Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells.

The scarcity of tissue-specific stem cells and the complexity of their surrounding environment have made molecular characterization of these cells particularly challenging. Through single-cell transcriptome and weighted gene co-expression network analysis (WGCNA), we uncovered molecular properties of CD133(+)/GFAP(-) ependymal (E) cells in the adult mouse forebrain neurogenic zone. Surprisingly, prominent hub genes of the gene network unique to ependymal CD133(+)/GFAP(-) quiescent cells were enriched for immune-responsive genes, as well as genes encoding receptors for angiogenic factors. Administration of vascular endothelial growth factor (VEGF) activated CD133(+) ependymal neural stem cells (NSCs), lining not only the lateral but also the fourth ventricles and, together with basic fibroblast growth factor (bFGF), elicited subsequent neural lineage differentiation and migration. This study revealed the existence of dormant ependymal NSCs throughout the ventricular surface of the CNS, as well as signals abundant after injury for their activation.

Implications of anesthesia and vaccination.

The current COVID-19 pandemic has had a global impact on vaccination rates. Delays in routine healthcare and immunization have led to a rise in concerns about resurgence of vaccine-preventable diseases around the world. With the release and distribution of COVID-19 vaccines, plans to improve immunization rates need to be explored and implemented across disciplines. One approach would be the consideration of perioperative vaccinations; however, the effects of anesthesia and surgery on the immune response and complications associated with vaccination during the perioperative period are still poorly understood, and opinions are divided. To ascertain the value of a perioperative vaccination program, it is important to understand the basics of immunization and common vaccinations; the potential vaccine complications in the pediatric cohort; the implications of anesthesia and surgery on the immune response; and current recommendations. In addition, we believe it is important to discuss the logistics and feasibility of coordinating perioperative immunization should this become a regular opportunity.

Natural History of Pressure Injury Among Ethnically/Racially Diverse Nursing Home Residents: The Pressure Ulcer Detection Study.

The current observational study provides descriptive data on 270 pressure injuries (PrIs) among 142 racially/ethnically diverse nursing home (NH) residents over 16 weeks. Weekly assessments were conducted with the Bates-Jensen Wound Assessment Tool. NH data were obtained from public government websites. NH, resident, and PrI characteristics across race/ethnicity groups were compared using analysis of variance and chi-square. Participants were 62% female and 89% functionally dependent. More Black and Asian individuals had peripheral vascular disease. More Black individuals had persistent trunk and Stage 4 PrIs. Black and Hispanic individuals had normal skin color surrounding PrIs. More Asian individuals had PrIs surrounded by purple/red discolored skin. More Black individuals' heel PrIs were unstageable, necrotic, and showed no granulation. Black and Hispanic individuals exhibited more deep tissue injury. No NH or prevention differences existed. Health disparities found validate administrative data results. Differences in PrI characteristics should be further examined among diverse NH residents. [Journal of Gerontological Nursing, 47(3), 37-46.].

Progressive B Cell Loss in Revertant X-SCID.

We report the case of a patient with X-linked severe combined immunodeficiency (X-SCID) who survived for over 20 years without hematopoietic stem cell transplantation (HSCT) because of a somatic reversion mutation. An important feature of this rare case included the strategy to validate the pathogenicity of a variant of the IL2RG gene when the T and B cell lineages comprised only revertant cells. We studied the X-inactivation of sorted T cells from the mother to show that the pathogenic variant was indeed the cause of his SCID. One interesting feature was a progressive loss of B cells over 20 years. CyTOF (cytometry time of flight) analysis of bone marrow offered a potential explanation of the B cell failure, with expansions of progenitor populations that suggest a developmental block. Another interesting feature was that the patient bore extensive granulomatous disease and skin cancers that contained T cells, despite severe T cell lymphopenia in the blood. Finally, the patient had a few hundred T cells on presentation but his TCRs comprised a very limited repertoire, supporting the important conclusion that repertoire size trumps numbers of T cells.

Phosphodiesterase PdeD, dynacortin, and a Kelch repeat-containing protein are direct GSK3 substrates in Dictyostelium that contribute to chemotaxis towards cAMP.

The migration of cells according to a diffusible chemical signal in their environment is called chemotaxis, and the slime mold Dictyostelium discoideum is widely used for the study of eukaryotic chemotaxis. Dictyostelium must sense chemicals, such as cAMP, secreted during starvation to move towards the sources of the signal. Previous work demonstrated that the gskA gene encodes the Dictyostelium homologue of glycogen synthase kinase 3 (GSK3), a highly conserved serine/threonine kinase, which plays a major role in the regulation of Dictyostelium chemotaxis. Cells lacking the GskA substrates Daydreamer and GflB exhibited chemotaxis defects less severe than those exhibited by gskA- (GskA null) cells, suggesting that additional GskA substrates might be involved in chemotaxis. Using phosphoproteomics we identify the GskA substrates PdeD, dynacortin and SogA and characterize the phenotypes of their respective null cells in response to the chemoattractant cAMP. All three chemotaxis phenotypes are defective, and in addition, we determine that carboxylesterase D2 is a common downstream effector of GskA, its direct substrates PdeD, GflB and the kinases GlkA and YakA, and that it also contributes to cell migration. Our findings identify new GskA substrates in cAMP signalling and break down the essential role of GskA in myosin II regulation.

Secondhand tobacco exposure is associated with nonalcoholic fatty liver disease in children.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in children in the United States, and prevalence rates are rising. Smoking is associated with NAFLD, but the association of secondhand smoke exposure with NAFLD is unknown. AIMS: To investigate the association of secondhand tobacco exposure with NAFLD in children. METHODS: We surveyed parents/guardians of 304 children aged 3-12 years who had received an abdominal ultrasound at Penn State Hershey Medical Center. The survey addressed demographics, medical history, secondhand tobacco exposure, activity level, screen viewing time and other environmental exposures. A pediatric radiologist and sonographer reviewed the ultrasounds to grade the presence of bight liver compatible with NAFLD. We conducted logistic regression analysis to assess the association of secondhand tobacco exposure and NAFLD. RESULTS: 54% of eligible potential participants responded to the survey. Fatty liver was present in 3% of the children. Increasing child age was associated with increased odds of NAFLD (OR 1.63 95% CI 1.1, 2.4). Reported child obesity was associated with increased odds of NAFLD (OR 44.5 95% CI 5.3, 371.7). The rate of NAFLD was higher in the smoke exposed group (6.7% vs. 1.7%). For every extra pack per day smoked at home, the odds of a child having NAFLD increased 1.8 times (AOR 1.8, 95% CI 1.2, 2.8), and any exposure increased a child's odds of NAFLD four-fold (AOR 4.0, 95% CI 1.02, 15.8). CONCLUSION: We found an association of secondhand smoke exposure and NAFLD in children. This may represent an area for future prevention efforts.

Color and newborn intensive care unit design: executive summary.

Research on color in the design of healthcare settings is minimal. This paper provides an executive summary of a recent review on this topic, focusing on application to newborn intensive care units. The review focuses on the following question: Does the use of color in the design of the newborn intensive care units impact health outcomes in infants, families, and/or staff? We employed a structured review process, resulting in four studies involving the use of color in NICUs. The search was expanded to include general research on responses to color and studies in other healthcare settings. The literature clustered around preferences and psychobiological impact of color on infants and adults in NICUs, the interaction of color and light, and the impact of color on adults in general medical settings. Recommendations are made regarding the importance of modifiability and flexibility in the use of color in NICUs and colors that are associated with stress reduction and stimulation.

Color and NICU Design.

PURPOSE: The appropriate use of color in healthcare settings has been a topic of interest for designers and researchers, and the need for evidence-based standards evident. The purpose of this article is to summarize recent research on color as applicable to neonatal intensive care units and to propose standards for color in these settings. BACKGROUND: Research on this topic is limited due to difficulties associated with constructing research protocols, challenges in setting parameters for the independent variable (color), and the need to simultaneously address infants, families, and caregivers. METHODS: For our literature review, the following research question was developed: Does the use of color in the design of the neonatal intensive care units (NICUs) impact health outcomes in newborn infants, families, and/or staff? Using Arksey and O'Malley's framework for conducting a structured literature review, we (1) identified the research question, (2) identified relevant studies, (3) selected studies, and (4) collated and summarized the results. Only four papers were found regarding NICUs, so the search was expanded to include related healthcare and authors reporting on best practice. RESULTS: Overall, the primary research focused on behavioral or physiological outcomes including the role of wayfinding and art, the impact of lighting on color, and tools for evaluating the impact of color. Best practice recommendations sometimes reflected the primary research but occasionally provided contradictory advice. CONCLUSIONS: Based on the reviewed literature, five topics are addressed: palette malleability; the use of the primary colors, blue, red, and yellow; and the relationship between light and color.

Shifts in Asthma Evaluation and Management During COVID-19.

Purpose of Review: The comprehensive management of asthma has historically relied on in-person visits to obtain a detailed history, thorough physical exam, and diagnostic and monitoring tools such as pulmonary function testing. The COVID-19 pandemic has posed numerous challenges to adequately utilizing these strategies. Despite these limitations, telemedicine has provided an important means to deliver asthma care. In this review, we discuss how these challenges have created paradigm shifts in not only the clinical aspects of asthma management, but also in patient attitudes and physician-patient relationships. Recent Findings: Different strategies have been suggested to address asthma during COVID-19. Telemedicine has taken on an important role during the pandemic. The emphasis on asthma questionnaire use, education regarding lapsed asthma control, and as-needed oral corticosteroid courses have proven to be important instruments in the remote management of asthma. Overall, asthma exacerbations have decreased during this time. This is thought to be due to a variety of factors such as decreased exposure to common triggers. Summary: Although the COVID-19 pandemic significantly limited an allergist's ability to provide conventional comprehensive asthma management, we also found that patient outcomes have actually improved. In addition to the decreased exposure to asthma triggers, this may also be an effect of increased patient ownership of their asthma, and subsequent improved therapeutic alliance.

Pregnancy outcomes following periconceptional or gestational exposure to ustekinumab: Review of cases reported to the manufacturer's global safety database.

BACKGROUND: Ustekinumab, a human immunoglobulin G1 monoclonal antibody that binds to and inhibits interleukin (IL)-12/IL-23, is indicated for multiple immune-mediated diseases. Ustekinumab is actively transported across the placenta and theoretically could impact pregnancy outcomes. Limited data on pregnancy outcomes with ustekinumab exposure are available. AIM: To assess pregnancy outcomes in patients exposed to ustekinumab during pregnancy METHODS: Cumulative data on medically confirmed ustekinumab-exposed pregnancies from the manufacturer's Global Safety Database were summarised. Descriptive data for pregnancy outcomes were presented overall and by patient subgroups. RESULTS: As of 31 August 2020, 408 medically confirmed, prospective, maternal ustekinumab-exposed pregnancies with reported outcomes were identified. The mean maternal age was 31 years. Of the 420 pregnancy outcomes (including 4 sets of twins),a , b 340 (81%) were live births, 51 (12.1%) spontaneous abortions, 25 (6%) elective/induced abortions, 3 (0.7%) stillbirths and 1 (0.2%) ongoing pregnancy with foetal congenital anomaly (CA). Among 340 live births, 33 (9.7%) were born pre-term. The rate of major CAs was similar by indication (Crohn's disease vs psoriasis), ustekinumab dose (45 mg vs 90 mg) and timing and duration of maternal exposure to ustekinumab. Prospective outcomes of pregnancies with paternal periconceptional ustekinumab exposure (n = 87) included 92% live births (1.2% major CA), 5.7% spontaneous abortions and 2.3% elective/induced abortions. CONCLUSIONS: Rates of adverse pregnancy outcomes or CAs with ustekinumab exposure were consistent with rates reported for the US general population and do not suggest a higher risk associated with maternal or paternal exposure to ustekinumab.

The role of keratinocyte growth factor in melanogenesis: a possible mechanism for the initiation of solar lentigines.

Solar lentigines (SLs) are hyperpigmentary lesions presented on sun-exposed areas of the skin and associated with ageing. The molecular mechanism of SL initiation is not completely understood. Ultraviolet B (UVB) stimulates keratinocytes to produce interlukin-1 alpha (IL-1α), which then induces keratinocyte growth factor (KGF) secretion; therefore, we examined their possible roles in the induction of SLs. We found that KGF increases pigment production in both pigmented epidermal equivalents and human skin explants. In addition, UVB exposure increases KGF expression, and KGF treatment induces tyrosinase (TYR) expression in primary melanocytes. The KGF-induced pigmentary changes were confirmed using pigmented Yucatan swine, and human skins grafted onto immuno-deficient mice. In both model systems, the topical treatment with KGF, alone or in combination with IL-1α, resulted in the in vivo formation of hyperpigmentary lesions with increased pigment deposition and elongated rete ridges, which resemble the histological features of human SLs. Preliminary immunohistochemical analysis of human skins showed a moderate increase in KGF, and a strong induction in KGF receptor (KGFR) in SL lesions. In summary, KGF increases pigment production and deposition in vitro and in vivo. Moreover, we show for the first time the in vivo generation of hyperpigmentary lesions with histological resemblance to human SLs and indicate the involvement of KGF/KGFR in the molecular pathology of human SLs.

Characterizing spinal muscular atrophy with electrical impedance myography.

Electrical impedance myography (EIM) is a non-invasive, painless technique for the evaluation of neuromuscular disease, and here we evaluate its potential application in spinal muscular atrophy (SMA). Twenty-one SMA patients and 18 healthy children underwent EIM of biceps brachii and tibialis anterior using a commercially available impedance device. Hand-held dynamometry and ultrasound assessment of subcutaneous fat thickness were also performed. All EIM parameters differed significantly between both SMA patients and normal subjects and between type 2 and type 3 SMA patients. In addition, EIM had an accuracy level as high as 93% for correctly categorizing patients as type 2 or type 3. Multiple regression analyses confirmed a strong association between EIM and dynamometry. These results confirm that EIM can accurately categorize patients with SMA. Because EIM requires no patient effort and is rapid to apply, it may serve a useful role in future SMA clinical trials.

Trigeminocardiac reflex in pediatric adenotonsillectomy: A report of two cases with literature review.

Trigeminocardiac reflex (TCR) is a physiological response that occurs due to stimulation of the trigeminal nerve, resulting in vagus nerve activation, parasympathetic dysrhythmia, and sympathetic hypotension. The pediatric population is vulnerable to TCR due to higher resting vagal tone, which can result in ischemia and death. This study reports two cases of TCR during adenotonsillectomy. Placement and rapid opening of a Crowe-Davis retractor led to immediate bradycardia and hypotension in two children undergoing adenotonsillectomy, which resolved upon release of the retractor. Early intraoperative recognition of TCR with removal of mechanical stimulation can resolve vital instability without need for chemical intervention. Laryngoscope, 130:803-805, 2020.

Aldo-keto reductase 1C subfamily genes in skin are UV-inducible: possible role in keratinocytes survival.

Please cite this paper as: Aldo-keto reductase 1C subfamily genes in skin are UV-inducible: possible role in keratinocytes survival. Experimental Dermatology 2009; 18: 611-618.Abstract: Human skin is endowed with the capacity to synthesize and metabolize steroid hormones, a function of importance in skin physiology and pathology. It is the hormone-regulatory enzymes, including the aldo-keto reductase 1C subfamily (AKR1Cs) that are largely responsible for the local levels of active steroid hormones. AKR1C1 and AKR1C2 inactivate progesterone and 5alpha-dihydrotestosterone, respectively, whereas AKR1C3 activates oestradiol and testosterone. Here, we show that AKR1C1-3 are expressed in keratinocytes and fibroblasts, with marginal expression in melanocytes. In human primary keratinocytes, AKR1C1 and -2 were UVB-inducible in a dose-dependent manner, as shown by quantitative PCR and Western blot analyses. The induction of AKR1C1 by UVB was concomitant with the presence of an apoptotic marker, the cleavage product of poly-ADP ribose polymerase. Similarly, the activation of AKR1C1 and -2 upon UVB exposure was demonstrated in swine skin in vivo and in human skin explants. As expected, hydrogen peroxide-derived reactive oxygen species also induced AKR1C1 and -2 mRNA and protein levels in keratinocytes in a dose-dependent manner. Furthermore, down-regulation of AKR1Cs by small interfering ribonucleic acid led to significantly reduced cell viability. Based on the combined evidence of the presence of an apoptotic marker in the UVB-exposed keratinocytes with increased AKR1Cs expression and reduced cell viability in down-regulated AKR1Cs, we suggest that AKR1C subfamily genes are stress-inducible and might function as survival factors in keratinocytes.

Electrical impedance myography in the assessment of disuse atrophy.

UNLABELLED: Tarulli AW, Duggal N, Esper GJ, Garmirian LP, Fogerson PM, Lin CH, Rutkove SB. Electrical impedance myography in the assessment of disuse atrophy. OBJECTIVE: To quantify disuse atrophy using electrical impedance myography (EIM), a noninvasive technique that we have used successfully to study neurogenic and myopathic atrophy. DESIGN: We performed EIM of the tibialis anterior of subjects with disuse atrophy secondary to cast immobilization and in their contralateral normal leg. Subjects were studied shortly after cast removal and again several weeks to months after the cast was removed and normal mobility was restored. SETTING: Outpatient neurology and orthopedic practices at a tertiary care medical center. PARTICIPANTS: Otherwise healthy subjects (N=10) with unilateral leg fracture. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Resistance, reactance, and phase measured at 50kHz. RESULTS: The main EIM outcome parameter, phase at 50kHz, was lower in the immobilized leg in 9 of 10 cases. Additionally, when normal mobility was restored, the phase of the casted leg increased relative to its initial measurement in all 10 cases, while it increased inconsistently in the contralateral leg. CONCLUSIONS: EIM may be a powerful tool for the assessment of disuse atrophy.

A series of in vitro and human studies of a novel lip cream formulation for protecting against environmental triggers of recurrent herpes labialis.

PURPOSE: These studies describe the testing of a novel, daily-use lip cream designed for individuals with lips prone to recurrent herpes labialis (RHL) that protects against environmental triggers. SUBJECTS AND METHODS: In vitro occlusive and in vitro and in vivo photoprotection analyses, a characterization of normal vs dry lips, and a randomized, evaluator-blinded, clinical trial that assessed the lip cream in healthy subjects with dry lips were conducted. In the clinical trial, subjects applied the lip cream or were untreated and evaluated using transepidermal water loss (TEWL), corneometry, visual assessments of lip dryness, expert photographic evaluations, and subject-rated outcomes. RESULTS: The lip cream's in vitro water vapor transmission rate (84.1 g/(m2 h)) indicated moderate occlusivity. The lip cream, but not placebo or control (water), reduced ultraviolet A (UVA)- and UVB-induced DNA damage, and tumor necrosis factor-α (EpiDermFT) and pros-taglandin E2 release (EpiDermFT and EpiGingival™). The lip cream's in vivo sun protection factor (SPF) was 12.2 (lower confidence limit, 11.3) and SPF/UVA protection factor ratio was 0.9. The characterization of dry vs normal lips identified differences in moisturization. In the clinical trial, the lip cream significantly decreased TEWL (difference: -7.19 [95% CI: -11.41, -2.98]; P<0.01), increased corneometry (difference: 4.62 [95% CI: 1.05, 8.19]; P<0.05), and reduced visual dryness (difference: -1.48 [95% CI: 2.24, -0.71]; P<0.001) compared to untreated subjects. Significant benefits were also observed on expert photographic assessments of scaling (difference: -0.89 [95% CI: -1.75, -0.03]; P< 0.05), cupping (difference: -1.50 [95% CI: -2.30, -0.70]; P<0.001), and healthy appearance (difference: -1.44 [95% CI: -2.29, -0.58]; P<0.01); differences in overall healthy appearance were not significant (P=0.51). Subject-rated assessments indicated improvements in cracking, dryness, and flaking in the lip cream group but worsening in untreated subjects. CONCLUSION: These studies indicate that this novel, daily-use lip cream protects against UV radiation, drying, and chapping, which are established environmental RHL triggers.

Potential therapeutic effect of curcumin, a natural mTOR inhibitor, in tuberous sclerosis complex.

BACKGROUND: Curcumin is a polyphenol natural product of the plant Curcuma longa. Recent studies suggest that curcumin inhibit mTOR activity in vitro, which prompts us to investigate curcumin function as a new class of mTOR inhibitor suitable for tuberous sclerosis complex (TSC) treatment. PURPOSE: We aim to investigate the efficacy of curcumin in the treatment of TSC related manifestations in animal model. STUDY DESIGN: Solid lipid curcumin particle (SLCP), a novel curcumin formulation, was used to treat TSC related manifestations in Tsc2 knockout mice. METHODS: The novel object recognition test was used to analyze the recognition memory function. The long-term potentiation was studied using electrophysiological analysis. Western blotting was used to assess the protein expression and activation status. RESULTS: Recognition memory deficit began as early as 4 weeks of age in both male and female Tsc2+/- mice. Oral administration with SLCP activates AMPK activity and inhibits mTOR activity in the brain tissue of Tsc2+/- mice, and can rescue the electrophysiological abnormality and object recognition memory loss in the mice. CONCLUSIONS: Our results suggest that SLCP could be an effective treatment for TSC patients.

Nondenatured soy extracts reduce UVB-induced skin damage via multiple mechanisms.

UV irradiation results in DNA damage, inflammation and immunosuppression, leading to the development of basal and squamous cell carcinomas. Earlier data show that topical treatment with nondenatured soy extracts reduced the incidence and delayed the development/progression of already-initiated skin tumors in high-risk hairless mice. Here we show that pretreatment with nondenatured soy extracts reduced UVB-induced Thymine-Thymine (TT) dimer formation. In vitro, nondenatured soy extracts enhanced UVB-induced checkpoint kinase-1 (Chk1) activation, suggesting a delay in cell cycle progression that enables longer time for DNA repair. Soy also reduced UVB-induced cyclo-oxygenase-2 (COX-2) expression and prostaglandin E2 secretion, and inhibited p38 MAP kinase activation, suggesting its anti-inflammatory activity. Mice pretreated topically with nondenatured soy extracts had reduced levels of UVB-induced TT dimers and COX-2 expression in their skins compared to UVB alone. The nondenatured soy extracts also inhibited vascular endothelial growth factor-induced endothelial tube formation in Matrigel, suggesting a possible inhibitory effect on angiogenesis and tumor progression. Taken together, nondenatured soy extracts could prevent or reduce UVB-induced skin damage via multiple mechanisms, affecting both the initiation and the progression of skin cancer. These data suggest that topical application of nondenatured soy extracts could potentially reduce the incidence of skin cancer.

Causes and Predictors of Early Hospital Readmission in Systemic Lupus Erythematosus.

OBJECTIVE: We investigated characteristics of adult patients with systemic lupus erythematosus (SLE) readmitted to the hospital within 30 days of discharge, in an attempt to identify the causes of early readmission. METHODS: We performed a retrospective case-control study examining all inpatient electronic health records of patients with SLE at Cedars-Sinai Medical Center over a 2.5-year period (2012-2014). Patients were included if they had an International Classification of Diseases, 9th ed diagnosis of SLE and were readmitted within 30 days of their initial hospitalization. Patients with SLE not readmitted during this time period were used as a control group. Demographic and clinical variables for each patient were collected, and we used the Charlson Comorbidity Index to characterize comorbidities. The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was used to assess the chronic damage of SLE. Stepwise multivariable logistic regression analysis was used to predict factors associated with readmission. RESULTS: In total, 570 hospitalizations representing 455 unique patients met our inclusion and exclusion criteria. Of these, 154 patients (34%) underwent readmission within 30 days of their initial hospitalization. Patients in the early readmission group were more likely to have government-sponsored Medicaid insurance and were significantly associated with an increased SDI (OR 1.27, 95% CI 1.1-1.48), lower serum hemoglobin (OR 0.82, 95% CI 0.72-0.93), and lower serum albumin (OR 0.66, 95% CI 0.47-0.91). CONCLUSION: One-third of hospitalized patients with SLE were readmitted within 30 days at our institution. We identified characteristics of this at-risk population at time of discharge with high specificity, in hopes of reducing this costly outcome.