolated NDEVs from the plasma of each participant to test the levels of doublecortin (DCX), a marker of neurogenesis, and cluster of differentiation (CD) 81, a marker of EVs. We also assessed the plasma levels of brain-derived neurotrophic factor (BDNF), a protein that is known to be associated with ECT and neuroplastic processes. ResultsOur findings indicated that both the levels of DCX in NDEVs and BDNF in plasma were significantly lower in TRD patients compared to HCs at baseline, but increased following ECTs. Conversely, levels of CD81 in NDEVs were found higher in TRD patients at baseline, but did not change after the ECT treatments. Exploratory analyses revealed that lower levels of BDNF in plasma and DCX in NDEVs, along with higher CD81 levels in NDEVs, were associated with more severe depressive symptoms and reduced cognitive function at baseline. Furthermore, higher baseline CD81 concentrations in NDEVs were correlated with greater decreases in depression symptoms. ConclusionsWe first present human in vivo evidence of early neurogenesis using DCX through NDEVs: decreased in TRD patients, increased after ECTs.

Meta‐analysis of NIH Alzheimer’s Disease‐Related Dementias (ADRD) programs responsive to the National Plan to Address Alzheimer’s Disease (AD)

AbstractBackgroundAD/ADRD diseases currently impact more than 6 million people in the US. Rare forms of AD/ADRD are caused directly and unambiguously by genetic mutations. However, most AD/ADRD burden is complex in etiology and thought to result from an interplay among multiple incompletely understood genetic, biochemical, lifestyle, environmental and psychosocial risk factors. Moreover, risk factors interact with other health factors to impact AD/ADRD outcomes. For example, while the most common dementia diagnosis is AD, research over the past decade revealed most people with a diagnosis of AD have multiple brain pathologies, other comorbidities, and many people diagnosed with clinical AD do not have AD pathology at all. This new knowledge highlights the importance of better understanding dementia syndromes, and the relationships among them, to increase chances of developing effective interventions. The NINDS partners with the NIA, the NIH lead for AD/ADRD, in the NIH response to the National Plan. NINDS leads ADRD including frontotemporal dementia (FTD), Lewy body dementias (LBD), vascular contributions to cognitive impairment and dementia (VCID) and multiple etiology dementias (MED). This project aims to evaluate NIH and the ADRD field’s responsiveness to ADRD research milestones from triennial NINDS ADRD Summits by mapping NIH‐funded research activities to ADRD milestones.MethodThe approach used text‐based analysis/mining of grant titles, abstracts, and specific aims to map awards and activities to ADRD milestones. Mappings were vetted by expert concurrence. The ongoing study includes new or competitively renewed NIH ADRD awards starting from fiscal year 2017. Findings help NIH to better understand the state of the field, identify research gaps and opportunities for future efforts, and enable public communication of research activities with an accurate, accessible, compact, and updatable data visualizations.ResultResults indicate the approach is feasible, and importantly the field and NIH have largely been responsive to the ADRD milestones in the National Plan to Address AD.ConclusionThe analysis points to several cross‐cutting ADRD research areas that may benefit from increased attention going forward, including health equity, the multiple etiology hypothesis of common dementias, emerging risk factors for common dementias (e.g. COVID‐19, TBI, and TDP‐43 proteinopathy), and clinical trials.

POST-TRAUMATIC STRESS DISORDER IN DOGS UNDER THE CONDITIONS OF MARTIAL STATE

The physical and mental effects of the full-scale war in Ukraine have affected not only people's lives, but also the lives of their pets, who these days are often seen as members of the family. Studies of dog cognition and behavior are recent and have proliferated since the early twenty-first century, when these animals began to be considered "true companions" worthy of study as pets adapted to life in an urbanized environment rather than mere human accessories.&#x0D; Life during a full-scale war, this life is full of stresses, which are primarily constant irritants, namely explosions and sirens. This has a negative impact on the psycho-emotional state of not only people, but also companion animals who may experience post-traumatic stress disorder.&#x0D; Taking into account the relevance of this issue, the article presents a literature review of scientific works related to the topic of post-traumatic stress disorder in dogs against the background of stress due to military operations, namely, the formed etiological hypothesis of the development of the pathology, its prognosis, the clinical features of the manifestations are highlighted in detail. Driving predictors and contributing factors stimulating post-traumatic syndrome have been established. Taking into account the experience of foreign and domestic scientists, a list of drugs that should be used not only for treatment, but also for prevention has been defined.&#x0D; It has been proven that post-traumatic stress disorder often arises as a result of mental destabilization under wartime conditions and can happen to almost every person directly or indirectly involved in the war.

Kidney disease characteristics, prevalence, and risk factors in León, Nicaragua: a population-based study

BackgroundCKD of unknown etiology (CKDu) disproportionately affects young people in Central America who lack traditional CKD risk factors (diabetes and hypertension) and has instead been variably linked to heat stress, occupational and environmental exposures, nephrotoxic medications, and/or genetic susceptibility. This study aimed to estimate the prevalence of CKD and identify risk factors for traditional CKD and CKDu in Nicaragua.MethodsSurveys and assessment for CKD markers in urine and serum were performed in 15–59 year olds in households of the León municipality of Nicaragua. The survey included questions on demographics, health behaviors, occupation, and medical history. Participants with CKD were subdivided into traditional CKD and suspected CKDu based on history of diabetes, hypertension, or other specified conditions. A multinomial logistic regression model was used to identify factors associated with traditional CKD and suspected CKDu, compared to the non-CKD reference group.ResultsIn 1795 study participants, CKD prevalence was 8.6%. Prevalence in males was twofold higher than females (12% vs 6%). Of those with CKD, 35% had suspected CKDu. Both traditional CKD and CKDu were associated with male sex and increasing age. Traditional CKD was associated with a family history of CKD, history of urinary tract infections, and lower socioeconomic status, while CKDu was associated with drinking well water and a lower body mass index.ConclusionsBoth traditional CKD and CKDu are significant burdens in this region. Our study supports previous hypotheses of CKDu etiology and emphasizes the importance of CKD screening.