Psychogenic non-epileptic seizures (PNES), which closely resemble epileptic seizures (ES), are typically triggered by psychological distress and represent the most prevalent form of conversion disorder encountered in clinical practice. Multiple physical conditions can both precipitate and sustain PNES episodes. Epilepsy, a common neurological disorder, imposes significant emotional and physical burdens, frequently resulting in elevated levels of anxiety and depression. This case report details the clinical course of a 19-year-old female whose PNES was exacerbated by the diagnosis and disease burden of epilepsy. The patient\'s background of childhood trauma, bullying, and sexual abuse likely predisposed her to the development of PNES. Upon receiving a diagnosis of epilepsy, characterized by focal seizures originating from the left parietal region, the patient experienced increased anxiety and required frequent hospitalizations. Despite adjustments to her treatment regimen, including the administration of levetiracetam (LEV) and lacosamide (LCM), her seizures persisted. Comprehensive evaluations, comprising electroencephalography (EEG) and single-photon emission computed tomography (SPECT), indicated the coexistence of epilepsy and PNES. Although surgical intervention was initially considered, it was ultimately deemed unnecessary, which subsequently alleviated the patient\'s anxiety. Psychoeducation highlighting the manageability of her epilepsy with ongoing pharmacotherapy significantly reduced her PNES episodes. This case emphasizes the critical role of addressing the psychosocial burden associated with an epilepsy diagnosis, as these factors may exacerbate PNES. It also underscores the importance of a holistic treatment approach that integrates psychological support with medical management.

Studies have explored the association of particular conditions, or combinations of conditions, and pain among specific populations. However, there is limited information regarding the association of the number of comorbid conditions, as well as other demographic, economic, health, and limitation variables, with pain among adults in the United States. This cross-sectional database study aimed to examine the relationships between number of comorbid conditions (including cancer, arthritis, joint pain, stroke, heart attack, angina, coronary heart disease, high cholesterol, high blood pressure, other heart diseases, diabetes, asthma, chronic bronchitis, and emphysema), demographic, economic, health, and limitation variables with pain among United States adults using 2021 Medical Expenditure Panel Survey data. A multivariable logistic model assessed the association between the number of comorbid conditions (≥6, 5, 4, 3, 2, 1, versus 0 conditions) and quite a bit/extreme (versus little/moderate) pain, adjusting for demographic, economic, health, and limitation variables. The study found that greater numbers of comorbid conditions were associated with higher odds of quite a bit or extreme pain. In addition, age, education, employment, income, overall health, regular physical activity, and three limitation variables were each associated with pain in the multivariable model. These findings offer insight into the association between number of comorbid conditions and other variables with pain and suggest areas where interventions may be helpful to help improve pain outcomes for United States adults.

Real-world data on the range and impact of comorbid health conditions that affect pediatric asthma are scant, especially from developing countries. Lack of data hinders effective diagnosis, treatment, and overall management of these complex cases. We, hereby, describe the common pediatric asthma comorbid conditions in terms of evidence for association, potential mechanisms of impact on asthma control, and treatment benefit. Obesity, upper airway allergies, dysfunctional breathing, multiple sensitizations, depressive disorders, food allergy, and gastro-esophageal reflux are common associations with difficult-to-treat asthma. On the other hand, asthma symptoms and/or management may negatively impact the well-being of children through drug adverse effects, worsening of anaphylaxis symptoms, and disturbing mental health. Awareness of these ailments may be crucial for designing the optimum care for each asthmatic child individually and may ultimately improve the quality of life of patients and their families. A multidisciplinary team of physicians is required to identify and manage such comorbidities aiming to mitigate the over-use of asthma pharmacotherapy. Asthma research should target relevant real-world difficulties encountered at clinical practice and focus on interventions that would mitigate the impact of such comorbidities. Finally, policymakers and global healthcare organizations are urged to recognize pediatric asthma control as a healthcare priority and allocate resources for research and clinical interventions. In other words, global asthma control needs support by compassionate scientific partnership.

BACKGROUND: Human placenta hydrolysates (HPH), the study of which was initiated by the scientific school of Vladimir P. Filatov, are currently being investigated using modern proteomic technologies. HPH is a promising tool for maintaining the function of mitochondria and regenerating tissues and organs with a high content of mitochondria (liver, heart muscle, skeletal muscles, etc.). The molecular mechanisms of action of HPH are practically not studied.
OBJECTIVE: Identification of mitochondrial support mitochondrial function-supporting peptides in HPH (Laennec, produced by Japan Bioproducts).
METHODS: Data on the chemical structure of the peptides were collected through a mass spectrometric experiment. Then, to establish the amino acid sequences of the peptides, de novo peptide sequencing algorithms based on the mathematical theory of topological and metric analysis of chemographs were applied. Bioinformatic analysis of the peptide composition of HPH was carried out using the integral protein annotation method.
RESULTS: The biological functions of 41 peptides in the composition of HPH have been identified and described. Among the target proteins, the activity of which is regulated by the identified peptides and significantly affects the function of mitochondria, are caspases (CASP1, CASP3, CASP4) and other proteins regulating apoptosis (BCL2, CANPL1, PPARA), MAP kinases (MAPK1, MAPK3, MAPK4, MAPK8, MAPK9 , MAPK10, MAPK14), AKT1/GSK3B/MTOR cascade kinases, and a number of other target proteins (ADGRG6 receptor, inhibitor of NF-êB kinase IKKE, pyruvate dehydrogenase 2/3/4, SIRT1 sirtuin deacetylase, ULK1 kinase).
CONCLUSIONS: HPH peptides have been identified that promote inhibition of mitochondrial pore formation, apoptosis, and excessive mitochondrial autophagy under conditions of oxidative/toxic stress, chronic inflammation, and/or hyperinsulinemia.
Актуальность. Гидролизаты плаценты человека (ГПЧ), начало изучения которых было положено научной школой В.П. Филатова, в настоящее время исследуются посредством современных протеомных технологий. ГПЧ представляют собой перспективное средство для поддержания функции митохондрий и регенерации тканей и органов с высоким содержанием митохондрий (печени, сердечной мышцы, скелетной мускулатуры и др.). Молекулярные механизмы действия ГПЧ практически не изучены. Цель. Идентификация в составе ГПЧ (Лаеннек, Japan Bioproducts) пептидов, поддерживающих функционирование митохондрий. Материалы и методы. Данные о химической структуре пептидов собирали посредством масс-спектрометрического эксперимента. Затем для установления аминокислотных последовательностей пептидов применены алгоритмы de novo секвенирования пептидов, основанные на математической теории топологического и метрического анализа хемографов. Биоинформационный анализ пептидного состава ГПЧ осуществлен посредством интегрального метода аннотации белков. Результаты. Идентифицированы и описаны биологические функции 41 пептида в составе ГПЧ. Среди таргетных белков, активность которых регулируется выявленными пептидами и существенно влияет на функцию митохондрий, представлены каспазы (CASP1, CASP3, CASP4) и другие белки регуляции апоптоза (BCL2, CANPL1, PPARA), митоген-активируемые протеинкиназы (MAPK1, MAPK3, MAPK4, MAPK8, MAPK9, MAPK10, MAPK14), киназы каскада AKT1/GSK3B/MTOR и ряд других таргетных белков (рецептор ADGRG6, ингибитор киназы IKKE ядерного фактора каппа-би (NF-êB), пируватдегидрогеназы 2/3/4, НАД-зависимая деацетилаза сиртуин SIRT1, киназа ULK1). Заключение. Установлены пептиды ГПЧ, способствующие торможению формирования митохондриальной поры, апоптоза и избыточной аутофагии митохондрий в условиях оксидативного/токсического стресса, хронического воспаления и/или гиперинсулинемии.

UNASSIGNED: Despite the literature on dydrogesterone, studies on dydrogesterone utilization patterns are largely lacking in Indian patients.
UNASSIGNED: This was a multi-center, retrospective, observational, cross-sectional, and descriptive study across 817 centers in India. Data of patients who received dydrogesterone in past and provided consent for future use of their medical record for research purpose was were retrieved and analyzed.
UNASSIGNED: Data of 7287 subjects (aged 29.55±4.84 years) was analyzed. Threatened abortion was the most common indication for which the subjects received dydrogesterone (46.9%) followed by recurrent pregnancy loss. Polycystic ovary syndrome (PCOS), thyroid disorders and anemia were the most common comorbid conditions and prior pregnancy loss, advanced maternal age and obesity were the most common risk factors seen in subjects who received dydrogesterone. Total 27.5% of subjects received a loading dose of dydrogesterone, and majority (64%) received 40 mg as loading dose. 10 mg dose was used as maintenance or regular dose in 81.4% of the subjects. Twice daily (BID) was the most common dosing frequency (66.6%). The most common concomitant medications being taken by the subjects on dydrogesterone included folic acid (45.1%), iron supplements (30.3%) and calcium and vitamin D3 supplements (25.5%). Another progesterone preparation (oral, injection, vaginal, tubal) other than dydrogesterone was used concurrently in 7.8% of subjects.
UNASSIGNED: The study helped to identify the patient population that is benefitted by dydrogesterone and the preferred indications, risk factors, comorbid conditions and concomitant medication used in this patient population at real-life scenario.

BACKGROUND: Alopecia areata (AA) is an autoimmune condition that causes non-scarring hair loss and can impose a high psychosocial burden on patients. The presence of comorbid conditions may impact the management of AA in clinical practice. This analysis aims to describe disease characteristics and management of AA in patients with concomitant atopic, autoimmune, and psychiatric comorbid conditions.
METHODS: Data were collected from the Adelphi Disease Specific Programme™, a cross-sectional survey of physicians and their adult patients with AA conducted in France, Germany, Italy, Spain, and the UK between October 2021 and June 2022. Patients\' disease severity was based on physician\'s definition. Physician-reported data on demographics, AA clinical characteristics, comorbid conditions, and information related to AA therapies were analyzed. Analyses were descriptive.
RESULTS: Overall, 239 dermatologists provided data for 2083 patients, of which 558 patients (27%) had at least one atopic, autoimmune, or psychiatric comorbid conditions. The most common comorbid conditions were atopic dermatitis, autoimmune thyroid disease, and anxiety. The mean (standard deviation) patient age for the three comorbidity groups was 37.6 years (12.1) and 56% of the patients were women (n = 313). In the three comorbidity groups, 51%, 50%, and 55% of patients with atopic, autoimmune, and psychiatric comorbidities had severe AA with disease progression reported as worsening in 30%, 28%, and 30%, respectively, whereas in the group with no comorbidities, 37% were described as having severe AA and 21% getting worse. Scalp hair loss was the primary sign reported across the three groups of comorbid conditions (atopic, 91%; autoimmune, 91%; psychiatric, 88%). Patients with preselected comorbidities presented more frequently AA-related signs and symptoms beyond scalp hair loss than patients without comorbid conditions. These patients were also more likely to receive topical calcineurin inhibitors, topical immunotherapy, conventional systemic immunosuppressants, and oral Janus kinase inhibitors for the treatment of their AA.
CONCLUSIONS: This analysis provided insights into the burden and management of AA in patients presenting with atopic, autoimmune, and psychiatric comorbid conditions in five European countries.

Critical sized bone defects in the ankle are becoming increasingly more common in patients undergoing limb reconstruction with tibiotalocalcaneal arthrodesis. Bulk allografts have not fared well over time. There have been scattered preliminary reports using custom spinal cages or 3D-printed Titanium Implants to address the critical bony defect; however, the cost of these devices is prohibitive in many clinical practice settings. The purpose of this investigation is to report the preliminary experience using a commercially available Trabecular Metal (Zimmer-Biomet) tibial metaphyseal cone combined with a retrograde locked intramedullary nail to address this challenging problem. Eight consecutive patients underwent tibiotalocalcaneal arthrodesis using a commercially available Trabecular Metal tibial metaphyseal cone combined with a retrograde locked intramedullary nail. Five developed bone loss secondary to neuropathic (Charcot) bony resorption and 3 underwent surgery for failed total ankle arthroplasty. All 8 patients eventually achieved clinical and radiographic healing and were able to ambulate with standard footwear. One patient developed a postoperative wound infection at the site of calcaneal locking screws, which resolved with debridement and parenteral antibiotic therapy. Critical bone defects about the ankle have successfully addressed with custom 3D titanium implants. This small series suggests that similar clinical outcomes can be achieved with the use of a commercially available porous tantalum metaphyseal spacer borrowed from our arthroplasty colleagues, combined with the use of a retrograde locked intramedullary nail.Levels of Evidence: Level 4: Retrospective case series.

The blood-based biomarkers are approaching the clinical practice of Alzheimer\'s disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers.
Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between renal function and blood NfL, P-tau181 was analyzed. An analysis of interactions between various demographic and comorbid factors and eGFR was conducted.
The eGFR levels were negatively associated with plasma concentrations of NfL and P-tau181 (B = - 0.19, 95% CI - 0.224 to - 0.156, P < 0.001; B = - 0.009, 95% CI - 0.013 to -0.005, P < 0.001, respectively). After adjusting for demographic characteristics and comorbid diseases, eGFR remained significantly correlated with plasma NfL (B = - 0.010, 95% CI - 0.133 to - 0.068, P < 0.001), but not with P-tau181 (B = - 0.003, 95% CI - 0.007 to 0.001, P = 0.194). A significant interaction between age and eGFR was found for plasma NfL (Pinteraction < 0.001). In participants ≥ 70 years and with eGFR < 60 ml/min/1.73 m2, the correlation between eGFR and plasma NfL was significantly remarkable (B = - 0.790, 95% CI - 1.026 to - 0,554, P < 0.001).
Considering renal function and age is crucial when interpreting AD biomarkers in the general aging population.

We examined the association between comorbid conditions and mild cognitive impairment (MCI) in Native Hawaiians and Pacific Islanders (NHPI) (n = 54). Cross-sectional, self-reported questionnaires were utilized to collect demographic, comorbid conditions, and MCI (via the AD8 index) data. Separate logistic regression models were conducted to investigate the relationship between comorbid conditions and MCI, adjusting for other covariates. We found significantly increased odds of MCI in those reporting high blood pressure (OR = 5.27; 95% CI: [1.36, 20.46]; p = 0.016), high cholesterol (OR = 7.30; 95% CI: [1.90, 28.14], p = 0.004), and prediabetes or borderline diabetes (OR = 4.53; 95% CI: [1.27, 16.16], p = 0.02) compared with those not reporting these respective conditions. These data show that hypertension, hypercholesterolemia, and prediabetes are associated with MCI in the NHPI community, suggesting that preventive strategies to reduce chronic conditions may also potentially slow cognitive decline in underrepresented/understudied NHPI.

Comorbid conditions represent a major risk for severe illness among persons with COVID-19. Previously healthy people with COVID-19 can also develop severe illness, but are expected to have better outcomes than those with comorbid conditions. Nevertheless, recent data suggest that the former may have, counterintuitively, higher risk of death among those with non-COVID sepsis. However, the epidemiology and outcomes of previously healthy people among critically ill patients with COVID-19 are unknown. We used statewide data to identify intensive care unit (ICU) admissions aged ≥18 years in Texas with COVID-19 in 2020. Multilevel logistic regression was used to estimate the association of comorbid state with short-term mortality (defined as in-hospital mortality or discharge to hospice) overall and with higher illness severity among ICU admissions. Among 52,776 ICU admissions with COVID-19, 6373 (12.1%) were previously healthy. Short-term mortality among previously healthy ICU admissions and those with comorbidities was 16.9% versus 34.6%. On adjusted analyses, the odds of short-term mortality were lower among the previously healthy compared to those with comorbidities overall (adjusted odds ratio (aOR) 0.84 (95% CI: 0.73-0.98)), but did not differ among those with ≥3 organ dysfunctions (aOR 1.11 (95% CI: 0.84-1.46)) and the mechanically ventilated (aOR 0.87 (95% CI: 0.68-1.12)), while being higher among those with do-not-resuscitate status (aOR 1.40 (95% CI: 1.04-1.89)). Over one in eight ICU admissions with COVID-19 were previously healthy. Although being previously healthy was associated with lower risk of death compared to those with comorbidities overall, it had no prognostic advantage among the more severely ill.