Evaluation of force pain thresholds to ensure collision safety in worker-robot collaborative operations.

With the growing demand for robots in the industrial field, robot-related technologies with various functions have been introduced. One notable development is the implementation of robots that operate in collaboration with human workers to share tasks, without the need of any physical barriers such as safety fences. The realization of such collaborative operations in practice necessitates the assurance of safety if humans and robots collide. Thus, it is important to establish criteria for such collision scenarios to ensure robot safety and prevent injuries. Collision safety must be ensured in both pinching (quasi-static contact) and impact (transient contact) situations. To this end, we measured the force pain thresholds associated with impacts and evaluated the biomechanical limitations. This measurements were obtained through clinical trials involving physical collisions between human subjects and a device designed for generating impacts, and the force pain thresholds associated with transient collisions between humans and robots were analyzed. Specifically, the force pain threshold was measured at two different locations on the bodies of 37 adults aged 19-32 years, using two impactors with different shapes. The force pain threshold was compared with the results of other relevant studies. The results can help identify biomechanical limitations in a precise and reliable manner to ensure the safety of robots in collaborative applications.

Ameliorating effect of 2'-fucosyllactose and 6'-sialyllactose on lipopolysaccharide-induced intestinal inflammation.

Human milk oligosaccharides (HMO) affect gut microbiota during neonatal development, particularly with respect to the immune system. Bovine milk-based infant formulas have low oligosaccharide contents. Thus, efforts to fortify infant formulas with HMO are being undertaken. Two major HMO, 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL), exert anti-inflammatory effects; however, the associations between anti-inflammatory effects induced by 2'-FL and 6'-SL cotreatment and gut microbiota composition and metabolite modulation remain unclear. Therefore, in this study, we evaluated the effects of a mixture of these HMO. To determine the optimal HMO ratio for anti-inflammatory effects and elucidate its mode of action, LPS-induced inflammatory HT-29 epithelial cells and intestinal-inflamed suckling mice were treated with various mixtures of 2'-FL and 6'-SL. A 2'-FL:6'-SL ratio of 5:1 was identified as the most effective pretreatment HMO mixture in vitro; thus, this ratio was selected and used for low-, middle-, and high-dose treatments for subsequent in vivo studies. In vivo, high-dose HMO treatment restored LPS-induced inflammation symptoms, such as BW loss, colon length reduction, histological structural damage, and intestinal gene expression related to inflammatory responses. High-dose HMO was the only treatment that modulated the major phyla Bacteroidetes and Firmicutes and the genera Ihubacter, Mageeibacillus, and Saccharofermentans. These changes in microbial composition were correlated with intestinal inflammation-related gene expression and short-chain fatty acid production. To our knowledge, our study is the first to report the effects of Ihubacter, Mageeibacillus, and Saccharofermentans on short-chain fatty acid levels, which can subsequently affect inflammatory cytokine and tight junction protein levels. Conclusively, the HMO mixture exerted anti-inflammatory effects through changes in microbiota and metabolite production. These findings suggest that supplementation of infant formula with HMO may benefit formula-fed infants by forming unique microbiota contributing to neonatal development.

Detection of novel drug-adverse drug reaction signals in rheumatoid arthritis and ankylosing spondylitis: analysis of Korean real-world biologics registry data.

This study aimed to detect signals of adverse drug reactions (ADRs) associated with biological disease-modifying antirheumatic drugs (DMARDs) and targeted therapies in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients. Utilizing the KOrean College of Rheumatology BIOlogics & Targeted Therapy Registry (KOBIO) data, we calculated relative risks, excluded previously reported drug-ADR pairs, and externally validated remaining pairs using US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and single centre's electronic health records (EHR) data. Analyzing data from 2279 RA and 1940 AS patients, we identified 35 significant drug-ADR pairs in RA and 26 in AS, previously unreported in drug labels. Among the novel drug-ADR pairs from KOBIO, 15 were also significant in the FAERS data. Additionally, 2 significant drug-laboratory abnormality pairs were found in RA using CDM MetaLAB analysis. Our findings contribute to the identification of 14 novel drug-ADR signals, expanding our understanding of potential adverse effects related to biological DMARDs and targeted therapies in RA and AS. These results emphasize the importance of ongoing pharmacovigilance for patient safety and optimal therapeutic interventions.

Time to Continuous Renal Replacement Therapy Initiation and 90-Day Major Adverse Kidney Events in Children and Young Adults.

Importance: In clinical trials, the early or accelerated continuous renal replacement therapy (CRRT) initiation strategy among adults with acute kidney injury or volume overload has not demonstrated a survival benefit. Whether the timing of initiation of CRRT is associated with outcomes among children and young adults is unknown. Objective: To determine whether timing of CRRT initiation, with and without consideration of volume overload (VO; <10% vs ≥10%), is associated with major adverse kidney events at 90 days (MAKE-90). Design, Setting, and Participants: This multinational retrospective cohort study was conducted using data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease (WE-ROCK) registry from 2015 to 2021. Participants included children and young adults (birth to 25 years) receiving CRRT for acute kidney injury or VO at 32 centers across 7 countries. Statistical analysis was performed from February to July 2023. Exposure: The primary exposure was time to CRRT initiation from intensive care unit admission. Main Outcomes and measures: The primary outcome was MAKE-90 (death, dialysis dependence, or persistent kidney dysfunction [>25% decline in estimated glomerular filtration rate from baseline]). Results: Data from 996 patients were entered into the registry. After exclusions (n = 27), 969 patients (440 [45.4%] female; 16 (1.9%) American Indian or Alaska Native, 40 (4.7%) Asian or Pacific Islander, 127 (14.9%) Black, 652 (76.4%) White, 18 (2.1%) more than 1 race; median [IQR] patient age, 8.8 [1.7-15.0] years) with data for the primary outcome (MAKE-90) were included. Median (IQR) time to CRRT initiation was 2 (1-6) days. MAKE-90 occurred in 630 patients (65.0%), of which 368 (58.4%) died. Among the 601 patients who survived, 262 (43.6%) had persistent kidney dysfunction. Of patients with persistent dysfunction, 91 (34.7%) were dependent on dialysis. Time to CRRT initiation was approximately 1 day longer among those with MAKE-90 (median [IQR], 3 [1-8] days vs 2 [1-4] days; P = .002). In the generalized propensity score-weighted regression, there were approximately 3% higher odds of MAKE-90 for each 1-day delay in CRRT initiation (odds ratio, 1.03 [95% CI, 1.02-1.04]). Conclusions and Relevance: In this cohort study of children and young adults receiving CRRT, longer time to CRRT initiation was associated with greater risk of MAKE-90 outcomes, in particular, mortality. These findings suggest that prospective multicenter studies are needed to further delineate the appropriate time to initiate CRRT and the interaction between CRRT initiation timing and VO to continue to improve survival and reduce morbidity in this population.

Phase I dose escalation and expansion study of golidocitinib, a highly selective JAK1 inhibitor, in relapsed or refractory peripheral T-cell lymphomas.

BACKGROUND: Relapsed or refractory peripheral T-cell lymphomas (r/r PTCLs) are a group of rare and aggressive diseases that lack effective therapies. Constitutive activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is reported to be associated with PTCLs. Golidocitinib is an oral, potent JAK1 selective inhibitor evaluated in a phase I/II multinational study in patients with r/r PTCLs. PATIENTS AND METHODS: Patients with r/r PTCLs were eligible. The primary objectives were to assess safety and tolerability of golidocitinib and to define its recommended phase II dose (RP2D). The secondary objectives were to evaluate its antitumor activity and pharmacokinetics (PK). RESULTS: A total of 51 patients were enrolled and received golidocitinib treatment at 150 or 250 mg once daily (QD). The median prior lines of therapies were 2 (range: 1-8). Golidocitinib was tolerated at both doses tested, while a higher incidence of serious adverse events and dose modifications at 250 mg were observed. The most common grade ≥3 drug-related treatment-emergent adverse events were neutropenia (27.5%) and thrombocytopenia (11.8%). An objective response rate of 39.2% and a complete response rate of 21.6% were observed. With median follow-up time of 14.7 and 15.9 months, the median duration of response (DoR) and progression-free survival were 8.0 and 3.3 months, respectively. Based on these data, 150 mg QD was defined as the RP2D. Golidocitinib demonstrated a favorable PK profile as an oral agent. Biomarker analysis suggested a potential correlation between JAK/STAT pathway aberrations and clinical activity of golidocitinib. CONCLUSIONS: In this phase I study, golidocitinib demonstrated an acceptable safety profile and encouraging antitumor efficacy in heavily pretreated patients with r/r PTCLs. These results support the initiation of the multinational pivotal study in patients with r/r PTCLs.

Oligodendrocyte precursor cells stop sensory axons regenerating into the spinal cord.

Primary somatosensory axons stop regenerating as they re-enter the spinal cord, resulting in incurable sensory loss. What arrests them has remained unclear. We previously showed that axons stop by forming synaptic contacts with unknown non-neuronal cells. Here, we identified these cells in adult mice as oligodendrocyte precursor cells (OPCs). We also found that only a few axons stop regenerating by forming dystrophic endings, exclusively at the CNS:peripheral nervous system (PNS) borderline where OPCs are absent. Most axons stop in contact with a dense network of OPC processes. Live imaging, immuno-electron microscopy (immuno-EM), and OPC-dorsal root ganglia (DRG) co-culture additionally suggest that axons are rapidly immobilized by forming synapses with OPCs. Genetic OPC ablation enables many axons to continue regenerating deep into the spinal cord. We propose that sensory axons stop regenerating by encountering OPCs that induce presynaptic differentiation. Our findings identify OPCs as a major regenerative barrier that prevents intraspinal restoration of sensory circuits following spinal root injury.

Excitation of NH Stretching Modes in Aromatic Molecules: o-Toluidine and α-Methylbenzylamine.

Selectively excited o-toluidine and α-methylbenzylamine have been studied with quasi-classical trajectory procedures to determine the extent and timescales of intramolecular energy flow. The initial excitation is in the stretching mode of the para-CH bond, and its flow is initiated by interaction with an argon atom. Energy flow to the NH stretching mode is the dominant relaxation pathway, and its effectiveness is enhanced strongly by the methyl-NH interaction. Energy flow characteristics in both molecules are similar, but the flow is more effective in o-toluidine than in α-methylbenzylamine because the methyl group bonded to the benzene ring exerts stronger perturbation on the energy-flow pathway than the group bonded to the side chain. The relaxation of the initially excited CH completes on a timescale of several picoseconds, but the main part of energy flow to the NH occurs on a subpicosecond scale. In o-toluidine, carbon-carbon overtone modes lead to ring-CC bonds gaining and transporting more energy than high-frequency CH bonds, but they all gain far less energy than the NH stretching mode.

Clashes and crowds: protests, riots, and other mass gathering events in North America 2021-2022.

OBJECTIVE: This study aimed to provide an overview of the scope and challenges of historic events and help better prepare emergency healthcare services for future similar mass gathering events. STUDY DESIGN: This was a retrospective descriptive analysis of protest and conflict events in North America from 2021 to 2022. INTRODUCTION: Recent protests, riots, and other conflict events in North America have highlighted the increasing challenges hospital-based and prehospital healthcare providers face. This study provides a retrospective descriptive analysis of protest and conflict events in North America from 2021 to 2022, which may aid emergency healthcare services in understanding the scope and challenges of historic events and help better prepare for future similar mass gathering events. METHODS: Data collection was performed using a retrospective database search through the Armed Conflict Location & Event Data Project (ACLED) database. The ACLED database was searched using the internal database search functions for recorded events that occurred in North America from January 1, 2021 to December 31, 2022. Date, event type, event subtype, the country of incident, and fatality numbers were extracted. The results were exported into an Excel spreadsheet and analyzed independently by L.C., H.S., and R.H. RESULTS: There were a total of 52,529 recorded events of political conflict in North America, with 30,269 events in 2021 and 29,260 in 2022. Political conflict events included protests (40,934, 68.8%), violence against civilians (11,532, 19.4%), strategic developments (2,819, 4.7%), battles (2,293, 3.9%), riots (1,909, 3.2%), and remote violence (42, 0.1%). Violence against civilians caused the highest fatalities (13,466, 82.6%), followed by battles (2,662, 16.3%), riots (111, 0.7%), strategic developments, remote violence, and protests (57, 6, and 3 respectively). CONCLUSION: Mexico and the United States accounted for most of the political conflicts in North America across 2021 and 2022. In Mexico, protests and violence against civilians were the most common types of conflict, with the latter accounting for the comparatively high fatality compared with the other countries. Battles in Mexico between cartels were the most deadly political conflicts recorded in North America.

Persistent Increase in Serum Ferritin Levels despite Converting to Permanent Vascular Access in Pediatric Hemodialysis Patients: Pediatric Nephrology Research Consortium Study.

Our objective was to examine serum ferritin trends after conversion to permanent vascular access (PVA) among children who started hemodialysis (HD) using tunneled cuffed catheters (TCC). Retrospective chart reviews were completed on 98 subjects from 20 pediatric HD centers. Serum ferritin levels were collected at the creation of PVA and for two years thereafter. There were 11 (11%) arteriovenous grafts (AVG) and 87 (89%) arteriovenous fistulae (AVF). Their mean TCC use was 10.4 ± 17.3 months. Serum ferritin at PVA creation was elevated at 562.64 ± 492.34 ng/mL, increased to 753.84 ± 561.54 ng/mL (p = < 0.001) in the first year and remained at 759.60 ± 528.11 ng/mL in the second year (p = 0.004). The serum ferritin levels did not show a statistically significant linear association with respective serum hematocrit values. In a multiple linear regression model, there were three predictors of serum ferritin during the first year of follow-up: steroid-resistant nephrotic syndrome as primary etiology (p = 0.035), being from a center that enrolled >10 cases (p = 0.049) and baseline serum ferritin level (p = 0.017). Increasing serum ferritin after conversion to PVA is concerning. This increase is not associated with serum hematocrit trends. Future studies should investigate the correlation of serum transferrin saturation and ferritin levels in pediatric HD patients.

Efficacy of HER2-Targeted Intraperitoneal 225Ac α-Pretargeted Radioimmunotherapy for Small-Volume Ovarian Peritoneal Carcinomatosis.

Epithelial ovarian cancer (EOC) is often asymptomatic and presents clinically in an advanced stage as widespread peritoneal microscopic disease that is generally considered to be surgically incurable. Targeted α-therapy with the α-particle-emitting radionuclide 225Ac (half-life, 9.92 d) is a high-linear-energy-transfer treatment approach effective for small-volume disease and even single cells. Here, we report the use of human epidermal growth factor receptor 2 (HER2) 225Ac-pretargeted radioimmunotherapy (PRIT) to treat a mouse model of human EOC SKOV3 xenografts growing as peritoneal carcinomatosis (PC). Methods: On day 0, 105 SKOV3 cells transduced with a luciferase reporter gene were implanted intraperitoneally in nude mice, and tumor engraftment was verified by bioluminescent imaging (BLI). On day 15, treatment was started using 1 or 2 cycles of 3-step anti-HER2 225Ac-PRIT (37 kBq/cycle as 225Ac-Proteus DOTA), separated by a 1-wk interval. Efficacy and toxicity were monitored for up to 154 d. Results: Untreated PC-tumor-bearing nude mice showed a median survival of 112 d. We used 2 independent measures of response to evaluate the efficacy of 225Ac-PRIT. First, a greater proportion of the treated mice (9/10 1-cycle and 8/10 2-cycle; total, 17/20; 85%) survived long-term compared with controls (9/27, 33%), and significantly prolonged survival was documented (log-rank [Mantel-Cox] P = 0.0042). Second, using BLI, a significant difference in the integrated BLI signal area to 98 d was noted between controls and treated groups (P = 0.0354). Of a total of 8 mice from the 2-cycle treatment group (74 kBq total) that were evaluated by necropsy, kidney radiotoxicity was mild and did not manifest itself clinically (normal serum blood urea nitrogen and creatinine). Dosimetry estimates (relative biological effectiveness-weighted dose, where relative biological effectiveness = 5) per 37 kBq administered for tumors and kidneys were 56.9 and 16.1 Gy, respectively. One-cycle and 2-cycle treatments were equally effective. With immunohistology, mild tubular changes attributable to α-toxicity were observed in both therapeutic groups. Conclusion: Treatment of EOC PC-tumor-bearing mice with anti-HER2 225Ac-PRIT resulted in histologic cures and prolonged survival with minimal toxicity. Targeted α-therapy using the anti-HER2 225Ac-PRIT system is a potential treatment for otherwise incurable EOC.

Reliability of synthetic diffusion-weighted imaging with a high b-value for paediatric abdominal MRI.

AIM: To evaluate the reliability of synthetic diffusion-weighted imaging (DWI) using a high b-value in comparison to conventional DWI for paediatric abdominal MRI. MATERIALS AND METHODS: Paediatric patients (<19 years old) who underwent liver or pancreatobiliary MRI with DWI using 10 b-values (b = 0, 25, 50, 75, 100, 200, 400, 600, 800, 1,500 s/mm2) from March to October 2021 were included in this retrospective study. Using the software, synthetic DWI using b = 1,500 s/mm2 was generated automatically by selecting the b-value required as output. Conventional and synthetic DWI values for b = 1,500 s/mm2 were measured at the liver, spleen, paraspinal muscle, and mass lesions, if present, and apparent diffusion coefficient (ADC) values were calculated using the mono-exponential model. Intraclass correlation coefficients (ICCs) were calculated to assess the reliability of conventional and synthetic DWI and ADC values with b = 1,500 s/mm2. RESULTS: Thirty paediatric patients (M:F = 22:8, mean 10.8 ± 3.1 years old) were included and four had tumours on abdominal MRI. ICC values were 0.906-0.995 between conventional and synthetic DWI and ADC with b = 1,500 s/mm2 in the liver, spleen and muscle. For mass lesions, ICC values were 0.997-0.999 for both synthetic DWI and ADC images. CONCLUSIONS: Synthetic DWI and ADC values obtained using a high b-value showed excellent agreement with conventional DWI for the liver, spleen, muscle, and mass in paediatric MRI.

17-year trends of body mass index, overweight, and obesity among adolescents from 2005 to 2021, including the COVID-19 pandemic: a Korean national representative study.

OBJECTIVE: There is a lack of pediatric studies that have analyzed trends in mean body mass index (BMI) and the prevalence of obesity and overweight over a period that includes the mid-stage of the COVID-19 pandemic. Thus, we aimed to investigate trends in BMI, overweight, and obesity among Korean adolescents from 2005 to 2021, including the COVID-19 pandemic. SUBJECTS AND METHODS: We used data from the Korea Youth Risk Behavior Web-based Survey (KYRBS), which is nationally representative of South Korea. The study included middle- and high-school students between the ages of 12 and 18. We examined trends in mean BMI and prevalence of obesity and/or overweight during the COVID-19 pandemic and compared these to those of pre-pandemic trends in each subgroup by gender, grade, and residential region. RESULTS: Data from 1,111,300 adolescents (mean age: 15.04 years) were analyzed. The estimated weighted mean BMI was 20.48 kg/m2 (95% CI, 20.46-20.51) between 2005 and 2007, and this was 21.61 kg/m2 (95% CI, 21.54-21.68) in 2021. The prevalence of overweight and obesity was 13.1% (95% CI, 12.9-13.3%) between 2005 and 2007 and 23.4% (95% CI, 22.8-24.0%) in 2021. The mean BMI and prevalence of obesity and overweight have gradually increased over the past 17 years; however, the extent of change in mean BMI and in the prevalence of obesity and overweight during the pandemic was distinctly less than before. The 17-year trends in the mean BMI, obesity, and overweight exhibited a considerable rise from 2005 to 2021; however, the slope during the COVID-19 pandemic (2020-2021) was significantly less prominent than in the pre-pandemic (2005-2019). CONCLUSIONS: These findings enable us to comprehend long-term trends in the mean BMI of Korean adolescents and further emphasize the need for practical prevention measures against youth obesity and overweight.

Rotational thromboelastometry during Cesarean section as a predictive evaluation for the progression of persistent postpartum hemorrhage in parturients with placenta previa: A prospective observational study.

Background: The rotational thromboelastogram (ROTEM) has been used in the management of massive bleeding and transfusion strategy. This study investigated ROTEM parameters measured during Cesarean section as predictors for the progression of persistent postpartum hemorrhage (PPH) in parturients with placenta previa. Methods: This prospective observational study recruited 100 women scheduled for elective Cesarean section after being diagnosed with placenta previa. Recruited women were divided into two groups according to the amount of estimated blood loss: the PPH group (PPH > 1500 ml) vs. the non-PPH group. ROTEM with laboratory tests was performed three times, preoperative, intraoperative, and postoperative time, which were compared between the two groups. Results: The PPH and non-PPH groups included 57 and 41 women, respectively. The area under the receiver-operating characteristic curve of postoperative FIBTEM A5 to detect PPH was 0.76 (95% CI = 0.64 to 0.87; P < 0.001). When postoperative FIBTEM A5 was 9.5, the sensitivity and specificity were 0.74 (95% CI = 0.55 to 0.88) and 0.73 (95% CI = 0.57 to 0.86), respectively. When subgrouping the PPH group based on the postoperative FIBTEM A5 value of 9.5, intraoperative cEBL was similar between the two subgroups; however, postoperative RBC was transfused more in the subgroup with FIBTEM A5 < 9.5 than the subgroup with FIBTEM A5 ≥ 9.5 (7.4 ± 3.0 vs 5.1 ± 2.3 units, respectively; P = 0.003). Conclusion: Postoperative FIBTEM A5, with appropriate selection of the cut-off value, can be a biomarker for more prolonged PPH and massive transfusion following Cesarean section by placenta previa.

Changes of antioxidant enzymes in the kidney after cardiac arrest in the rat model.

Globally, cardiac arrest (CA) is a leading cause of death and disability. Asphyxial CA (ACA)-induced kidney damage is a crucial factor in reducing the survival rate. The purpose of this study was to investigate the role of antioxidant enzymes in histopathological renal damage in an ACA rat model at different time points. A total of 88 rats were divided into five groups and exposed to ACA except for the sham group. To evaluate glomerular function and oxidative stress, serum levels of blood urea nitrogen (BUN) and creatinine (Crtn) and malondialdehyde (MDA) levels in renal tissues were measured. To determine histopathological damage, hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson's trichrome staining were performed. Expression levels of antioxidant enzymes including superoxide dismutase-1 (SOD-1), superoxide dismutase-2 (SOD-2), catalase (CAT), and glutathione peroxidase (GPx) were measured by immunohistochemistry (IHC). Survival rate of the experimental rats was reduced to 80% at 6 h, 55% at 12 h, 42.9% at 1 day, and 33% at 2 days after return of spontaneous circulation. Levels of BUN, Crtn, and MDA started to increase significantly in the early period of CA induction. Renal histopathological damage increased markedly from 6 h until two days post-CA. Additionally, expression levels of antioxidant enzymes were significantly decreased at 6 h, 12 h, 1 day, and 2 days after CA. CA-induced oxidative stress and decreased levels of antioxidant enzymes (SOD-1, SOD-2, CAT, GPx) from 6 h to two days could be possible mediators of severe renal tissue damage and increased mortality rate.

Influence of a Methyl Group on the Unidirectional Flow of Vibrational Energy in an Adenine-Thymine Base Pair.

The role of a methyl group in intramolecular vibrational energy redistribution (IVR) of the hydrogen-bonded adenine-thymine base pair has been studied using classical dynamics procedures. Energy transferred to the doorway bond thymine-NH from the vibrationally excited H2O(v) efficiently redistributes among various bonds of the base pair through vibration-to-vibration coupling, depositing a large fraction of the available energy in the terminal bond adenine-NH. On the other hand, the extent of energy flow in the reverse direction from the excited adenine-NH to thymine-NH is insignificant, indicating IVR in adenine-thymine resulting from the intermolecular interaction with a vibrationally excited H2O molecule, is direction-specific. The unidirectional flow is due to the coupling of stretch-torsion vibrations of a methyl group with conjugated bonds on the thymine ring, when the methyl rotor is present and is adjacent to the vibrationally excited thymine-NH. The insignificance of energy flow from the terminal-to-terminal bond in the reverse direction is attributed to the absence of a methyl group on the adenine moiety, even though the molecule has many CC and CN bonds coupled to their neighbors.

Pharmacology and Ethnomedicinal Potential of Selected Plants Species from Apiaceae (Umbelliferae).

BACKGROUND: The Apiaceae or Umbelliferae is one of the largest families in terms of species representation in the plant kingdom. It is also a prominent family in the field of phytochemicals and pharmacology. The family is also quite prominent in the production of spices and condiments and food supplements in nutrition, aside from the potential of species in the family to induce apoptotic, antimicrobial, antitumor, and hepatoprotective activities. OBJECTIVE: This work presents a detailed structural elucidation and functional aspects of phytochemicals from the Apiaceae or Umbelliferae family. METHODS: Furthermore, the application of members of this family in traditional and modern pharmacology is emphasized. This review also highlights the linkage of phytochemicals used in the conventional system of medication for the development of novel therapeutics through a chain of pre-clinical and clinical trials. CONCLUSION: This study may represent a valuable step ahead in the clinical development of natural drugs for curing several ailments, including respiratory and virus-related diseases.

Finger injuries by eyebrow razor blades in infants.

Infants are occasionally injured while playing with their mother's eyebrow razor, and we have treated several infants with flexor tendon injuries, which in some cases were accompanied by damage to the corresponding digital nerves and/or vessels. Here, we report the outcomes in a retrospective case series, with a review of literature. Between January 2013 and October 2019, 8 patients who met our inclusion criteria were initially investigated. The inclusion criteria were: (1) injured by an eyebrow razor during fiddling or grasping, and (2) the availability of complete medical records and radiological data, with follow-up of at least 2 years. The core sutures were performed using a modified Becker (4-strand) method for flexor digitorum profundus (FDP). Nerves and/or vessels were repaired under microscopy. A long-arm mitten cast was then applied, with the fingers slightly flexed in a resting position, for 3 weeks. Then, the children were allowed to return to unrestricted activity. Formal outpatient hand therapy was not performed. Mean postnatal age was 6.3 months. The FDP was injured in zones 1 and 2 in 3 and 5 infants, respectively. Most of the infants were injured near a dressing table, in the bedroom used by their mother. The colors of these razors were all bright, except for one achromatic (white) razor. All of the razors had been left uncovered, without their cap, or were left open in the case of hinged razors. At a mean follow-up of 35.8 months, range of motion was evaluated by the Strickland and modified Strickland methods; all results were "excellent". We encountered no significant complications in any digit: neuroma, tendon retear, stiffness or necrosis. Uncapped or unfolded colorful eyebrow razors pose a high risk of tendon section with concurrent neurovascular injury in infants. Although satisfactory outcomes can be expected, it seems important to prevent the injury through fastidious parental care and changing razor design and color. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Changes of antioxidant enzymes in the kidney after cardiac arrest in the rat model

Globally, cardiac arrest (CA) is a leading cause of death and disability. Asphyxial CA (ACA)-induced kidney damage is a crucial factor in reducing the survival rate. The purpose of this study was to investigate the role of antioxidant enzymes in histopathological renal damage in an ACA rat model at different time points. A total of 88 rats were divided into five groups and exposed to ACA except for the sham group. To evaluate glomerular function and oxidative stress, serum levels of blood urea nitrogen (BUN) and creatinine (Crtn) and malondialdehyde (MDA) levels in renal tissues were measured. To determine histopathological damage, hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson's trichrome staining were performed. Expression levels of antioxidant enzymes including superoxide dismutase-1 (SOD-1), superoxide dismutase-2 (SOD-2), catalase (CAT), and glutathione peroxidase (GPx) were measured by immunohistochemistry (IHC). Survival rate of the experimental rats was reduced to 80% at 6 h, 55% at 12 h, 42.9% at 1 day, and 33% at 2 days after return of spontaneous circulation. Levels of BUN, Crtn, and MDA started to increase significantly in the early period of CA induction. Renal histopathological damage increased markedly from 6 h until two days post-CA. Additionally, expression levels of antioxidant enzymes were significantly decreased at 6 h, 12 h, 1 day, and 2 days after CA. CA-induced oxidative stress and decreased levels of antioxidant enzymes (SOD-1, SOD-2, CAT, GPx) from 6 h to two days could be possible mediators of severe renal tissue damage and increased mortality rate.

Reference genes for the developing mouse lung under consideration of biological, technical and experimental confounders.

For gene expression analysis, the raw data obtained from RT-qPCR are preferably normalized to reference genes, which should be constantly expressed regardless of experimental conditions. Selection of reference genes is particularly challenging for the developing lung because of the complex transcriptional and epigenetic regulation of genes during organ maturation and injury repair. To date, there are only limited experimental data addressing reliable reference genes for this biological circumstance. In this study, we evaluated reference genes for the lung in neonatal C57BL/6 mice under consideration of biological, technical and experimental conditions. For that, we thoroughly selected candidates from commonly used reference genes side-by-side with novel ones by analyzing publicly available microarray datasets. We performed RT-qPCR of the selected candidate genes and analyzed their expression variability using GeNorm and Normfinder. Cell-specific expression of the candidate genes was analyzed using our own single-cell RNA-sequencing data from the developing mouse lung. Depending on the investigated conditions, i.e., developmental stages, sex, RNA quality, experimental condition (hyperoxia) and cell types, distinct candidate genes demonstrated stable expression confirming their eligibility as reliable reference genes. Our results provide valuable information for the selection of proper reference genes in studies investigating the neonatal mouse lung.

[Social jetlag: possibilities of micronutrient support].

The concept of social jetlag refers to asynchronous communication of a person's biological clock with tempo of modern living, which occurs mainly as a result of intensive work. At the core of social jetlag is sleep deprivation or chronic sleep restriction caused by social factors: pervasive use of electronic solutions and networks, intensive round the clock operation, chronic diseases. The aim of the work was to determine vitamins, minerals, and other micronutrients, the availability of which is important for supporting the organism in case of circadian rhythm sleep disorders and sleep restrictions, the so-called social jetlag. Material and methods. The analysis of 78 sources from PubMed and Google Scholar bibliographic bases was carried out with a detailed analysis of data from the published studies. Results. Circadian rhythm sleep disorders and sleep restrictions affects cognitive functions, increasing risk of anxiety and depressive disorders, enhances processes of chronic inflammation, oxidative stress, cardiometabolic disorders. Scientific evidence has been collected that lack of such elements as magnesium, folates, omega-3 polyunsaturated fatty acids and probiotics in diet can worsening effects of social jetlag and increase the risk of chronic diseases. Preventive course intake of this micronutrients is reasonable in people predisposed to social jetlag. Conclusion. In risk groups of people predisposed to social jetlag, along with diverse diet and adequate nutrition, sleep hygiene, it is necessary to provide targeted supplementation with magnesium, folates, omega-3 polyunsaturated fatty acids and probiotic products.