Chronic pain management in dermatology: pharmacotherapy and therapeutic monitoring with opioid analgesia.
A number of chronic dermatologic conditions may necessitate long-term adjunctive pain management in addition to treatment of the primary skin disease, such as hidradenitis suppurativa, lichen planus, and other systemic diseases associated with significant pain. Adequate management of chronic pain can represent a unique challenge, but remains an integral component of clinical treatment in relevant contexts. For nociceptive pain of moderate to severe intensity, opioid analgesics can be beneficial when other pain management strategies have failed to produce adequate relief. The decision to initiate long-term opioid therapy must be carefully weighed, and individualized treatment plans are often necessary to effectively treat pain while minimizing adverse effects. Part II of this 2-part continuing medical education article will describe the appropriate settings for initiation of opioid analgesia for dermatology patients and detail therapeutic strategies and patient monitoring guidelines.


Liquiritin reduces lipopolysaccharide-aroused HaCaT cell inflammation damage via regulation of microRNA-31/MyD88.
Pressure ulcers are a common issue for people who have limited mobility. This study tested the impact of liquiritin on human keratinocyte HaCaT cell inflammatory damage aroused by lipopolysaccharide (LPS). HaCaT cells were underwent LPS and/or liquiritin incubation. Cell viability, apoptosis and inflammatory molecules interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and cyclooxygenase-2 (Cox-2) expressions, along with nuclear factor kappa B (NF-κB) and c-Jun N-terminal kinase (JNK) pathways activities were tested by MTT assay, Guava Nexin assay, ELISA and western blotting, respectively. qRT-PCR was done for measuring microRNA-31 (miR-31) expression. miR-31 inhibitor was transfected to silence miR-31. Animal pressure ulcers was established on the dorsal skin of adult rats. The effects of liquiritin on wound healing were analyzed by measuring wound closure rates. LPS aroused HaCaT cell inflammatory damage, as evidenced by the decrease of cell viability, increase of cell apoptosis and enhanced expressions of IL-6, TNF-α and Cox-2. Liquiritin protected HaCaT cells against LPS-aroused inflammatory damage through increasing cell viability, decreasing cell apoptosis, and reducing IL-6, TNF-α and Cox-2 expressions. Liquiritin attenuated the LPS-aroused NF-κB and JNK pathways activation in HaCaT cells. Rat pressure ulcers model also confirmed that liquiritin promoted wound healing. In mechanism, miR-31 expression was boosted by liquiritin in HaCaT cells. Silencing miR-31 weakened the impacts of liquiritin on LPS-irritated HaCaT cells. Myeloid differentiation factor 88 (MyD88) was a target of miR-31 in HaCaT cells. This research affirmed the beneficial impact of liquiritin on pressure ulcers. Liquiritin reduced LPS-aroused HaCaT cell inflammatory damage might be implemented via raising miR-31 expression, lowering MyD88 expression, and repressing NF-κB and JNK pathways.


The effects of transient receptor potential cation channel inhibition by BI 1358894 on cortico-limbic brain reactivity to negative emotional stimuli in major depressive disorder.
Abnormal emotional processing in major depressive disorder (MDD) has been associated with increased activation to negative stimuli in cortico-limbic brain regions. The authors investigated whether treatment with BI 1358894, a small-molecule inhibitor of the transient receptor potential cation channel subfamily C leads to attenuated activity in these areas in MDD patients. 73 MDD patients were randomized to receive a single oral dose of BI 1358894 (100 mg), citalopram (20 mg), or matching placebo. Brain responses to emotional faces and scenes were investigated using functional magnetic resonance imaging. Primary endpoints were BOLD signal changes in response to negative faces in cortico-limbic brain regions, i.e. bilateral amygdala (AMY), dorsolateral prefrontal cortex, anterior insula (AI), and anterior cingulate cortex. Secondary endpoints were BOLD signal changes in response to negative scenes. For each region, separate ANOVA models were computed for the comparison of treatments (BI 1358894 or citalopram) vs. placebo. The adjusted treatment differences in the % BOLD signal changes in the faces task showed that BI 1358894 induced signal reduction in bilateral AMY and left AI. In the scenes task, BI 1358894 demonstrated significant signal reduction in bilateral AMY, AI, anterior cingulate cortex and left dorsolateral prefrontal cortex. Citalopram failed to induce any significant reductions in BOLD signal in both tasks. BI 1358894-mediated inhibition of the transient receptor potential cation channel subfamily resulted in strong signal reduction in cortico-limbic brain regions, thereby supporting development of this mechanism of action for MDD patients.


Myopic keratomileusis: initial results and myopic keratomileusis combined with other procedures.
Myopic keratomileusis (MKM) was performed on 58 eyes to correct for moderate to severe myopia. This represents the first consecutive 58 cases I performed. Average follow-up was 11.6 months, with the shortest time being three months. Average preoperative myopia was -11.16 diopters (D) with a range of -5.50 D to -21.62 D. Average postoperative myopia was +0.38 D with a range of -7.75 D to +8.50 D. Selected patients (11) had secondary procedures such as homoplastic MKM, astigmatism procedures, or radial keratotomy. The average postoperative correction for all 58 cases was then +0.11 D with a range of -6.37 D to +4.00 D; 88.5% of patients achieved 20/50 or better uncorrected visual acuity. The procedures, postoperative course, and complications are discussed.


Is Disease Activity in Rheumatoid Arthritis during Pregnancy and after Delivery Predictive for Disease Activity in a Subsequent Pregnancy?
To determine whether disease activity in women with rheumatoid arthritis (RA) in 1 pregnancy is predictive for disease activity in a subsequent pregnancy. In the Pregnancy-induced Amelioration of Rheumatoid Arthritis study, there are prospective data on 27 patients who participated twice. Improvement and deterioration is determined by changes in the Disease Activity Score in 28 joints. Only 4 patients (14.8%) had comparable disease courses in both pregnancies, whereas treatment remained mostly similar. In contrast, a flare postpartum after the first pregnancy was predictive for a flare after the second pregnancy (p = 0.003). RA disease course in following pregnancies cannot be predicted based upon previous pregnancies. However, a flare postpartum seems to predict subsequent flares.


Hyperglycemia facilitates urinary excretion of C-peptide by increasing glomerular filtration rate in non-insulin-dependent diabetes mellitus.
We have evaluated the feasibility of monitoring the 24-hour urinary excretion rate of C-peptide (U-CPR) as a measure of integrated beta-cell function in patients with non-insulin-dependent diabetes mellitus (NIDDM). In 37 normoalbuminuric patients, U-CPR of 117.9 +/- 9.1 micrograms/d (mean +/- SEM) during the poorly controlled glycemic phase (fasting plasma glucose [FPG], 171 +/- 7 mg/dL; hemoglobin A1C [HbA1c], 8.8% +/- 0.4%) was significantly higher than the value of 83.3 +/- 13.7 micrograms/d (P < .001) during the well-controlled phase (FPG, 135 +/- 6 mg/dL; HbA1c, 7.0% +/- 0.2%), although the plasma insulin response to meals was lower during the former phase (53.3 +/- 6.3 microU/mL) versus the latter phase (65.7 +/- 6.6, P < .005). Endogenous creatinine clearance (Ccr) was significantly elevated during the poorly controlled phase (105.4 +/- 7.3 v 88.7 +/- 4.7 mL/min, P < .005). In 26 microalbuminuric patients, the plasma insulin response was greater during good glycemic control, but U-CPR did not differ between the two phases. Ccr was comparable at two phases in this group (92.7 +/- 7.4 v 91.1 +/- 5.9 mL/min, NS). U-CPR correlated positively with Ccr in both groups (r = .593, P < .001 in normoalbuminuria; r = .585, P < .001 in microalbuminuria). In addition, when biosynthetic human C-peptide was infused intravenously at an identical rate in two healthy subjects, resulting steady-state plasma levels of CPR were lower, and fractional U-CPR was higher during the moderately hyperglycemic phase versus the euglycemic phase.(ABSTRACT TRUNCATED AT 250 WORDS)


Risk factors and outcome of Stenotrophomonas maltophilia infection after allogeneic hematopoietic stem cell transplantation: JSTCT, Transplant Complications Working Group.
Stenotrophomonas maltophilia (S. maltophilia) is an aerobic nonfermenting Gram-negative bacillus widely distributed in the environment that has inherent multidrug resistance to beta-lactam and carbapenem antibiotics. S. maltophilia infection (SMI) is known as an important fatal complication following allogeneic hematopoietic stem cell transplantation (HSCT), but its clinical characteristics have not been well clarified. A retrospective study to identify the incidence, risk factors, and outcomes of SMI after allogeneic HSCT was performed using the database of the Japanese nationwide registry, including 29,052 patients who received allogeneic HSCT in Japan between January 2007 and December 2016. A total of 665 patients developed SMI (sepsis/septic shock, 432; pneumonia, 171; other, 62). The cumulative incidence of SMI at 100 days after HSCT was 2.2%. Among risk factors identified for SMI (age ≥ 50 years, male, performance status 2-4, cord blood transplantation [CBT], myeloablative conditioning, Hematopoietic Cell Transplant-Comorbidity Index [HCT-CI] score 1-2, HCT-CI score ≥ 3, and active infectious disease at HSCT), CBT was the strongest risk factor (hazard ratio, 2.89; 95%CI, 1.94-4.32; p < 0.001). The survival rate at day 30 after SMI was 45.7%, and SMI before neutrophil engraftment was significantly associated with poor survival (survival rate 30 days after SMI, 40.1% and 53.8% in patients with SMI before and after engraftment, respectively; p = 0.002). SMI is rare after allogeneic HSCT, but its prognosis is extremely poor. CBT was a strong risk factor for SMI, and its development prior to neutrophil engraftment was associated with poor survival.


Biopolitics of othering during the COVID-19 pandemic.
The COVID-19 pandemic as a global threat caused the introduction of different biopolitical measures accompanied by discourses on otherness, including xenophobic, racist, nationalist, or new orientalist discourses. The aim of this research is to map discourses on otherness during the COVID-19 pandemic. Our general hypothesis is that, despite the differences in social and cultural contexts, discourses on otherness generated during the pandemic legitimized biopolitical actions and/or measures in addition to exacerbating social, political and cultural differences. The research is based on a semi-systematic approach to literature review using Situational Analysis and Sociology of Knowledge Approach to Discourse. In conclusion, we discuss the impact of discourse studies in the context of the global emergency.


CRISPR technology: The engine that drives cancer therapy.
CRISPR gene editing technology belongs to the third generation of gene editing technology. Since its discovery, it has attracted the attention of a large number of researchers. Investigators have published a series of academic articles and obtained breakthrough research results through in-depth research. In recent years, this technology has developed rapidly and been widely applied in many fields, especially in medicine. This review focuses on concepts of CRISPR gene editing technology, its application in cancer treatments, its existing limitations, and the new progress in recent years for detailed analysis and sharing.


Determination of the DNA methylation level in tumor cells by capillary electrophoresis and laser-induced fluorescence detection.
An analytical method to determine the genome-wide DNA methylation in only 100 ng DNA is presented. The analysis is based on DNA isolation and hydrolysis followed by derivatization of the 2'-desoxyribonucleoside-3'-monophosphates with a fluorescence dye (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl ethylene diamine hydrochloride, Bodipy FL EDA). The separation of the derivatives was carried out by micellar electrokinetic chromatography, and laser-induced fluorescence was used for detection. To calculate the methylation level, the derivatization factor and the quantum yields of the Bodipy conjugates of 2'-desoxycytidine-3'-monophosphate (dCMP) and 2'-desoxy-5-methylcytidine-3'-monophosphate (5m-dCMP) were determined by measurement of methylated Lambda DNA. The assignment was made by cochromatography with the synthesized and characterized standard compound 5m-dCMP. After optimization of the method it was possible to determine the methylation level in 100-ng DNA samples with a standard deviation of less than 5%.


Topical Cyclosporin A in the treatment of acute graft rejection: a randomized controlled trial.
Corneal graft rejection is the commonest cause of graft failure. Currently, intensive topical steroid is the treatment for graft rejection.We hypothesized that the use of topical Cyclosporin A (CsA) 0.05%, specifically Restasis (Allergan) in addition to intensive steroids would aid in the reversal and treatment of endothelial graft rejection. In a randomized double masked control study, we recruited 108 patients with acute endothelial graft rejection. They were randomized to two groups. The first group received intensive prednisolone acetate and placebo. The second group received intensive prednisolone acetate and Restasis. There was no difference between the baseline characteristics for the two groups. Nine out of 54 in the placebo group and five out of 54 (16.7% vs. 9.2% P = 0.23) in the treatment group were exited from the study because of worsening signs despite treatment. No significant difference was found between the two groups for time to reversal and resolution. Side-effects of the treatment include increased intraocular pressure and punctate epithelial erosions.These changes most likely relate to the use of intensive prednisolone acetate. The use of commercially available CsA as an adjunct to topical steroids does not appear to improve the outcome of graft rejection.


Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 Patients.
SARS-CoV-2 infection has, as of April 2021, affected >133 million people worldwide, causing >2.5 million deaths. Because the large majority of individuals infected with SARS-CoV-2 are asymptomatic, major concerns have been raised about possible long-term consequences of the infection. Wedeveloped an antigen capture assay to detect SARS-CoV-2 spike protein in urine samples from patients with COVID-19whose diagnosis was confirmed by positive PCR results from nasopharyngeal swabs (NP-PCR+) forSARS-CoV-2. We used a collection of 233 urine samples from 132 participants from Yale New Haven Hospital and the Children's Hospital of Philadelphia that were obtained during the pandemic (106 NP-PCR+ and 26 NP-PCR-), and a collection of 20 urine samples from 20 individuals collected before the pandemic. Our analysis identified 23 out of 91 (25%) NP-PCR+ adult participants with SARS-CoV-2 spike S1 protein in urine (Ur-S+). Interestingly, although all NP-PCR+ children were Ur-S-, one child who was NP-PCR- was found to be positive for spike protein in their urine. Of the 23 adults who were Ur-S+, only one individual showed detectable viral RNA in urine. Our analysis further showed that 24% and 21% of adults who were NP-PCR+ had high levels of albumin and cystatin C, respectively, in their urine. Among individuals with albuminuria (>0.3 mg/mg of creatinine), statistical correlation could be found between albumin and spike protein in urine. Together, our data showed that one of four individuals infected with SARS-CoV-2 develop renal abnormalities, such as albuminuria. Awareness about the long-term effect of these findings is warranted.


Validity and reliability of the MD Anderson dysphagia inventory in English and Chinese in head and neck cancer patients.
Patient-reported outcome measures are important in assessing the impact of dysphagia on quality of life. Our aim was to adapt and examine the cultural validity and reliability of a swallowing-related quality of life measure, the MD Anderson Dysphagia Inventory (MDADI), in English and Chinese, with head and neck cancer patients. We adapted the MDADI to Chinese through formal forward-backward translation. Sixty-six head and neck cancer survivors completed the MDADI, Swallowing Quality of Life (SWAL-QOL) questionnaire and Hospital Anxiety and Depression Scale (HADS) in English or Chinese. Swallowing status was scored on the Functional Oral Intake Scale (FOIS). Seventy-four percent (n = 49) of participants completed a repeat administration of the MDADI for test-retest reliability analysis. The MDADI showed high internal consistency reliability (Cronbach's α , 0.82 ≤ α ≤ 0.94), and test-retest reliability in both English (intraclass correlation coefficient, ICC = 0.81) and Chinese (ICC = 0.72). Criterion validity was established through moderate to strong correlations with relevant SWAL-QOL domains. Convergent validity was determined by significant correlations to the HADS and FOIS. Divergent validity was determined by nonsignificant association to the SWAL-QOL Sleep domain. The MDADI also presented as hypothesised to most known-group theoretical constructs. The MDADI showed good psychometric properties in English and Chinese. This avails a reliable and psychometrically valid MDADI for Chinese speakers.


Hybridization and sexual stimulation in Trichophyton mentagrophytes.
Mating and sexual stimulation tests applied to 132 strains of this dermatophyte isolated in Czechoslovakia revealed among them strains of Arthroderma benhamiae (40 strains of the + mating type, one of the - mating type) and A. vanbreuseghemii (three strains of the + type, seven of the - type). No dependence was found concerning the anamorphic variety (T. mentagrophytes var. granulosum, var. interdigitale, var. mentagrophytes, var. quinckeanum), teleomorphic species, mating type and the clinical localization of dermatophytosis. Plausible reasons of different frequencies of the mating types are discussed.


Developing a psychosocial rehabilitation treatment mall: an implementation model for mental health nurses.
The psychosocial rehabilitation "treatment mall" is a widely accepted method of providing active treatment to patients with serious mental illnesses in psychiatric hospital settings. As a multidisciplinary endeavor, it is important that all clinical disciplines are involved in the development and operation of treatment malls. However, related to their roles as both clinicians and as milieu managers, nurses are crucial in both the development and implementation of such malls. Current literature fails to adequately highlight the role nurses and nursing staff play in treatment malls. Using the treatment mall at Memphis Mental Health Institute as an exemplar, a mall implementation model will be discussed specifically focusing on intra- and interdisciplinary nursing practice.


Multifunctional Nanoparticles Self-Assembled from Small Organic Building Blocks for Biomedicine.
Supramolecular self-assembly shows significant potential to construct responsive materials. By tailoring the structural parameters of organic building blocks, nanosystems can be fabricated, whose performance in catalysis, energy storage and conversion, and biomedicine has been explored. Since small organic building blocks are structurally simple, easily modified, and reproducible, they are frequently employed in supramolecular self-assembly and materials science. The dynamic and adaptive nature of self-assembled nanoarchitectures affords an enhanced sensitivity to the changes in environmental conditions, favoring their applications in controllable drug release and bioimaging. Here, recent significant research advancements of small-organic-molecule self-assembled nanoarchitectures toward biomedical applications are highlighted. Functionalized assemblies, mainly including vesicles, nanoparticles, and micelles are categorized according to their topological morphologies and functions. These nanoarchitectures with different topologies possess distinguishing advantages in biological applications, well incarnating the structure-property relationship. By presenting some important discoveries, three domains of these nanoarchitectures in biomedical research are covered, including biosensors, bioimaging, and controlled release/therapy. The strategies regarding how to design and characterize organic assemblies to exhibit biomedical applications are also discussed. Up-to-date research developments in the field are provided and research challenges to be overcome in future studies are revealed.


New insights into thiamphenicol biodegradation mechanism by Sphingomonas sp. CL5.1 deciphered through metabolic and proteomic analysis.
Biological treatment is an efficient and economical process to remove thiamphenicol (TAP) residues from the environment. The discovery of TAP-degrading bacteria and the decryption of its biodegradation mechanism will be beneficial to enhance the biological removal of TAP. In this study, Sphingomonas sp. CL5.1 was found to be capable of catabolizing TAP as the sole carbon, nitrogen, and energy source. This strain could degrade 93.9% of 25 mg/L TAP in 36 h, and remove about 11.9% of the total organic carbon of TAP. A novel metabolism pathway of TAP was constructed, and the enzymes involved in TAP metabolism in strain CL5.1 were predicted via proteomic and metabolic analysis. TAP was proposed to be transformed to O-TAP via oxidation of C3-OH and DD-TAP via dehydration of C3-OH and dehydrogenation of C1-OH. A novel glucose-methanol-choline (GMC) family oxidoreductase CapO was predicted to be involved in the oxidation of C3-OH. O-TAP was supposed to be further cleaved into DCA, glycine, and PMB. Glycine might be a pivotal direct nitrogen source for strain CL5.1, and it could be involved in nitrogen metabolism through the glycine cleavage system or directly participate in the biosynthetic processes.


Pre-hospital discharge testing after implantable cardioverter defibrillator implantation: a measure of safety or out of date? A retrospective analysis of 975 patients.
The present study evaluates the relevance and additional safety value of pre-hospital discharge (PHD) testing in patients with implantable cardioverter defibrillator (ICD) therapy. From June 1998 to May 2009, 975 patients (830 male, 145 female) with ICD were screened retrospectively for failed PHD and analysed for its consequences, risk factors, and patient characteristics after successful intra-operative testing in the implantation procedure. Pre-hospital discharge testing procedure was performed in 809 cases. No serious adverse events (e.g. death, persistant ventricular fibrillation or ventricular tachycardia, stroke) occurred. The overall incidence of failed PHD was 1.4% (n = 11). The underlying mechanisms were defibrillation threshold failure in 9/11 cases and sensing failure in 2/11 cases. In this study predictors for PHD-failure are: (i) cardiomyopathy other than ischaemic or dilative, (ii) young age, and (iii) small or very large left ventricular end-diastolic diameter ( < 40 or > 65 mm). Particularly, (i) manufacture of device or leads, (ii) lead design, (iii) medical treatment, or (iv) gender have no significant influence on PHD failure.


No Effects of New Zealand Blackcurrant Extract on Physiological and Performance Responses in Trained Male Cyclists Undertaking Repeated Testing across a Week Period.
Anthocyanin supplements are receiving attention due to purported benefits to physiological, metabolic, and exercise responses in trained individuals. However, the efficacy of anthocyanin intake over multiple testing days is not known. We compared a placebo and two doses of anthocyanin-rich New Zealand blackcurrant (NZBC) extract (300 and 600 mg·day-1) on plasma lactate, substrate oxidation, and 16.1 km time trial (TT) performance on three occasions over 7-days in a fed state (day 1 (D1), D4, and D7). Thirteen male cyclists participated in a randomized, crossover, placebo-controlled double-blind design. There was no difference in plasma lactate and substrate oxidation between conditions and between days. A time difference was observed between D1 (1701 ± 163 s) and D4 (1682 ± 162 s) for 600 mg (p = 0.05), with an increment in average speed (D1 = 34.3 ± 3.4 vs. D4 = 34.8 ± 3.4 km·h-1, p = 0.04). However, there was no difference between the other days and between conditions. Overall, one week of intake of NZBC extract did not affect physiological and metabolic responses. Intake of 600 mg of NZBC extract showed inconsistent benefits in improving 16.1 km time trial performance over a week period in trained fed cyclists.


The removal of NO from flue gas by NaOH-catalyzed H2O2 system: Mechanism exploration and primary experiment.
Currently, most advanced oxidation denitrification technologies require long flue gas residence time to obtain ideal NO removal efficiency. The NaOH-catalyzed H2O2 system proposed in this paper can obtain 98% NO removal efficiency under the condition of flue gas residence time of 3 s. The mechanism of NO removal and H2O2 decomposition to O2 were proposed. It was confirmed with ESR (Electron-spin-resonance), inhibitor experiments and UV-Vis spectrophotometer that the main group in the reaction process was·O2- radicals, which reacted with NO to form ONOO-, and ONOO- would be gradually transformed into NO3- and NO2- in the air. The effect of some primary factors on the NO removal efficiency and the percentage of H2O2 decomposition to O2 were also investigated. The increase of initial pH has a positive effect on NO removal, while the promotion of NO removal by increasing H2O2 concentration and reaction temperature is limited and the increase of NO has a negative effect on NO removal. Initial pH has a dual impact on the percentage of H2O2 decomposition to O2, H2O2 concentration and reaction temperature promote the decomposition of H2O2 to O2, while NO concentration has an inhibiting effect on it.


Updates on the Use of Subclinical Atherosclerosis to Predict Risk of Cardiovascular Events in Heterozygous Familial Hypercholesterolemia.
The high variability of cardiovascular risk in heterozygous familial hypercholesterolemia (HeFH) is a challenge for therapeutical management. Subclinical cardiovascular imaging represents a tool to overcome this challenge. The purpose of this review is to update the reader on the most recent findings on the non-invasive detection of atherosclerotic burden by carotid doppler ultrasound (US), coronary artery calcium (CAC) score, and computed tomography coronary angiography (CTCA) for the optimization of risk stratification in HeFH subjects. Carotid ultrasound (US) proved its efficacy in the long-term follow-up of HeFH children treated early on with statins, showing a significant reduction of atherosclerotic progression compared to untreated unaffected siblings. The added value of CAC score has been confirmed to predict the risk of cardiovascular events and improve risk stratification provided by available risk equations in asymptomatic HeFH subjects from large prospective cross-national cohorts. Additionally, CTCA provides detailed information on plaque quality and stability, but its role in primary prevention HeFH subjects needs to be further explored. Cardiovascular imaging for the detection of subclinical atherosclerotic cardiovascular disease in HeFH is a promising tool to improve diagnostic and therapeutical management of this undertreated and late-diagnosed disease.


Throughput-scalable manufacturing of SARS-CoV-2 mRNA lipid nanoparticle vaccines.
Lipid nanoparticles (LNPs) are a potent delivery technology that have made it possible for the recent clinical breakthroughs in mRNA therapeutics and vaccines. A key challenge to the broader implementation of mRNA therapeutics and vaccines is the development of technology to produce precisely defined LNP formulations, with throughput that can scale from discovery to commercial manufacturing and meet the stringent manufacturing standards of the pharmaceutical industry. To address these challenges, we have developed a microfluidic chip that incorporates 1×, 10×, or 256× LNP-generating units that achieve scalable production rates of up to 17 L/h of precisely defined LNPs. Using these chips, we demonstrate that LNP physical properties and potency in vivo are unchanged as throughput is scaled. Our chips are fabricated out of silicon and glass substrates, which have excellent solvent compatibility, compatibility with pharmaceutical manufacturing, and can be fully reset and reused. SARS-CoV-2 mRNA-LNP vaccines formulated by our chips triggered potent antibody responses in a preclinical study. These results demonstrate the feasibility of directly translating microfluidic-generated LNPs to the scale necessary for commercial production.


Critical period for androgenic regulation of soma size of sexually dimorphic motoneurons in rat lumbar spinal cord.
In the rat spinal nucleus of the bulbocavernosus (SNB), androgens are known to act during early critical periods to regulate the number and size of motoneurons that innervate perineal muscles, and to produce sex differences in these attributes. The present study determined the end of the critical period for androgenic regulation of SNB soma size in female rats. Intact female rats received injections of testosterone propionate or oil during 1 of 4 postnatal periods, and were compared to control males and females. In adulthood, all rats were gonadectomized, treated with androgen and then sacrificed. The somatic areas of SNB motoneurons were measured. The results suggest that the soma size is increased by androgen treatment only if it is given before about day 12 after birth.


{4,4'-Dimethyl-2,2'-[(2,2-dimethyl-propane-1,3-di-yl)bis-(nitrilo-methanylyl-idene)]diphenolato}nickel(II) monohydrate.
In the title compound, [Ni(C(21)H(24)N(2)O(2))]·H(2)O, both the complex mol-ecule and the water mol-ecule lie on a twofold rotation axis. The Ni(II) ion is coordinated in a distorted square-planar geometry by the tetra-dentate ligand. The dihedral angle between the two symmetry-related benzene rings is 47.12 (8)°. In the crystal, pairs of symmetry-related O-H⋯O hydrogen bonds form R(2) (2)(6) ring motifs. In addition, there are weak inter-molecular C-H⋯O hydrogen bonds, and π-π stacking inter-actions with a centroid-centroid distance of 3.4760 (8) Å.


Menstrual history of young women exposed in utero to diethylstilbestrol.
The menstrual histories of 218 patients exposed in utero to diethylstilbestrol (DES) were compared with those of 158 control subjects. No significant differences were revealed in the complaint of menstrual irregularities at either the initial or follow-up examination. Age at menarche was the same in both groups, and was the same as found in the United States as a whole. These findings differ from the report of a controlled trial in Chicago which suggests that there is a specific pattern of oligomenorrhea associated with DES exposure.


Association Between Attitudes Toward Trauma Informed Care and Psychological First-Aid Training Experience Among Health Care Professionals in Japan.
Trauma informed care (TIC) is an important approach for people who have experienced trauma. Although psychological first aid (PFA) may be effective training in TIC, no study reported an association between PFA training and TIC. This study aimed to investigate the association between PFA training and attitudes toward TIC among health care professionals in Japan. Japanese health care professionals were recruited for a survey conducted from May 21 to June 18, 2021. TIC was assessed by the Attitudes Related to Trauma Informed Care Scale 10-item short form (ARTIC-10). A question about PFA training participation was originally developed through discussion among researchers. Univariate and multiple linear regression analyses were used to examine the association between the PFA experience and ARTIC-10. In total, 484 (3.6%) health care professionals completed all questions. Among them, 77 (15.9%) had experienced PFA training. Univariate and multiple linear regression analyses showed that PFA experience (B = 0.19, 95% CI: 0.02-0.36, P = 0.03; B = 0.17, 95% CI: 0.01-0.34, P = 0.04) was significantly associated with ARTIC-10. This study was the first to show an association between PFA training and attitudes toward TIC among health care professionals, which was a significant result for future research on PFA training, TIC, and trauma care.


The economic and public health impact of intellectual property licensing of medicines for low-income and middle-income countries: a modelling study.
Non-exclusive voluntary licensing that is access-oriented has been suggested as an option to increase access to medicines to address the COVID-19 pandemic. To date, there has been little research on the effect of licensing, mainly focused on economic and supply chain considerations, and not on the benefits in terms of health outcomes. We aimed to study the economic and health effect of voluntary licensing for medicines for HIV and hepatitis C virus (HCV) in low-income and middle-income countries (LMICs). A robust modelling framework was created to examine the difference between scenarios, with (factual) and without (counterfactual) a Medicines Patent Pool (MPP) licence for two medicines, dolutegravir and daclatasvir. Data were obtained from MPP licensees, as well as a large number of external sources. The primary outcomes were the cost savings and health impact between scenarios with and without MPP licences across all LMICs. Through its licences, MPP had access to the volumes and prices of licensed generic products sold in all covered countries on a quarterly basis. These data informed the volumes, prices, and uptake for the past factual scenarios and were the basis for modelling the future factual scenarios. These scenarios were then compared with a set of counterfactual scenarios in the absence of the studied licences. Cumulatively, between 2017 and 2032, the model's central assumptions predicted an additional uptake of 15·494 (range 14·406-15·494) million patient-years of dolutegravir-based HIV treatments, 151 839 (34 575-312 973) deaths averted, and US$3·074 (1·837-5·617) billion saved through the MPP licence compared with the counterfactual scenario. For daclatasvir-based HCV treatments, the cumulative effect from 2015 to 2026 was predicted to be an additional uptake of 428 244 (127 584-636 270) patients treated with daclatasvir, 4070 (225-6323) deaths averted, and $107·593 (30·377-121·284) million saved with the licence compared with the counterfactual scenario. The chain of effects linking upstream licensing to downstream outcomes can be modelled. Accordingly, credible quantitative estimates of economic and health effects arising from access-oriented voluntary licensing were obtained based on assumptions that early generic competition leads to price reductions that influence procurement decisions and enable the faster and broader uptake of recommended medicines, with beneficial economic and health effects. Unitaid.


Protocols: guidance for good practice.
The use of standardised protocols in patient care is becoming widespread. They offer a positive adjunct to nurses, but can be misused by managers to effect changes in staffing skill mix. This article offers guidance for nurses on the essential criteria a protocol must achieve before being considered acceptable.


The shaping of individual meanings assigned to assistive technology: a review of personal factors.
This review article examines the development of individualized meanings assigned to assistive technology and how these personal meanings influence the integration of assistive technology into daily activities. A review of the published literature regarding assistive technology use and abandonment was conducted by performing two independent searches using 26 search terms and three databases. Publications were reviewed for whether they addressed device use, device abandonment, coping, adjustment, adaptation, values, outcomes and/or cultural issues; 81 publications met these criteria. The evidence suggests that psychosocial and cultural issues influence the shaping of individualized meanings assigned to assistive technology. Theoretical arguments suggest that the process of adapting to disability is another influential factor. The synthesis of evidence and theories suggests that successful integration of assistive technology into daily lives requires potential device users to explore: (1) the meanings they assign to devices; (2) their expectations of assistive technology; (3) the anticipated social costs; and (4) ways to understand that disability is one, but not the defining, feature of one's identity.


Exploring the frame effect.
Probes flashed within a moving frame are dramatically displaced (Özkan, Anstis, 't Hart, Wexler, & Cavanagh, 2021; Wong & Mack, 1981). The effect is much larger than that seen on static or moving probes (induced motion, Duncker, 1929; Wallach, Bacon, & Schulman, 1978). These flashed probes are often perceived with the separation they have in frame coordinates-a 100% effect (Özkan et al., 2021). Here, we explore this frame effect on flashed tests with several versions of the standard stimulus. We find that the frame effect holds for smoothly or abruptly displacing frames, even when the frame changed shape or orientation between the end points of its travel. The path could be nonlinear, even circular. The effect was driven by perceived not physical motion. When there were competing overlapping frames, the effect was determined by which frame was attended. There were a number of constraints that limited the effect. A static anchor near the flashes suppressed the effect but an extended static texture did not. If the probes were continuous rather than flashed, the effect was abolished. The observational reports of 30 online participants suggest that the frame effect is robust to many variations in its shape and path and leads to a perception of flashed tests in their locations relative to the frame as if the frame were stationary. Our results highlight the role of frame continuity and of the grouping of the flashes with the frame in generating the frame effect.


Routine bladder biopsy after bacille Calmette-Guérin treatment: is it necessary?
To evaluate the need for routine biopsy at first follow-up after intravesical bacille Calmette-Guérin (BCG) therapy for superficial transitional cell cancer of the bladder (TCCB). We examined the potential role of voided urine cytology and cystoscopy as screening tools to determine which patients should undergo biopsy. The records of 71 patients with TCCB who received a total of 95 courses of BCG were reviewed. The pathology findings before BCG and the cystoscopic, voided cytologic, and biopsy results after BCG were recorded. In 54 cases, the cystoscopic and/or cytologic findings were abnormal. In 19 (35%) of these 54 cases, TCCB was found on biopsy after BCG. In 41 cases, both cystoscopy and cytology were normal. In 1 of these 41 cases, a small superficial low-grade TCCB was found on biopsy. An abnormality on voided cytology or cystoscopy was more likely to occur after treatment for carcinoma in situ. Patients with papillary TCCB who have negative cystoscopic and negative urine cytologic results can safely be spared routine transurethral bladder biopsy with its associated cost and morbidity. However, patients with carcinoma in situ are very likely to have persistent abnormal cytologic or abnormal cystoscopic findings warranting investigation with biopsy and may benefit from routine scheduled biopsy.


Outcomes of infants with severe bronchopulmonary dysplasia in the pediatric intensive care unit.
Some infants with severe bronchopulmonary dysplasia (sBPD) are referred to higher-level centers for multidisciplinary care, including the pediatric intensive care unit (PICU). However, information regarding these infants is limited in PICUs. We investigated the characteristics and outcomes of preterm infants with sBPD referred to the PICU of a tertiary hospital. This retrospective cohort study included 14 preterm infants with sBPD who were transferred to the PICU beyond 40 weeks' postmenstrual age (PMA) because of weaning failure, from January 1, 2014, to September 30, 2018. The median age at referral was 47.1 weeks (range, 43.6-55.9 weeks), and the median length of stay in the previous neonatal intensive care unit was 154 days (range, 105.8-202.3 days) after birth. After referral the following major comorbidities were found in the patients: large airway malacia, n = 7 (50.0%); significant upper airway obstruction, n = 3 (21.4%); and pulmonary arterial hypertension, n = 8 patients (57.1%). Finally, eight patients (57.1%) were successfully extubated without tracheostomy. Final respiratory support of the patients was determined at a median PMA of 56 weeks (range, 48-63 weeks). Age at referral (P = 0.023) and large airway obstruction (P = 0.028) were significantly related to a decrease in successful extubation. Based on a timely and individualized multidisciplinary approach, some of the prolonged ventilator-dependent infants, even those beyond term age, could be successfully extubated.


Analysis of Runx1 Using Induced Gene Ablation Reveals Its Essential Role in Pre-liver HSC Development and Limitations of an In Vivo Approach.
Hematopoietic stem cells (HSCs) develop in the embryonic aorta-gonad-mesonephros (AGM) region and subsequently relocate to fetal liver. Runx1 transcription factor is essential for HSC development, but is largely dispensable for adult HSCs. Here, we studied tamoxifen-inducible Runx1 inactivation in vivo. Induction at pre-liver stages (up to embryonic day 10.5) reduced erythromyeloid progenitor numbers, but surprisingly did not block the appearance of Runx1-null HSCs in liver. By contrast, ex vivo analysis showed an absolute Runx1 dependency of HSC development in the AGM region. We found that, contrary to current beliefs, significant Cre-inducing tamoxifen activity persists in mouse blood for at least 72 hr after injection. This deferred recombination can hit healthy HSCs, which escaped early Runx1 ablation and result in appearance of Runx1-null HSCs in liver. Such extended recombination activity in vivo is a potential source of misinterpretation, particularly in analysis of dynamic developmental processes during embryogenesis.


INDIAN CASTE SYSTEM: HISTORICAL AND PSYCHOANALYTIC VIEWS.
This paper elucidates the historical origins and transformations of India's caste system. Surveying the complex developments over many centuries, it points out that three positions have been taken in this regard. One suggests that the caste one is born into can be transcended within one's lifetime by performing good deeds. The other declares caste to be immutable forever. And, the third says that one can be reborn into a higher caste if one lives a virtuous life. Moving on to the sociopolitical realm, the paper notes how these positions have been used and exploited. The paper then attempts to anchor the existence and purpose of the Hindu caste system in Freud's ideas about group psychology and Klein's proposals of splitting and projective identification. The paper also deploys the large group psychology concepts of Volkan and the culturally nuanced psychoanalytic anthropology of Roland and Kakar. It concludes with delineating some ameliorative strategies for this tragic problem in the otherwise robust democratic society of India.


Macrolide therapy in Pseudomonas aeruginosa infections causes uL4 ribosomal protein mutations leading to high-level resistance.
Pseudomonas aeruginosa colonizes the cystic fibrosis (CF) airways causing chronic bacterial lung infections. CF patients are routinely treated with macrolides, however, P. aeruginosa is considered insusceptible as consequence of inadequate susceptibility testing leaving resistance mechanism completely overlooked. Here, we investigated a new mechanism of macrolide resistance caused by ribosomal protein mutations. Investigating a longitudinal collection of 529 isolates from CF patients and analysing 5758 protein sequences from different sources, mutations in P. aeruginosa's ribosomal proteins connected to macrolide resistance were identified. Using a modified susceptibility testing protocol, isolates harbouring a mutated uL4 ribosomal protein were tested for resistance against macrolide antibiotics and macrolide-induced quorum sensing modulation. Proteome and ribosome profiling were applied to assess the impact of the mutations on the bacterial physiology. Five uL4 mutations were identified in isolates from different CF patients. Most mapped to the conserved loop region of uL4 and resulted in increased macrolide tolerance (>10-fold relative to wt strains). Greater concentrations (>10-fold) of macrolide antibiotic were needed to inhibit the growth, reduce swimming motility, and induce redox sensitivity of the uL4 mutants. 16 proteins involved in ribosome adaptation displayed altered expression possibly to compensate for the uL4 mutations, which changed the ribosome stoichiometry without negatively affecting bacterial physiology. Macrolide antibiotics should, therefore, be considered as active antimicrobial agents against P. aeruginosa and resistance development should be contemplated when patients are treated with prolonged courses of macrolides. Importantly, improved macrolide susceptibility testing is necessary for the detection of resistant bacteria.


Distribution of visual callosal projection neurons in hamsters subjected to transection of the optic radiations on the day of birth.
The optic radiations of hamsters were transected on the day of birth and visual callosal projections in these animals were traced using retrograde transport of either horseradish peroxidase (HRP) or the fluorescent tracers True blue (TB) or Diamidino yellow (DY) when the animals reached maturity (greater than 45 days of age). In the hemisphere ipsilateral to the neonatal lesion, the distribution of callosal cells was markedly altered. These neurons were almost completely restricted to a continuous band in lower lamina V and the upper portion of layer VI. Anterograde HRP transport to the deafferented hemisphere also revealed an abnormal distribution of callosal terminals. The band of labelling that is located along the 17-18a border in the normals was much broader than is normally the case. In the hemisphere contralateral to the lesion, the distributions of callosal cells and terminals were essentially normal. Labelled neurons were located in the infragranular layers (primarily lower layer V and the upper part of lamina VI) throughout area 17 and also in layers II-IV in the 17-18a border region. Anterograde labelling was visible in layers V and VI throughout the mediolateral extent of the dorsal posterior neocortex and supragranular labelling was restricted to the lateral portion of area 17 and medial 18a. These results suggest that the normal thalamic projection to the visual cortex is necessary for the establishment of the strip of supragranular callosal projection neurons which is normally located in the 17-18a border region, but not for the establishment (or maintenance) of callosal projections by large numbers of neurons in the infragranular laminae. They show further that neonatal transection of the optic radiations results in reduction in the correspondence between the distributions of callosal cells and terminals in the deafferented hemisphere.


Species dependent relaxation of intrapulmonary arteries (IPA) of rabbits, dogs and humans by prostacyclin.
Helically cut strips of successive IPA segments of rabbits, dogs and human patients were set up for isometric recording in vitro. High tone was produced by norepinephrine (NE, 3 microM). This tone was markedly reduced by prostacyclin (PGI2) in the secondary, tertiary and quaternary branches of human and canine pulmonary trunk. The IC50 values for PGI2 ranged from 22 to 503 nM, the human vessels being more sensitive to prostacyclin than canine IPA. Under these conditions, the primary and secondary branches of the rabbit pulmonary trunk were not relaxed by PGI2. The contractile potency of NE was determined in each pulmonary vessel studied. The secondary segments of rabbit IPA were about ten times as sensitive to NE (EC50 for NE: 38 +/- 7 nM) as compared to the secondary IPA from dogs and humans (EC50 values: 370 +/- 84 and 440 +/- 50, respectively). When high tone was induced by equieffective contractile concentrations of NE (3 microM for canine and human IPA and 0.3 microM for rabbit vessels), PGI2 was still less effective (P less than 0.01) in relaxing secondary IPA of rabbits (IC25: 220 +/- 55) than the corresponding segments of dogs and humans (IC25: 51 +/- 12 and 17 +/- 4, respectively). The difference between canine and human vessels was also significant (P less than 0.02). These results indicate that there is an interspecies difference in the sensitivity of IPA to NE and PGI2.


Gender, race, pain, and subjective well-being of adults with spinal cord injury.
Assess the relationship of race and gender with subjective well-being (SWB) and determine if pain severity and pain interference mediated that relationship. Cross-sectional study of 2,416 people with traumatic SCI. Subjective well-being (home life, vocational, and global) was measured by the Life Situation Questionnaire. Pain severity and pain interference were significantly correlated with each SWB domain. Race was initially significantly associated with home life and vocational SWB. Blacks were more likely to report lower scores on home life and vocational SWB than whites. After accounting for pain severity and pain interference, race was still associated with vocational and home life SWB. Gender differences were seen in relation to vocational SWB, even after controlling for pain severity and interference. Pain severity and pain interference only partially mediated SWB. Gender and race were associated with lower vocational SWB. Future research should assess potential explanations for this disparity.


[Loss of heterozygosity on chromosome 3p in thyroid tumors].
To study the loss of heterozygosity (LOH) on chromosome 3p in thyroid tumors. LOH at 11 microsatellite loci was analyzed in 74 cases of thyroid tumors (including 20 follicular adenomas, 24 follicular thyroid carcinomas and 30 papillary thyroid carcinomas) by polymerase chain reaction and silver stain. LOH on chromosome 3p was detected in 71% of follicular thyroid carcinoma (17/24), 30% of the papillary thyroid carcinoma (9/30) and 10% of the follicular adenoma (2/20) case. Two minimal common deleted regions (CDR) (3p26-pter and 3p14.2-3p22) involving significant sites of LOH has identified in follicular thyroid carcinoma. There was also one CDR (3p25. 2-26.1) in papillary thyroid carcinoma. LOH is more frequently identified in follicular thyroid carcinoma than in papillary thyroid carcinoma and follicular adenoma. The 3 CDR on chromosome 3p may harbor tumor suppressor genes involved in the pathogenesis of follicular thyroid carcinoma and papillary thyroid carcinoma.


Evaluation and treatment of sleep disorders in the medical setting.
Sleep disturbances may complicate the clinical presentation of medically ill patients. The assessment and management of sleep disorders in this population requires direct attention to the nature of the relationships between medical illness and sleep disorder. In this paper we present a systematic description of these relationships, which include sleep disturbances secondary to symptoms of a medical illness, sleep disturbances secondary to medical treatment, sleep disorders sharing a similar pathophysiology with medical symptoms, and sleep disturbances and medical symptoms secondary to a psychiatric disorder.


Recurrent venous thrombosis (thrombophlebitis migrans) and carcinoma of the lung.
A case of thrombopheblitis migrans associated with a poorly differentiated adenocarcinoma of the lung is presented. The patient died of a massive pulmonary embolus despite anticoagulant therapy. Disordered fibrinolysis may be the cause of the clotting tendency in this condition.


Hyperactive mTORC1 signaling is unaffected by metformin treatment in aged skeletal muscle.
Appropriate activation of growth signaling pathways, specifically mammalian target of rapamycin complex 1 (mTORC1), is central to muscle mass and metabolism. The goal of these studies was to examine the effects of metformin on mTORC1 signaling in aged skeletal muscle in an attempt to normalize growth signaling. Aged (23m) and young (3m) male mice were fed a low fat diet without or with 0.5% metformin for up to 8 weeks, then mTORC1-related signaling was examined in the plantar flexor complex. Metformin had no significant effect on lowering body weight or muscle mass in aged animals, nor altered p70 S6 Kinase 1 (S6K1) and 4E-binding protein 1 (4E-BP1) phosphorylation. However, it significantly (P < 0.05) reduced body weight and lowered S6K1 and rpS6 phosphorylation in the young. Collectively, these data suggest metformin is ineffective at normalizing growth signaling in aged skeletal muscle.


Duty periods with early start times restrict the amount of sleep obtained by short-haul airline pilots.
Most of the research related to human fatigue in the aviation industry has focussed on long-haul pilots, but short-haul pilots also experience elevated levels of fatigue. The aim of this study was to examine the impact of early start times on the amount of sleep obtained prior to duty and on fatigue levels at the start of duty. Seventy short-haul pilots collected data regarding their duty schedule and sleep/wake behaviour for at least two weeks. Data were collected using self-report duty/sleep diaries and wrist activity monitors. Mixed-effects regression analyses were used to examine the effects of duty start time (04:00-10:00 h) on (i) the total amount of sleep obtained in the 12h prior to the start of duty and (ii) self-rated fatigue level at the start of duty. Both analyses indicated significant main effects of duty start time. In particular, the amount of sleep obtained in the 12h prior to duty was lowest for duty periods that commenced between 04:00 and 05:00 h (i.e. 5.4h), and greatest for duty periods that commenced between 09:00 and 10:00 h (i.e. 6.6h). These data indicate that approximately 15 min of sleep is lost for every hour that the start of duty is advanced prior to 09:00 h. In addition, self-rated fatigue at the start of duty was highest for duty periods that commenced between 04:00 and 05:00 h, and lowest for duty periods that commenced between 09:00 and 10:00 h. Airlines should implement a fatigue risk management system (FRMS) for short-haul pilots required to work early-morning shifts. One component of the FRMS should be focussed on the production of 'fatigue-friendly' rosters. A second component of the FRMS should be focussed on training pilots to optimise sleep opportunities, to identify circumstances where the likelihood of fatigue is elevated, and to manage the risks associated with fatigue-related impairment.


A comparative study on synthesis of AgNPs on cellulose nanofibers by thermal treatment and DMF for antibacterial activities.
Herein we present our research on generation of silver nanoparticles (AgNPs) on cellulose nanofibers by thermal treatment and DMF as reducing agents. The cellulose (CE) nanofibers were prepared by deacetylation of electrospun cellulose acetate (CA) nanofibers which were subsequently silver coated using AgNO3 followed by thermal and DMF induced reduction processes. The samples were characterized with scanning electron microscopy (SEM), Fourier transform infra-red spectroscopy (FTIR), X-ray diffraction spectroscopy (XRD), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and antibacterial assays. Effect of these methods on mechanical properties, thermal stabilities (DTA analysis) and swelling of the CE nanofibers were also studied. Both the processes were effective and efficient in generation of AgNPs on CE nanofibers with higher contents and very good spatial distributions. The XRD, XPS and TEM results evidenced formation metallic AgNPs. TEM images depicted the CE nanofibers highly decorated with spherical AgNPs. The DMF induced process generated AgNPs with comparatively larger sizes. The antibacterial results confirmed excellent antibacterial performance of the CEAgNPs against S. aureus and E. coli. The CEAgNP nanofibers well decorated with AgNPs having good spatial distribution and excellent antibacterial performance suggests CEAgNPs as promising candidate for efficient antimicrobial activities.


The Outcome of Stem Cell-Based Therapies on the Immune Responses in Rheumatoid Arthritis.
Rheumatoid arthritis as a common autoimmune inflammatory disorder with unknown etiology can affect 0.5-1% of adults in developed countries. It involves more than just the patient's joints and can be accompanied by several comorbidities and affect cardiovascular, pulmonary, and some other systems of the human body. Although cytokine-mediated pathways are mentioned to have a central role in RA pathogenesis, adaptive and innate immune systems and intracellular signaling pathways all have important roles in this process. Non-steroidal anti-inflammatory drugs, glucocorticoids, conventional disease-modifying anti-rheumatic drugs, and biological agents are some mentioned medications used for RA. They are accompanied by some adverse effects and treatment failures which elucidates the needing for novel and more powerful therapeutic approaches. Stem cell-based therapies and their beneficial effects on therapeutic processes of different diseases have been founded so far. They can be an alternative and promising therapeutic approach for RA, too; due to their effects on immune responses of the disease. This review, besides some explanations about RA characteristics, addresses the outcome of the stem cell-based therapies including mesenchymal stem cell transplantation and hematopoietic stem cell transplantation for RA and explains their effects on the disease improvement.


The relationship between specific dynamic action (SDA) and growth in the common starfish, Asterias rubens L.
After feeding the metabolic rate of animals rapidly increases to a peak level and thereafter slowly declines to pre-feeding level. This phenomenon has been termed the specific dynamic action of food. The processes causing the increase in metabolism are uncertain. In Asterias rubens there was a close relationship between the magnitude of SDA and growth rate (coefficient of determination=r 2=0.85), suggesting that the increased metabolic expenditure following feeding represent the energetic cost of growth.


[A profound retrograde amnesia of almost 30 years and the role of organic, intentional and psychogenic factors].
A 57-year-old man was referred to the Department of Psychiatry & Psychology of a university hospital because of recurrent depressive episodes. He claimed to have had a total amnesia for approximately the first 30 years of his life following an incident resembling a fugue. This case of a focal retrograde amnesia shows the limitations of a dichotomic view of organic, psychogenic and intentional factors.


Identification and characterization of Toll-like receptor 14d in Northeast Chinese lamprey (Lethenteron morii).
Toll-like receptors (TLRs) play an important role in innate immunity of defense against bacterial or viral pathogens. To study the biological characteristics and functions of the TLR genes, TLR14d was identified from Northeast Chinese lamprey (Lethenteron morii) and named LmTLR14d. LmTLR14d coding sequence (cds) is 3285 bp in length and encodes 1094 amino acids (aa). The results showed that LmTLR14d has the typical structure of TLR molecule, which contains the extracellular domain of leucine-rich repeats (LRR), transmembrane domain, and intracellular domain of Toll/interleukin-1 receptor (TIR). The phylogenetic tree showed that LmTLR14d is a homologous gene of TLR14/18 in bony fish. Quantitative real-time PCR (qPCR) revealed that LmTLR14d was expressed in various healthy tissues, including immune and non-immune tissues. Pseudomonas aeruginosa infection up-regulated LmTLR14d in the supraneural body (SB), gill, and kidney tissues of infected Northeast Chinese lamprey. Immunofluorescence results showed that LmTLR14d was located in the cytoplasm of HEK 293T cells in clusters, and its subcellular localization was determined by the TIR domain. The immunoprecipitation results showed that LmTLR14d could recruit L.morii MyD88 (LmMyD88) but not L.morii TRIF (LmTRIF). Dual luciferase reporter results showed that LmTLR14d significantly enhanced the activity of L.morii NF-κβ (LmNF-κβ) promoter. Furthermore, co-transfection of LmTLR14d with MyD88 significantly enhanced the L.morii NF-κβ (LmNF-κβ) promoter activity. LmTLR14d can induce the expression of inflammatory cytokine genes il-6 and tnf-α downstream of NF-κB signal. This study suggested that LmTLR14d might play an important role in the innate immune signal transduction process of lamprey and revealed the origin and function of teleost-specific TLR14.


Two pyrrole acids isolated from Phyllanthus emblica L. and their bioactivities.
An undescribed pyrrole acid, 1-(4'-methoxy-4'-oxobutyl)-1 H-pyrrole-2,5-dicarboxylic acid (1) and one known pyrrole acid (2) were isolated from the fruits of Phyllanthus emblica. The structures of these compounds were elucidated via the comprehensive analyses of IR, HRESIMS, 1D and 2D spectroscopic data. A series of biological assays revealed that compounds 1 and 2 could inhibit LPS-induced over-production of nitric oxide (NO), interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor-α (TNF-α) by reducing the phosphorylation of extracellular regulated protein kinases (ERK) and c-Jun N-terminal kinases (JNK) in RAW 264.7 cells. Additionally, compounds 1 and 2 were found to reduce lipid deposition and increase the mRNA expression of ATP-binding cassette transporter A1 in oxidized low-density lipoprotein-treated RAW264.7 macrophages.


A simple method to calculate the degree of polymerization of alginate oligosaccharides and low molecular weight alginates.
This study presents a quick, simple and accurate method to calculate the degree of polymerization (DP) of alginate oligosaccharides (AOS) and low molecular weight alginates from the concentration of reducing sugar determined by 3,5-dinitrosalicylic acid (DNS) assay. 1H NMR spectroscopy, mass spectroscopy (MS) and certified standards were used to verify the accuracy of this method, and the results showed DP calculated from DNS assay agreed with the actual DP. This method has great potential to simplify the process of measuring DP of alginate in lab and thus could be incorporated into various researches on alginates in the future. Moreover, similar method could be applied when studying the DP of other oligosaccharides.


Treatment of venous thrombosis at unusual sites.
The literature is filled with randomized controlled trial data to guide most steps in managing patients with deep venous thrombosis of the extremities or pulmonary embolism. Venous thrombosis, however, is not limited to these locations and may involve the cerebral venous sinuses, renal veins, splanchnic veins, and ovarian veins. The causes of these thrombi are often unique to the venous segments involved and typically stem from pathologies of the organs supplied by these veins. Very little randomized controlled trial data exist to guide therapy for these atypical venous thrombi. Treatment should focus on correcting the underlying disease and relieving venous congestion of the involved organ while preserving organ functionality. Although natural history data are limited, recurrence rates for these atypical venous thrombi appear to be relatively low. Indefinite secondary anticoagulant prophylaxis is therefore primarily dictated by the congenital or acquired pathology precipitating the event.


Quality improvement and patient safety: Reality and responsibility from Codman to today.
Quality improvement and patient safety (QIPS) has become increasingly important in the practice of medicine, particularly since the Institute of Medicine's report, "To Err is Human." Despite surgery having been initially at the forefront in instituting QIPS, there has been a lag in promoting its importance until recently. A short history of QIPS is presented along with an introduction to the SQUIRE guidelines used for standardizing QIPS publications. As surgeons we are becoming even more accountable in promoting value in health care. As such, knowledge of QIPS will become an increasingly important component of our future practices and publications.


DNA testing in patients with GH deficiency at the time of transition.
Over the last 10 years, major advances in the understanding of pituitary gland development in the mouse have led to the identification of mutations in a number of genes that then lead to delineation of the phenotype of growth hormone deficiency (GHD), either in isolation (IGHD) or in combination with a number of other hormone deficiencies (CPHD) or syndromic features (e.g., septo-optic dysplasia, SOD). The genetic abnormalities include mutations within: (1) Hesx1 (IGHD, SOD or CPHD); (2) Lhx3 (CPHD with preservation of cortisol secretion and a short stiff neck); (3) Lhx4 (GH, TSH and ACTH deficiency with cerebellar hypoplasia); (4) Prop1 (variable CPHD often associated with pituitary masses); (5) POU1F1 (GH, prolactin and TSH deficiency); (6) GHRHR (IGHD) and (7) GH1 (IGHD). There can be variations in inheritance, phenotype and penetrance patterns. Nevertheless, establishing the genetic diagnosis can help in predicting the evolution of the phenotype and in genetic counselling. Therefore, for these reasons it is recommended that all patients with GHD should undergo testing for genetic mutations within the genes associated with IGHD, CPHD and SOD.


Integrated analysis of single-cell chromatin state and transcriptome identified common vulnerability despite glioblastoma heterogeneity.
In 2021, the World Health Organization reclassified glioblastoma, the most common form of adult brain cancer, into isocitrate dehydrogenase (IDH)-wild-type glioblastomas and grade IV IDH mutant (G4 IDHm) astrocytomas. For both tumor types, intratumoral heterogeneity is a key contributor to therapeutic failure. To better define this heterogeneity, genome-wide chromatin accessibility and transcription profiles of clinical samples of glioblastomas and G4 IDHm astrocytomas were analyzed at single-cell resolution. These profiles afforded resolution of intratumoral genetic heterogeneity, including delineation of cell-to-cell variations in distinct cell states, focal gene amplifications, as well as extrachromosomal circular DNAs. Despite differences in IDH mutation status and significant intratumoral heterogeneity, the profiled tumor cells shared a common chromatin structure defined by open regions enriched for nuclear factor 1 transcription factors (NFIA and NFIB). Silencing of NFIA or NFIB suppressed in vitro and in vivo growths of patient-derived glioblastomas and G4 IDHm astrocytoma models. These findings suggest that despite distinct genotypes and cell states, glioblastoma/G4 astrocytoma cells share dependency on core transcriptional programs, yielding an attractive platform for addressing therapeutic challenges associated with intratumoral heterogeneity.


[Breast cancer screening in Austria: Key figures, age limits, screening intervals and evidence].
In January 2014, the first nationwide quality-assured breast cancer screening program addressing women aged ≥ 40 years was introduced in Austria. As part of the process of developing a patient information leaflet, the Evidence Based Medicine (EBM) Review Center of the Medical University of Graz was charged with the task of assessing the potential benefits and harms of breast cancer screening from the available evidence. Based on these results, key figures were derived for mortality, false-positive and false-negative mammography results, and overdiagnosis, considering Austria-specific incidence rates for breast cancer and breast cancer mortality. Furthermore, the current evidence regarding age limits and screening interval, which were the subjects of controversial public discussions, was analyzed. A systematic search for primary and secondary literature was performed and additional evidence was screened, e. g., evaluation reports of European breast cancer screening programs. On the basis of the available evidence and of the Austrian breast cancer mortality and incidence rates, it can be assumed that - depending on the age group - 1 to 4 breast cancer deaths can be avoided per 1,000 women screened in a structured breast cancer screening program, while the overall mortality remains unchanged. On the other hand, 150 to 200 of these 1,000 women will be affected by false-positive results and 1 to 9 women by overdiagnosis due to the structured breast cancer screening. Therefore, the overall benefit-harm balance is uncertain. If women from 40 to 44 or above 70 years of age are considered, who can also participate in the Austrian screening program, even a negative benefit-harm balance seems possible. However, with the implementation of quality standards in breast cancer screening and the dissemination of a patient information leaflet, an improvement in the medical treatment situation, specifically in terms of informed decision-making, can be expected.


Temporary sterility induced by intrascrotal deposition of silastic-polyvinylpyrrolidone-prostaglandin F2alpha tubes in the rabbit: effect on fetal survival after regain of fertility.
In male rabbits of proven fertility, the intrascrotal deposition of two Silastic-polyvinylpyrrolidone tubes containing 3 mg of prostaglandin F2alpha (PGF2alpha)/tube induced within 2 to 4 weeks temporary sterility which lasted for 10 to 14 weeks. Associated with induced sterility were reduction in testicular weight, increase in abnormal spermatozoa (8% to 78% versus 0 to 3.7%), and reduction in sperm motility along the reproductive tract and in the semen for a period of 6 to 7 weeks. During the period of temporary sterility the weight of the epididymis, the sexual drive, and semen volume remained unaltered. Normal fertility was associated with an increase in testicular weight, reduction in the proportion of abnormal sperm, and improved sperm motility. In addition to an altered spermatogenesis, the integrity of mature spermatozoa seemed to be severely affected after PGF2alpha treatment. The reduced number of viable young sired by males that recovered from temporary sterility (pregnancy wastage 35%) as compared with sham-treated controls (pregnancy wastage 3%) suggests that a small percentage of spermatozoa might still be defective at the time of testing. A longer waiting period might be needed to ensure a completely normal reproductive process.


Posterior Cerebral Artery Pseudoaneurysm, a Rare Complication of Pituitary Tumor Transsphenoidal Surgery: Case Report and Literature Review.
Endoscopic endonasal transsphenoidal surgery for pituitary tumors has been the standard therapy for decades. This approach offers surgeons an effective, safe, and wide exposure to the pituitary gland, with a relatively low mortality rate and acceptable complication rates. However, severe complications, including cerebrospinal fistula, meningitis, neural component injury, and vascular injury, may occur. One of the most common and severe complications is carotid artery injury; however, only 2 posterior cerebral artery injuries with pseudoaneurysm formation have been reported previously. One of them received bypass surgery and recovered well, but the other received endovascular treatment and died of intracranial hypertension. Herein, we report a rare case of iatrogenic pseudoaneurysm formation with hemorrhage after transsphenoidal surgery, in which tumor traction-related adjacent vessel injury was most likely. Aneurysm clipping, vascular bypass, and embolization are considered reasonable choices depending on the patient's condition for iatrogenic aneurysm formation. In our case, no surgical or endovascular intervention was performed, and the aneurysm healed spontaneously 3 weeks later.


Different MicroRNA profiles in Peripheral Blood mononuclear cells from patients with initial-onset and recurrent vogt-Koyanagi-Harada Disease.
Vogt-Koyanagi-Harada (VKH) disease is a common type of uveitis that leads to blindness. The clinical manifestations and treatment solutions are different between initial-onset and recurrent VKH. Therefore, identifying the microRNA (miRNA) profiles from initial-onset and recurrent VKH patients may shed light on the molecular mechanisms underlying the pathogenesis of VKH disease. RNAs isolated from peripheral blood mononuclear cells (PBMCs) from patients with initial-onset VKH, recurrent VKH, and healthy individuals were subjected to high-throughput miRNA sequencing. Pairwise analysis of miRNA sequencing data between groups was conducted to identify differentially expressed miRNAs (DEMs), which were verified using real-time quantitative polymerase chain reaction. After receiver operating characteristic analyses, we found that hsa-miR-4664-3p, hsa-miR-7704, hsa-miR-4504, and hsa-miR-206 may serve as biomarkers of different VKH stages. DEMs were classified into three groups based on their differential expression: DEMs in initial-onset stage, DEMs in recurrent stage, and DEMs common between both VKH stages (shared DEMs). Pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes identified the mitogen-activated protein kinase, tumor necrosis factor, and mechanistic target of rapamycin kinase pathways as significantly enriched among the target genes of recurrent stage and shared DEMs. Furthermore, we mapped a network of competing endogenous RNAs for hsa-miR-206, which we used to identify putative targets for VKH treatment. Hsa-miR-4664-3p, hsa-miR-7704, hsa-miR-4504, and hsa-miR-206 may serve as biomarkers for different stages of VKH. Additionally, our competing endogenous RNA network of hsa-miR-206 provides a new direction for VKH treatment.


Effects of thyroid hormones on humoral and cell-mediated immune responses in the domestic fowl (Gallus domesticus).
We investigated the effect of raising and lowering circulating thyroid hormones in young domestic fowl on antibody production and the responses of peripheral blood lymphocytes (PBL) to the mitogens concanavalin A (con A) and phytohaemagglutinin (PHA). Circulating thyroid hormones were reduced by treatment with the goitrogen, methimazole, and raised by giving implants containing thyroxine (T4) and/or triiodothyronine (T3). Raising or lowering circulating thyroid hormones had no significant effect on peak antibody titers, though the decline in titer was slower in goitrogen-treated birds. Lowering circulating thyroid hormones caused a significant increase in the response to con A that was prevented by hormone replacement. There was no effect on the response to PHA and raising circulating hormones had no effect on the responses to con A or PHA. It is suggested that stress-induced changes in thyroid hormones could modulate cell-mediated immune responses.


Features of foreign proteins affecting their retrograde transport in axons of the visual system.
The retrograde axoplasmic transport of foreign proteins in the rat visual system shows certain specificities. The molecular features of these proteins which may underlie their entry into the retrograde phase have been examined using biochemical and morphologic techniques. Of the isoenzymes of horseradish peroxidase (HRP), the basic isoenzyme C is strongly transported, while the acidic isoenzymes Abeta and Aalpha are transported weakly and not at all, respectively. Decreasing the isoelectric point (pI) of isoenzyme C from 8.2 to 4.4 decreases its transport, but a basic pI is not the sole requisite for transportability since two other basic peroxidases (turnip isoenzyme P7 and lactoperoxidase) are not transported in retrograde. The sugar component as a whole of isoenzyme C does not appear to be required for determining transport. Isoenzyme C and the other proteins which are transported enter multivesicular bodies in axons and axon terminals, as well as synaptic and coated vesicles and fine tubules in axon terminals. The non-transported proteins enter only the vesicular organelles thought to be involved in neurotransmitter recycling in axon terminals and do not enter multivesicular bodies. Thus the two systems of axonal membraneous compartments involved in local synaptic recycling versus the retrograde phase of transport do not show the same specificity of uptake of extracellular tracers and can be dissociated by the experimental use of these peroxidases.


Use of sensitized luminescence of lanthanides in analysis of drugs.
The sensitization of the Tb(III) and Eu(III) ions luminescence by drugs, the pyrocatechol, naphthyridine and heterocyclic aromatic acid derivatives, were studied. It was shown that a result of intramolecular energy transfer from the ligand molecule to the lanthanide ion increases the luminescence intensity of the latter by 10(8)-10(10) times. The luminescence properties of the complexes in solutions were investigated. The highly sensitive methods for luminescence determination of dopegyt, levodopum, dophaminum, nevigramon, furosemidum and cinchophenum were developed. The detection limits of the drugs are 0.0005, 0.02, 0.5, 0.01, 0.05 and 0.1, respectively.


Photo-compact-disk-based optical correlator.
A joint-transform correlator employing a recently available inexpensive photo-compact-disk player is described. This is a realistic optical-disk-based correlator based on currently available technology.


Activation of ALDH2 with ethanol attenuates diabetes induced myocardial injury in rats.
This study assessed changes in myocardial ALDH2 expression in the diabetic rat, in particular the diabetic rat pretreated with ALDH2 activator ethanol (EtOH). The rats were divided into six groups: control, EtOH control, diabetic rat at 4th week (DM4W), 8th week (DM8W), 12th week (DM12W) and EtOH+DM8W groups. Compared with control group, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) levels were increased in DM groups. HbA1c level in DM12W group was higher than in DM4W group, HbA1c level in EtOH+DM8W group was lower than in DM8W group. Compared with control group, there were no changes of LVDP, HR and ±dp/dtmax in DM4W group, but there were decreased in DM8W and DM12W groups, and increased in the EtOH+DM8W group. In DM groups, SOD activity, ALDH2 mRNA and protein levels were reduced, MDA content was increased compared with control group; which decreased further as diabetes progressed. Compared with DM8W group, SOD and ALDH2 in EtOH+DM8W group was increased, MDA was decreased. Our results indicated with the development of diabetes, myocardial ALDH2 expression was further decreased accompanying decreased ventricular function. However, activation of ALDH2 can decrease diabetes induced myocardial injury. ALDH2 may be one key endogenous cardiac protective factor in diabetic individuals.


The Goeckerman regimen in two psoriasis day care centers.
Three hundred patients with severe psoriasis were treated with the Goeckerman regimen in two different day care centers. Each patient was personally evaluated and followed by us for a period of 1 year or longer in an effort to determine accurately clearing of the skin, side effects, and length of remission. The average duration of treatment to produce over 90% clearing of the skin was 18 days. Ninety percent of the patients remained clear for a minimum of 8 months, and 73% were clear for 1 year or longer. The average total body dosage of ultraviolet B (UVB) needed to clearing was 1.96 joules/cm2. Side effects were minimal, and there was no increase in skin cancer. The cost-effectiveness of the regimen in a day care center is comparable to psoralens and ultraviolet A (PUVA) therapy.


Central sensitization predicts greater fatigue independently of musculoskeletal pain.
To test whether central sensitization was associated with greater fatigue, independently of musculoskeletal pain. 2477 prospective cohort study participants completed a baseline questionnaire comprising the Chalder Fatigue Scale (CFQ), pain, demographics, physical activity, anxiety, depression and medication use. In a clinical assessment of 290 (11.7%) participants, central sensitization was measured by the wind-up ratio test at the hand (WUR-H) and foot (WUR-F). Bioelectric impedance determined proportion body fat. All participants were followed up 12 months later, at which time they completed the CFQ. Linear regression, with inverse probability sampling weights, tested the relationship between WUR at baseline and CFQ at 12 months, adjusted for baseline CFQ, demographics, lifestyle factors, mental health and baseline pain. At baseline, the median interquartile range WUR-H and WUR-F were similar (2.3 (1.5, 4.0) and 2.4 (1.6, 3.9) respectively) and did not differ by sex (difference WUR-H: -0.29, 95% confidence interval -1.28-0.71; WUR-F: -0.57 (-1.50-0.36) or age(WUR-H: -0.53, -1.49-0.43; WUR-F:-0.08, -0.98-0.82). WUR-H scores (β = 0.11, 95% confidence interval: 0.07-0.16) and WUR-F scores (0.13, 0.08-0.17) were positively associated with CFQ scores at follow-up, independently of baseline CFQ and other covariates. These associations were not explained by baseline pain. Fatigue was predicted by central sensitization, independently of the presence of pain. For those seeking to treat fatigue, the benefit of interventions that reduce central sensitization should be investigated.


Lead and noise exposures at eight Chinese registered electronics recycling facilities.
The purpose of this study was to assess employees' exposure to lead and noise, and to recommend control strategies for reducing these exposures at eight registered electronics recycling facilities in Eastern China. Jiangsu Provincial Center for Disease Control and Prevention (JSCDC) performed a walkthrough and review of health and safety programs during a first visit and conducted full-shift personal and area air monitoring for lead, as well as personal noise exposure measurements on a second visit. Monitoring was performed over two work shifts for a total of 168 employees. Results indicated that employees working at glass breaking and cathode ray tubes dismantling were overexposed both to noise and lead. Airborne lead concentration ranged from 0.1 to 148 μg/m3; and 4 of the 101 samples were above the Chinese permissible exposure limit of 50 μg/m3. Overexposures to lead involved cathode ray tubes dismantling and glass breaking. Employees working at plastics shredding and glass breaking areas were overexposed to noise. Full-shift time-weighted average noise levels ranged from 64 to 107 dBA; and 85 of the 123 samples were above the Chinese permissible exposure limit of 85 dBA. Control measures to reduce exposure to lead and noise, including improvements in their lead protection and hearing conservation programs, at these electronics recycling facilities were recommended.


Glycolysis-dependent antimetabolities: possible improvement in antineoplastic selectivity.
The increased rate of glycolysis in neoplastic cells may be used to design tentatively antimetabolites whose detoxification would be faster in normal cells. Pyruvo-substituted nucleotides are examined in this respect and their expected differential metabolism outlined.


Improving the understanding of oligonucleotide-nanoparticle conjugates using DNA-binding fluorophores.
A novel fluorescent-based method for characterisation of oligonucleotide-nanoparticle conjugates (ONPCs) is reported. We exploit the ability of the double-stranded DNA-binding dye, SYBR Green I, to develop a powerful analytical tool to investigate the melting properties and hybridisation behavior of ONPCs as well as their corresponding DNA-mediated assemblies.


Integrating complementary and alternative medicine into conventional primary care: the patient perspective.
The aim of this study was to explore perspectives on integrating complementary and alternative medicine (CAM) into the conventional primary care setting among patients treated at a large academic family medicine clinic in Texas. We developed and administered a multiple choice questionnaire to evaluate perspectives of 502 patients on integrating CAM into the conventional primary healthcare system. All collected data were statistically analyzed to evaluate responses. Among study participants, 66% indicated that they had used CAM treatments during the past year, 77% responded that they would be interested in using CAM during the next year, and 55.4% replied that they would like CAM therapies to be provided in their primary care clinic. The use of CAM in primary care settings in southern Texas is widespread. However, in this primary care setting, patients would like their family physician to provide and supervise these therapies. Patients believe that there is an increased need for family physician involvement in providing and supervising CAM treatments. Our findings are preliminary but can provide a basis for multicenter, cross-cultural studies to further evaluate the patient perspective on the process of integrating CAM into the conventional primary healthcare system so that healthcare policy makers can better address public need.


Are relationships between impulsivity and depressive symptoms in adolescents sex-dependent?
Both depressive symptomology and impulsivity are common during adolescence and are associated with various negative life outcomes. The potential sex-dependent nature of relationships between these constructs needs further exploration in order to understand their complexities. This cross-sectional study examined how levels of these constructs may differ by sex. Additionally, we investigated whether sex moderates relationships between adolescents' depression symptoms and different facets of impulsivity. 156 adolescents (M age = 17.37, SD = 1.91, 59% female) completed self-report measures of their demographics, depression symptoms, and impulsivity. Multiple Analysis of Covariance (MANCOVA) assessed mean differences in depression symptoms and impulsivity by sex and race/ethnicity. Moderation analyses examined how sex may indirectly affect relationships between depression symptoms to predict attentional, motor, and non-planning impulsivity facets, as well as overall trait impulsivity. Correlations between depression symptoms and impulsivity scores were significant. Baseline depression symptoms were significantly higher among females (M = 9.53) compared to males (M = 6.68). Moderation effects of sex were not significant for attentional, motor, or overall trait impulsivity. However, sex moderated relations between depression symptoms and non-planning impulsivity, such that adolescent males showed higher levels of non-planning impulsivity when they reported high levels of depressive symptoms (B = .32, p < .01). This relationship was not significant for females. While adolescent females may be more prone to depression, adolescent males may be more likely to experience non-planning impulsivity when experiencing symptoms of depression. The results of this study extend the literature regarding sex differences in vulnerabilities between these constructs. We suggest interventions targeting non-planning impulsivity may be especially salient for adolescent males reporting high levels of depressive symptoms.


The association between 2D:4D ratio and cognitive empathy is contingent on a common polymorphism in the oxytocin receptor gene (OXTR rs53576).
Both testosterone and oxytocin influence an individual's accuracy in inferring another's feelings and emotions. Fetal testosterone, and the second-to-forth digit ratio (2D:4D) as its proxy, plays a role in social cognitive development, often by attenuating socio-affective skill. Conversely, oxytocin generally facilitates socio-affiliative and empathic cognition and behavior. A common polymorphism in the oxytocin receptor gene, OXTR rs53576, has been repeatedly linked with psychosocial competence, including empathy, with individuals homozygous for the G allele typically characterized by enhanced socio-cognitive skills compared to A allele carriers. We examined the role of oxytocin and testosterone in collectively contributing to individual differences in cognitive empathy as measured by Baron-Cohen's "Reading the Mind in the Eyes" task (RMET). Findings are based on a large cohort of male and female students (N=1463) of Han Chinese ethnicity. In line with existing literature, women outperformed men in the RMET. Men showed significantly lower 2D:4D ratio compared to women, indicating higher exposure to testosterone during the prenatal period. Interestingly, variation in the OXTR gene was found to interact with 2D:4D to predict men's (but not women's) RMET performance. Among men with GG allelic variation, those with low fetal testosterone performed better on the RMET, compared to men with GG and high fetal testosterone, suggesting greater identification of another's emotional state. Taken together, our data lend unique support to the mutual influence of the oxytocin and testosterone systems in shaping core aspect of human social cognition early in development, further suggesting that this effect is gender-specific.


Simultaneous electrochemical degradation of tetracycline and metronidazole through a high-efficiency and low-energy-consumption advanced oxidation process.
With the increasing complexity of water environment pollution, it is becoming ever more practical to study the simultaneous removal of multiple pollutants in water. Electrochemical advanced oxidation technology is considered to be one of the most promising green approaches for the degradation of organic pollutants. Herein, Ti3+ and oxygen vacancies (VO) self-doped TiO2-x nanotube array electrodes are employed to investigate the simultaneous degradation and an energy consumption assessment for the effective removal of the antibiotics tetracycline (TC) and metronidazole (MNZ). The electrocatalytic performance of the nanotube arrays prepared at different reduction times is significantly different. The electrochemical reduction of TiO2 nanotube arrays for 10 min presents the best degradation performance for TC and MNZ. When a mixed solution of TC and MNZ is simultaneously degraded, the removal rate of TC (50 mg L-1) and MNZ (50 mg L-1) within 3 h reaches 100%, while the chemical oxygen demand (COD) removal rate is 79.1%. The energy consumption is significantly reduced compared to the degradation of a single substance. Simultaneously, the current utilization rate of the electrochemical degradation system is also significantly improved, with a specific energy consumption of only 85.78 kWh kg-1 and an average current efficiency that can reach 20.2%.


Investigation of MDR1-overexpressing cell lines to derive a quantitative prediction approach for brain disposition using in vitro efflux activities.
MDR1-overexpressing Lilly Laboratories cell porcine kidney 1 cells (LLC-PK1-MDR1) and Madin-Darby canine kidney cells (MDCK-MDR1) are widely used in drug discovery to evaluate the in vivo relevance of MDR1-mediated efflux. However, as the in vitro efflux ratio (ER) of these cell lines are variable among research facilities, the in vitro ER of these cell lines that would affect quantitative predictivity of brain disposition has not been fully clarified. The aim of this study was to examine the effect of ER on the quantitative predictivity of brain disposition toward compounds with MDR1 and/or breast cancer resistant protein (BCRP) liabilities. Test compounds including internal molecules and five typical substrates of MDR1 and/or BCRP were assessed via an in vitro transporter assay to determine the corrected flux ratio (CFR) and an in vivo animal study using wild-type (WT) and Mdr1a (-/-)/Bcrp(-/-) (dual KO) rats. To assess the in vivo ER for MDR1, the two cell lines LLC-PK1-MDR1 and MDCK-MDR1 were used. After intravenously administering 29 test compounds to rats, the Kp,brain ratio (ratio of Kp,brain,WT to Kp,brain,dual KO), which is considered to be the unbound plasma-to-brain ratio (Kp,uu,brain) that does not require correction for protein binding in both plasma and brain, was determined by measuring their concentrations in the plasma and brain. The Kp,brain ratio of these compounds was predicted by fitting scaling factor that was extrapolated from the in vitro to in vivo ER for MDR1 and BCRP, defined as α and β, respectively. Kp,brain ratio values of 83% and 68% of compounds were predicted by using MDCK-MDR1 and LLC-PK1-MDR1, respectively, within a 2-fold range of the actual corresponding values. The α predicted from CFRs of MDCK-MDR1 was 47-fold smaller than that of LLC-PK1-MDR1; however, a dramatic change in β was not observed. This result appears to be consistent with the data of in vitro transport activity of MDR1, which was estimated to be ~28-fold higher in MDCK-MDR1 than in LLC-PK1-MDR1 by correlation analysis with CFR. Through this study, we revealed that 1) brain disposition in rats was well-predicted by considering the in vitro efflux activities for both MDR1 and BCRP, and 2) MDCK-MDR1 was the superior cell line for the quantitative prediction of brain disposition.


How incubation temperature influences the physiology and growth of embryonic lizards.
Eggs of two small Australian lizards, Lampropholis guichenoti and Bassiana duperreyi, were incubated to hatching at 25 degrees C and 30 degrees C. Incubation periods were significantly longer at 25 degrees C in both species, and temperature had a greater effect on the incubation period of B. duperreyi (41.0 days at 25 degrees C; 23.1 days at 30 degrees C) than L. guichenoti (40.1 days at 25 degrees C; 27.7 days at 30 degrees C). Patterns of oxygen consumption were similar in both species at both temperatures, being sigmoidal in shape with a fall in the rate of oxygen consumption just prior to hatching. The higher incubation temperature resulted in higher peak and higher prehatch rates of oxygen consumption in both species. Total amount of oxygen consumed during incubation was independent of temperature in B. duperreyi, in which approximately 50 ml oxygen was consumed at both temperatures, but eggs of L. guichenoti incubated at 30 degrees C consumed significantly more (32.6 ml) than eggs incubated at 25 degrees C (28.5 ml). Hatchling mass was unaffected by either incubation temperature or the amount of water absorbed by eggs during incubation in both species. The energetic production cost of hatchling B. duperreyi (3.52 kJ x g(-1)) was independent of incubation temperature, whereas in L. guichenoti the production cost was greater at 30 degrees C (4.00 kJ x g(-1)) than at 25 degrees C (3.47 kJ g(-1)). Snout-vent lengths and mass of hatchlings were unaffected by incubation temperature in both species, but hatchling B. duperreyi incubated at 30 degrees C had longer tails (29.3 mm) than those from eggs incubated at 25 degrees C (26.2 mm). These results indicate that incubation temperature can affect the quality of hatchling lizards in terms of embryonic energy consumption and hatchling morphology.


Physical therapy management of an individual with post-COVID fatigue considering emotional health in an outpatient setting: A case report.
The purpose of this case report is to provide a plan of care with an emphasis on patient education and consideration of emotional health for a patient with post-COVID fatigue in an outpatient setting. A 50-year-old woman, ten-weeks post-COVID syndrome, participated in an examination that revealed deficits in exercise capacity, strength, breathing pattern, mild depression, emotional breakdown, and mild anxiety accompanied by "brain fog" with activity. Her primary complaint was fatigue with ordinary activities around her home that impeded her from returning to work. On examination, scores included six-minute walk test distance (6MWD): 79.5 m, UCSD Shortness of Breath Questionnaire (SOBQ): 72/120, and Patient Health Questionnaire (PHQ-9): 6/27. The patient participated in 20 biweekly sessions with a focus on patient education, supporting emotional health, aerobic training, strengthening exercises, breathing exercises, and home exercise program. At discharge, the patient's exercise capacity, muscle strength, dyspnea, and depression improved, beyond the MCID/MID values, 6MWD: 335 m, SOBQ: 34/120; and PHQ-9 :1/27. The patient had no anxiety with activity and reported confidence to resume activities, allowing her to return to work safely. Following an intervention that addressed emotional needs with physical symptoms, our patient with post-COVID fatigue showed substantial improvements in exercise capacity, muscle strength, dyspnea, and depression. This highlights the consideration of psychosocial well-being in our plan of care for this population.


Two new species of Aphis (Toxoptera) Koch (Hemiptera, Aphididae) from China.
Two new aphid species, Aphis (Toxoptera) fafuensis Cheng & Huang, sp. nov., feeding on Adinandramillettii (Pentaphylacaceae) from Fujian, China, and Aphis (Toxoptera) sennae Cheng & Huang, sp. nov., feeding on Sennabicapsularis (Fabaceae) from Yunnan, China, were described. Morphological characters and molecular data supported the taxonomic position of the new species within the subgenus Aphis (Toxoptera). A key for identifying species of apterous viviparous females in this subgenus is provided.


Customization of milled zirconia copings for all-ceramic crowns: a clinical report.
Generically milled zirconia copings for all-ceramic crowns may not provide optimal thickness and form for the coping or the porcelain veneer. This article describes the customization of milled zirconia copings to provide even and controlled porcelain thickness with the aim of decreasing cohesive porcelain fracture and other failures. A full-contour waxing and cut back in conjunction with a dual-scan technique was used to ensure adequate coping thickness, adequate, even porcelain thickness, and butt joints at the porcelain-to-coping junctions.