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Background: Peri-operative separation anxiety in children adversely impacts on their cognitive function and behavioural outcome. The aim of the study was to assess the effect of two different doses of oral midazolam premedication on separation anxiety in paediatric patients scheduled for herniotomy. Methods: Eighty-four eligible children aged 1-6 years, of American Society of Anesthesiologists (ASA) class I or II, scheduled for herniotomy, were randomized into two groups, A and B, of 42 each after ethical clearance and written parental consent. Children in group A and group B received 0.5 mg/kg and 0.75 mg/kg respectively of oral midazolam flavoured with paracetamol syrup, were observed, and later separated from parents at 30 min post-premedication. Premedicant acceptability was noted, and separation anxiety was assessed using the Richmond agitation sedation scale (RASS). Statistical significance was set at p0.05. Conclusions: Oral 0.5 mg/kg and 0.75 mg/kg midazolam induced desirable sedation in children at the 30th min with comparable lower agitation scores; however, the 0.75 mg/kg dose achieved significantly faster onset and higher level of sedation in a greater proportion of the subjects.

During pandemics, individuals exhibit differences in risk and clinical outcomes. Here, we developed single-cell high-throughput human

Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or who experience breakthrough infections. Understanding the common host factors necessary for the life cycles of coronaviruses may reveal conserved therapeutic targets. Here, we used the known substrate specificities of mammalian protein kinases to deconvolute the sequence of phosphorylation events mediated by three host protein kinase families (SRPK, GSK-3, and CK1) that coordinately phosphorylate a cluster of serine and threonine residues in the viral N protein, which is required for viral replication. We also showed that loss or inhibition of SRPK1/2, which we propose initiates the N protein phosphorylation cascade, compromised the viral replication cycle. Because these phosphorylation sites are highly conserved across coronaviruses, inhibitors of these protein kinases not only may have therapeutic potential against COVID-19 but also may be broadly useful against coronavirus-mediated diseases.

Vaccines targeting SARS-CoV-2 have been shown to be highly effective; however, the breadth against emerging variants and the longevity of protection remains unclear. Postimmunization boosting has been shown to be beneficial for disease protection, and as new variants continue to emerge, periodic (and perhaps annual) vaccination will likely be recommended. New seasonal influenza virus vaccines currently need to be developed every year due to continual antigenic drift, an undertaking made possible by a robust global vaccine production and distribution infrastructure. To create a seasonal combination vaccine targeting both influenza viruses and SARS-CoV-2 that is also amenable to frequent reformulation, we have developed an influenza A virus (IAV) genetic platform that allows the incorporation of an immunogenic domain of the SARS-CoV-2 spike (S) protein onto IAV particles. Vaccination with this combination vaccine elicited neutralizing antibodies and provided protection from lethal challenge with both pathogens in mice. This approach may allow the leveraging of established influenza vaccine infrastructure to generate a cost-effective and scalable seasonal vaccine solution for both influenza and coronaviruses.

Sheet metal bending manufacturing companies require changeable and adaptable process planning systems to shorten the production cycle time and reduce operations costs. This is due to globalisation ...

BACKGROUND: A systematic review of the literature uncovered little explanation as to why academics as individuals switch mobile applications or continue to use the same mobile applications. Knowing and being able to explain the personal behaviour are important and could be of value to practitioners and researchers, especially when it comes to predicting the future behaviour OBJECTIVES: The main objective of this study was to explain and to model switching and continued use of mobile computing applications by South African academics METHOD: A survey was carried out within South African academics as participants to test 14 hypotheses and explain switching and continued use of mobile computing applications. The adopted positivist study was associated with the quantitative research approach to test hypotheses so that the truth about objectives are obtainable RESULTS: The results of the study contributed to the body of knowledge by explaining and modelling the determinants influencing and significant to mobile computing application switching and continued use behaviour CONCLUSION: The developed model may help to inform practitioners and researchers on what actually satisfies users to switch or continue to use mobile computing applications

GPER1 in utero to the rescue! Several common pathogens, including influenza A virus (IAV), can activate systemic type I interferon (IFN) signaling during pregnancy. Such infections would be expected to cause birth defects and fetal mortality, but maternal IAV infections rarely produce such effects, suggesting the presence of a protective mechanism in fetal tissues. Harding et al. used a CRISPR screen to uncover IFN regulators that can mediate differential IFN control across tissues in human cell lines. They found that G protein–coupled estrogen receptor 1 (GPER1), which is expressed in fetal tissues, acts as a protective suppressor of IFN responses in the placenta during maternal infection. In a mouse model, pharmacological activation of GPER1 shielded fetuses from maternal inflammation. Activation of GPER1 might be promising therapeutically to protect the fetus from both maternal and fetal infections. Science , this issue p. 271

In this population-based, cross-sectional study of Indian and Malay adults in Singapore aged 40 years or above, intermediate or high risk of obstructive sleep apnea (OSA) was associated with 50% higher odds of having glaucoma.The relationship between OSA and glaucoma is unclear. We assessed the association between the risk of OSA and glaucoma in an Asian population.In this population-based, cross-sectional study, we included Indian and Malay adults aged 40 years or above recruited between 2011 and 2015. Glaucoma was assessed by trained ophthalmologists and classified into primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG). OSA risk was assessed with the Snoring, Tiredness, Observed apnea, High blood pressure, Body mass index, Age, Neck circumference, and male Gender (STOP-Bang) questionnaire and categorized as low risk (3) or intermediate/higher risk (≥3). We used multivariable logistic regression models to evaluate the relationship between risk of OSA and glaucoma adjusted for key variables, and further stratified for subtype and ethnicity.Of the 3126 participants (mean age: 63.1±9.6 y; 52.5% female), 134 (4.3%) had glaucoma, comprising 86 (2.8%) POAG, 22 (0.7%) PACG and 26 (0.8%) secondary glaucomas, and 1182 (37.8%) had an intermediate/higher risk of OSA. Compared with individuals with a low risk of OSA, individuals with intermediate/higher risk had 50% greater odds of having glaucoma (odds ratio: 1.55, 95% confidence interval: 1.03-2.33; P =0.035). We observed a nonsignificant increase in likelihood of having POAG in those with intermediate/higher risk of OSA compared with those with low risk. The OSA-glaucoma relationship was modified by ethnicity, with Malays with intermediate/higher risk of OSA having a 2-fold risk of having any glaucoma (odds ratio: 2.01, 95% confidence interval: 1.12-3.59 P =0.019); while the same elevated risk was not observed for Indians.Intermediate or high risk of OSA is associated with 50% higher odds of having glaucoma in our Singaporean population, with a 2-fold higher risk of glaucoma observed in Malays (but not Indians); however a conformational sleep study is needed.

Introduction:Metformin is an antihyperglycemic medication most commonly used to treat Type II Diabetes Mellitus with promising off-label application for the treatment of hidradenitis suppurativa, psoriasis, acne, acanthosis nigricans, and hirsutism. Objective: To comprehensively assess evidence regarding the use of metformin for treating primary cutaneous disorders. Materials and Methods: A systematic literature search was conducted through PubMed, Cochrane, Web of Science, and CINAHL to identify the role of metformin in primary skin disease. Results: Sixty-four studies met inclusion criteria. Metformin demonstrates promising clinical response and favorable safety profile for treatment of HS, with most patients experiencing a decrease in frequency or severity of HS flares, and some experiencing full resolution of HS lesions. Patients with psoriasis treated with metformin experienced quantifiable clinical responses. Application of metformin on polycystic ovarian disease (PCOS) related acne, acanthosis nigricans, and hirsutism yielded mixed clinical results. No serious adverse effects were reported. Conclusion: Metformin is safe and efficacious and may be considered as an adjunctive therapy for the treatment of psoriasis and hidradenitis suppurativa in addition to first line therapies as well as PCOS related acne, acanthosis nigricans, and hirsutism. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.4874.

Background Injectable deoxycholic acid (DCA) may be used to remove excess submental fat and off-label for local adipose reduction. Despite DCA's widespread use, rare incidences of severe, systemic, long-term adverse events (AEs) have been reported. Objective To evaluate the potential side effects associated with injectable DCA. Methods and materials A systematic review was conducted using PubMed, Cochrane, CINAHL, and Web of Science using PRISMA guidelines to gather the literature relating to DCA or deoxycholate-associated AEs and their management. Results Twenty-eight manuscripts were included after full article review. Most commonly, patients experienced mild localized AEs, whereas a small number of patients experienced severe pain, alopecia, nasopharyngitis, dysphagia, dizziness/lightheadedness, and gastrointestinal upset. Severe, long-term AEs were reported as rare in the evaluated literature. Deoxycholic acid injections in large volumes were more likely to cause severe adverse effects. Conclusion Self-resolving, mild side effects and severe but rare adverse effects have been reported with DCA use making it a safe treatment for local adipose reduction. Further studies are necessary to determine its safety profile, especially when using DCA in off-label areas.

SummaryDiversity in the human genome is one factor that confers resistance and susceptibility to infectious diseases. This is observed most dramatically during pandemics, where individuals exhibit large differences in risk and clinical outcomes against a pathogen infecting large portions of the world’s populations. Here, we developed scHi-HOST (single cell High-throughput Human in vitrO Susceptibility Testing), a method for rapidly identifying genetic variants that confer resistance and susceptibility to pathogens. scHi-HOST leverages scRNA-seq (single-cell RNA-sequencing) to simultaneously assign genetic identity to individual cells in mixed infections of cell lines of European, African, and Asian origin, reveal associated genetic variants for viral entry and replication, and identify expression quantitative trait loci (eQTLs). Applying scHi-HOST to influenza A virus (IAV), we identified eQTLs at baseline and in genes that are induced by IAV infection. Integration of scHi-HOST with a human IAV challenge study (Prometheus) revealed that a missense variant inERAP1(Endoplasmic reticulum aminopeptidase 1;rs27895) was associated with IAV burden in cells and human volunteers. Functional studies using RNA interference, ERAP1 inhibitor, and overexpression of alternative alleles demonstrated that ERAP1 is exploited by IAV to promote infection. Specifically, the nonsynonymous substitution, which results in a glycine to aspartate substitution at ERAP1 residue 348, would disrupt the substrate binding pocket of ERAP1, likely resulting in a significantly altered preference for substrates, poorer catalytic efficiency, or both. Finally, rs27895 exhibits substantial population differentiation, with the higher frequency of the minor T allele in two African populations likely contributing to the greater permissivity of cells from these populations to IAV infection. scHi-HOST is an important resource for understanding susceptibility to influenza and is a broadly applicable method for decoding human genetics of infectious disease.

Background: Post adenotonsillectomy coughing and laryngospasm in children entails deleterious sequelae, warranting continued search for effective prophylaxis. The aim was to determine the prophylactic efficacy of intravenous mini-dose (0.1 mg/kg) suxamethonium, 1.5 mg/kg lidocaine 1%, and their combination, against coughing and laryngospasm in children emerging from general anaesthesia after adenotonsillectomy.Methods: Ethical approval and parental written consent secured, 69 children, aged 1-6 years, of American Society of Anesthesiologists (ASA) class I were randomized into groups A, B, and C, of 23 each. All patients had general anaesthesia induced with propofol 2 mg/kg plus fentanyl 2 µ/kg, maintained with isoflurane 1-1.5% in 100% oxygen, and tracheal intubation facilitated by pancuronium 0.075 mg/kg. Two minutes after reversal dose of neostigmine, groups A, B and C respectively received 1.5 mg/kg lidocaine 1%, suxamethonium 0.1 mg/kg, and 1.5 mg/kg lidocaine 1% plus suxamethonium 0.1 mg/kg, intravenously. Tracheal extubation was done 90 seconds after study drug administration, and coughing and laryngospasm were assessed for 10 minutes using modified Minogue and Likert 4-point scales respectively.Results: All 69 subjects completed the study. The incidence of mild to moderate coughing was 22 (95.7%) in groups A and B, and 19 (82.6%) in group C, p=1.000. Laryngospasm occurred in none (0.0%) in group C, while in groups A and B its occurrence was 1(4.3%), p=1.000.Conclusions: Mini-dose suxamethonium or lidocaine 1.5 mg/kg prevented grade 3 coughing and laryngospasm; furthermore, their combination prevented grade 3 coughing and achieved zero incidence of laryngospasm.

Background: There is continued search for an ideal adjuvant necessitated by the limited duration of singleshot caudal block. The study aimed to compare the analgesic effects of caudal 1.5 µg/kg dexmedetomidine versus 50 µg/kg midazolam combined with 0.20% bupivacaine in children.Methods: Following ethical approval and parental consent, 66 American Society of Anesthesiologists (ASA) class I or II children aged 1-6 years were randomized into three groups (A, B, and C) of 22 each. All patients had laryngeal mask airway (LMA) general anaesthesia induced with propofol and maintained with isoflurane in 100% oxygen. Group A received 1 ml/kg 0.20% bupivacaine and 1.5 µg/kg dexmedetomidine (1 ml), B received 1 ml/kg 0.20% bupivacaine plus 50 µg/kg midazolam (1 ml) while C received 1 ml/kg 0.20% bupivacaine and 0.9% normal saline (1 ml), via the caudal space. Pain was assessed using the face, leg, arm, cry, consolability (FLACC) scale. The time to first analgesic request, (TTFAR) was defined as the period from caudal injection to pain score of ≥4. Analgesic was given when FLACC score was ≥4.Results: All 66 children completed the study. The TTFAR was longest in group A (14.4±2.36), followed by group B (12.0±3.69), and shortest in group C (5.6±1.45), p=0.01, with greatest 24 hours analgesic consumption in group C, p=0.01.Conclusions: Caudal dexmedetomidine or midazolam combined with bupivacaine significantly prolonged the analgesic duration, with superiority of dexmedetomidine over midazolam group in analgesic profile.

The diagnosis of epilepsy is primarily based on the history and the verbal description of the events in question. Smartphone videos are increasingly used to assist in the diagnosis. The purpose of this study is to evaluate their value for the diagnosis of seizures. We prospectively collected smartphone videos from patients who presented to our epilepsy center over two years. The video-based diagnosis was then compared to the eventual diagnosis based on video-electroencephalographic (EEG) monitoring with recorded episodes. Video-EEG studies and smartphone videos were reviewed by two separate physicians, each blinded to the other's interpretation. Fifty-four patients were included in the final analysis (mean age = 34.7 years, SD = 17 years). Data (either smartphone video or video-EEG monitoring) were inconclusive in 18 patients. Of the 36 patients with conclusive data, 34 (94%) were in agreement. Smartphone video interpretation can be a useful adjunctive tool in the diagnosis of seizure-like events.

The type I interferon (IFN) response is an important component of the innate immune response to viral infection. Precise control of IFN responses is critical because insufficient expression of IFN-stimulated genes (ISGs) can lead to a failure to restrict viral spread, whereas excessive ISG activation can result in IFN-related pathologies. Although both positive and negative regulatory factors control the magnitude and duration of IFN signaling, it is also appreciated that several ISGs regulate aspects of the IFN response themselves. In this study, we performed a CRISPR activation screen to identify previously unknown regulators of the type I IFN response. We identified the strongly induced ISG encoding ETS variant transcription factor 7 (ETV7) as a negative regulator of the type I IFN response. However, ETV7 did not uniformly suppress ISG transcription. Instead, ETV7 preferentially targeted a subset of antiviral ISGs that were particularly important for IFN-mediated control of influenza viruses. Together, our data assign a function for ETV7 as an IFN response regulator and also identify ETV7 as a potential therapeutic target to increase innate antiviral responses and enhance IFN-based antiviral therapies.

We investigated the ability of Luminore CopperTouch™ copper and copper-nickel surfaces to inactivate filoviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this purpose, we compared viral titers in Vero cells from viral droplets exposed to copper surfaces for 30 min. The copper and copper-nickel surfaces inactivated 99.9% of the viral titer of both Ebola and Marburg viruses. The copper surfaces also inactivated 99% of SARS-CoV-2 titers in 2 hours to close to the limit of detection. These data add Ebolavirus, Marburgvirus, and SARS-CoV-2 (COVID-19) to the list of pathogens that can be inactivated by exposure to copper ions, validating Luminore CopperTouch™ technology (currently the only Environmental Protection Agency [EPA]-registered cold spray antimicrobial surface technology) as an efficacious, cost-friendly tool to improve infection control in hospitals, long-term care facilities, schools, hotels, buses, trains, airports, and other highly trafficked areas.

Vaccines targeting SARS-CoV-2 have gained emergency FDA approval, however the breadth against emerging variants and the longevity of protection remains unknown. Post-immunization boosting may be required, perhaps on an annual basis if the virus becomes an endemic pathogen. Seasonal influenza virus vaccines are already developed every year, an undertaking made possible by a robust global vaccine production and distribution infrastructure. To create a seasonal combination vaccine targeting influenza viruses and SARS-CoV-2 that is also amenable to frequent reformulation, we have developed a recombinant influenza A virus (IAV) genetic platform that “reprograms” the virus to package an immunogenic domain of the SARS-CoV-2 spike (S) protein onto IAV particles. Vaccination with this combination vaccine elicits neutralizing antibodies and provides protection from lethal challenge with both pathogens. This technology may allow for leveraging of established influenza vaccine infrastructure to generate a cost-effective and scalable seasonal vaccine solution for both influenza and coronaviruses.

At the Fermilab Tevatron proton-antiproton ($p\bar{p}$) collider, high-mass electron-neutrino ($e\nu$) pairs are produced predominantly in the process $p \bar{p} \rightarrow W(\rightarrow e\nu) + X$. The asymmetry of the electron and positron yield as a function of their pseudorapidity constrain the slope of the ratio of the $u$- to $d$-quark parton distributions versus the fraction of the proton momentum carried by the quarks. This paper reports on the measurement of the electron-charge asymmetry using the full data set recorded by the Collider Detector at Fermilab in 2001--2011 and corresponding to 9.1~fb$^{-1}$ of integrated luminosity. The measurement significantly improves the precision of the Tevatron constraints on the parton-distribution functions of the proton. Numerical tables of the measurement are provided., Comment: 27 pages, 25 figures. To be published in PRD

IntroductionAs childhood mortality from infectious diseases falls across sub-Saharan Africa (SSA), the burden of disease attributed to surgical conditions is increasing. However, limited data exist on paediatric surgical outcomes in SSA. We compared the outcomes of five common paediatric surgical conditions in SSA with published benchmark data from high-income countries (HICs).MethodsA multicentre, international, prospective cohort study was undertaken in hospitals providing paediatric surgical care across SSA. Data were collected on consecutive children (birth to 16 years), presenting with gastroschisis, anorectal malformation, intussusception, appendicitis or inguinal hernia, over a minimum of 1 month, between October 2016 and April 2017. Participating hospitals completed a survey on their resources available for paediatric surgery.The primary outcome was all-cause in-hospital mortality. Mortality in SSA was compared with published benchmark mortality in HICs using χ2 analysis. Generalised linear mixed models were used to identify patient-level and hospital-level factors affecting mortality. A pResults1407 children from 51 hospitals in 19 countries across SSA were studied: 111 with gastroschisis, 188 anorectal malformation, 225 intussusception, 250 appendicitis and 633 inguinal hernia. Mortality was significantly higher in SSA compared with HICs for all conditions: gastroschisis (75.5% vs 2.0%), anorectal malformation (11.2% vs 2.9%), intussusception (9.4% vs 0.2%), appendicitis (0.4% vs 0.0%) and inguinal hernia (0.2% vs 0.0%), respectively. Mortality was 41.9% (112/267) among neonates, 5.0% (20/403) in infants and 1.0% (7/720) in children. Paediatric surgical condition, higher American Society of Anesthesiologists score at primary intervention, and needing/receiving a blood transfusion were significantly associated with mortality on multivariable analysis.ConclusionMortality from common paediatric surgical conditions is unacceptably high in SSA compared with HICs, particularly for neonates. Interventions to reduce mortality should focus on improving resuscitation and timely transfer at the district level, and preoperative resuscitation and perioperative care at paediatric surgical centres.

The application of enhanced recovery after surgery (ERAS) has the potential to improve outcomes, hasten patient recovery, and reduce costs. ERAS has been applied to spine surgery for several years, but data are limited around the impact of ERAS on minimally invasive spine surgery, specifically. The authors report their experience implementing a multimodal ERAS protocol for patients receiving minimally invasive transforaminal lumbar interbody fusion.The ERAS protocol was implemented at The Valley Hospital Hospital in Ridgewood, New Jersey in January 2020. Following implementation, all patients receiving minimally invasive transforaminal lumbar interbody fusion by a single surgeon were studied. The authors analyze the impact of the protocol on length of stay (LOS), disposition post discharge, and opioid consumption postoperatively in the inpatient and outpatient settings.Sixteen patients were enrolled in the protocol and compared with 17 historical controls. LOS was significantly shorter in the ERAS cohort (1.6 vs. 2.4 days,ERAS application to minimally invasive transforaminal lumbar interbody fusion was safe and effective, significantly reducing LOS and inpatient opioid consumption. These data reflect the importance of uniformly applying a multimodal ERAS protocol to accelerate recovery and reduce narcotic use.

Background: When spinal analgesia is used for relief of labour pain, a major challenge has been how to extend its duration without increasing the associated adverse effects. The aim of this study was to evaluate the effect of intra-thecal midazolam on pain relief by low dose bupivacaine and morphine mixture administered intrathecally to women in labour.Methods: 160 labouring women, aged between 18 and 40 years gave consent and enrolled for this comparative study. The women were randomly allocated into two equal groups, MBM and BM. Group MBM received intrathecal 2.0 mg midazolam, 2.5 mg bupivacaine and 150 mcg morphine. Group BM received intra-thecal 2.5 mg bupivacaine and 150 mcg morphine. An epidural bolus dose of bupivacaine 10 mg plus fentanyl 25 mcg was given whenever rescue analgesia was needed. Foeto-maternal parameters, were assessed and recorded.Results: Duration of effective spinal analgesia was significantly longer in group MBM than in group BM, p=0.0001. More participants in group BM had epidural rescue analgesia compared to group MBM, p=0.001. More participants in group MBM had adequate spinal analgesia till delivery compared to group BM, p=0.001. All the participants in both groups were able to ambulate without support after 30 minutes following the injection of spinal drugs. Nausea and vomiting occurred less commonly in group MBM than in BM, p=0.006.Conclusions: Addition of midazolam to bupivacaine-morphine co-mixture significantly prolonged the duration of spinal analgesia without affecting ambulation or causing any considerable maternal or neonatal adverse effect.

We investigated the ability of Luminore CopperTouch™ copper and copper-nickel surfaces to inactivate filoviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this purpose, we compared viral titers in Vero cells from viral droplets exposed to copper surfaces for 30 min. The copper and copper–nickel surfaces inactivated 99.9% of the viral titer of both Ebola and Marburg viruses. The copper surfaces also inactivated 99% of SARS-CoV-2 titers in 2 hours to close to the limit of detection. These data add Ebolavirus, Marburgvirus, and SARS-CoV-2 (COVID-19) to the list of pathogens that can be inactivated by exposure to copper ions, validating Luminore CopperTouch™ technology (currently the only Environmental Protection Agency-registered cold spray antimicrobial surface technology) as an efficacious, cost-friendly tool to improve infection control in hospitals, long-term care facilities, schools, hotels, buses, trains, airports, and other highly trafficked areas.

Swift identification of hemiballismus as a complication of poorly controlled type 2 diabetes mellitus may help facilitate optimal care through glycemic control and prevent debilitating loss of patients' function and autonomy, prolonged hospital stays, and overuse of resources.

Background: There has been continuous debate among scholars regarding fertility transition in Africa. Two conclusions emerge: slow pace of decline because of weak facilitating social programs and high demand for large families amidst weak family planning programs. Accelerated fertility decline is expected to occur if there is both substantial decline in desired fertility and increased level of preference implementation. Despite these conclusions, there are also emergent exceptions in Africa, even among the Eastern African countries. Our motivation for the study of this region therefore lies in this context. First, the East African countries share some similarities in policy framework. Secondly, Rwanda and Kenya appear as exceptional in the drive towards accelerating further fertility decline. Fertility change therefore in any one country may have implications in the neighbouring country due to the commonalities especially in language, cultural traits, diffusion and spread new models of behaviour. Methods: With the utilization of DHS data, we analyse trends overtime in two specific features that scholars have indicated to slow or increase fertility decline. Using Bongaarts supply-demand framework, we first deduce trends in fertility preferences among women of reproductive age (15-49 years) and second, the extent to which women have been able to implement their fertility preferences during the course of fertility decline and subsequently decomposing these trends. Results: We found that with the rising aggregate of the degree of fertility preference implementation index, continuous declining trends in demand for births and subsequent increases in the contribution made by either or both the wanted fertility and the degree of fertility preference implementation index across categories that fertility transition is certainly on course in all countries albeit at different levels, thanks to the family planning. Conclusions: Family planning programs must therefore be accompanied by rigorous, consistent sensitization and public education.

Objectives To compare prevalence and severity of diaper dermatitis (DD) in infants and toddlers (babies) across three countries (China, USA, and Germany), including diapered skin measures and caregiver practices. Methods A cross‐sectional study of 1791 babies (~600 from each country) was recruited at each clinical site. Based on regional toilet‐training habits, exclusively diaper‐wearing infants were recruited between ages 2‐8 months in China and 2‐18 months in the USA and Germany. DD was measured, as well as skin pH, transepidermal water loss (TEWL), and relative humidity (RH) in the diapered region. Caregiver habits were collected via a questionnaire and included information on hygienic practices. Results Diaper dermatitis was highest in the perianal area, followed by the intertriginous, genital, and buttock regions. In general, DD was significantly lower in babies in China, highest in Germany, and intermediate in the USA. This rank ordering of DD by geography was also observed in baby age 2‐8 months. The lower DD observed in China was associated with lower skin pH and TEWL on diapered skin and decreased RH in the diaper. Chinese caregivers had the highest rate of prophylactic topical product usage, the most robust cleaning of the diapered area, lack of cleansing after urine‐only diaper changes, and Chinese infants spent the least time in an overnight diaper. Conclusions These data suggest caregiver behaviors including prophylactic use of topical products, thorough cleaning after stooling and reduced time in an overnight diaper are associated with less DD, lower superficial skin pH, and enhanced skin barrier.

The type I interferon (IFN) response is an important component of the innate immune response to viral infection. Precise control of interferon responses is critical; insufficient levels of interferon-stimulated genes (ISGs) can lead to a failure to restrict viral spread while excessive ISG activation can result in interferon-related pathologies. While both positive and negative regulatory factors control the magnitude and duration of IFN signaling, it is also appreciated that a number of ISGs regulate aspects of the interferon response themselves. However, the mechanisms underlying these ISG regulatory networks remain incompletely defined. In this study, we performed a CRISPR activation screen to identify new regulators of the type I IFN response. We identified ETS variant transcription factor 7 (ETV7), a strongly induced ISG, as a protein that acts as a negative regulator of the type I IFN response; however, ETV7 did not uniformly suppress ISG transcription. Instead, ETV7 preferentially targeted a subset of known antiviral ISGs. Further, we showed the subset of ETV7-modulated ISGs was particularly important for IFN-mediated control of some viruses including influenza viruses and SARS-CoV-2. Together, our data assign a function for ETV7 as an IFN response regulator and also identify ETV7 as a therapeutic target to increase innate responses and potentiate the efficacy of interferon-based antiviral therapies.One Sentence SummaryETV7 is an interferon-induced, repressive transcription factor that negatively regulates antiviral interferon-stimulated genes essential for controlling influenza virus and SARS-CoV-2 infections.

Bipolar I disorder and interictal personality syndrome have many overlapping characteristics that are difficult to distinguish. There is scant literature focused on interictal personality syndrome and no case reports to date detailing patients with comorbid bipolar pathology. We describe an individual with a history of bipolar I disorder who developed right temporal lobe epilepsy after several head injuries. He subsequently exhibited symptoms consistent with interictal personality syndrome that were independent of his bipolar symptomatology. Better understanding of these disorders can lead to improved diagnosis and symptom management. The similarities may also point to a partially shared neuropathology.

Background: Since the early 2000s, there has been an extensive debate on whether migration and inequality are interlinked, with varying conclusions arising from methodological as well as theoretical dispositions. The aim of this study is to contribute to this debate by exploring the nexus between several dimensions of inequalities and migration in Kenya. Methods: This study used the subnational(county) data on inequalities and migration in Kenya obtained from several reports. Four explanatory variables including access to water, electricity, composite index of County Human Development Index (County HDI) and County Gini were used. Our dependent variable was migration intensity, measured by the Revised Weighted Net Migration Rate. Correlation and spatial regression analysis were performed to model the relationship between migration and inequality. Results: Findings revealed that migration had a non-linear relationship with income inequality, such that a change in one unit of migration intensity results in a 567 negative change in County Gini. The County Gini had the highest explanatory power in our model, although counties with high HDI tend to have higher migration intensities. Migration intensities in the country were not randomly distributed as we found evidence of spatial clustering with two key emergent hotspots, a high-high in the lake region and a low-low in the coastal region. Regions with low migration intensities correspond with higher poverty, implying that structural factors may explain the migration intensities in the country. Conclusions: The study highlights that the subnational income inequality reduces as migration intensifies. We conclude that migration has an equalizing effect on inequality as observed in some studies. Regions with high poverty tend to have lower migration intensity, implying that structural factors are important in influencing migration. Use of migration intensity and application of spatial analysis have improved our understanding of migration and inequality, and should be applied in future research.

Objective Subependymomas are infrequent, low-grade gliomas associated with the ventricular system and the spinal cord. Little is known about the origin and natural history of these slow-growing lesions. Methods We identified all patients with pathologically proven subependymomas presenting to our institution between 1998 and 2016. We retrospectively reviewed clinical, radiographic, histologic, and surgical outcomes data in all patients who underwent surgical resection. Immunohistochemical analyses for cell lineage markers were performed. Results A total of 31 patients with pathologically proven subependymomas were identified. Of these, 7 asymptomatic lesions were discovered at autopsy and 24 symptomatic cases were treated surgically. There were 15 (48%) lateral ventricle tumors, 11 (35%) fourth ventricular tumors, and 5 (17%) spinal tumors. Symptomatic intracranial lesions most commonly presented with headaches and balance and gait abnormalities. Subependymomas had no distinguishing radiographic features that provided definitive preoperative diagnosis. At last follow-up, no patient treated surgically experienced recurrence. Immunohistochemical analyses demonstrated a diffusely GFAP-positive glial neoplasm with mixed populations of cells that were variably positive for Olig2, NHERF1, Sox2, and CD44. The Ki67 proliferation index was generally low ( Conclusions Subependymomas demonstrate mixed populations of cells expressing glial lineage markers as well as putative stem cell markers, suggesting these tumors may arise from multipotent glial progenitors that reside in the subventricular zone. Definitive diagnosis requires surgical sampling. Although the clinical course of subependymomas appears benign, the inability to radiographically diagnose these lesions, and the possibility of an alternative malignant lesion support a low threshold for early and safe maximal resection.

Influenza A virus (IAV) is a pathogen that poses significant risks to human health. It is therefore critical to develop strategies to prevent influenza disease. Many loss-of-function screens have been performed to identify the host proteins required for viral infection. However, there has been no systematic screen to identify the host factors that when over-expressed are sufficient to prevent infection. In this study, we utilized CRISPR/dCas9 activation technology to perform a genome-wide overexpression screen to identify IAV restriction factors. The major hit from our screen, B4GALNT2, showed inhibitory activity against influenza viruses with an α2,3 linked sialic acid receptor preference. In fact, B4GALNT2 overexpression prevented the infection of every avian influenza virus strain tested, including the H5, H9, and H7 subtypes, which have previously caused disease in humans. Thus, we have utilized CRISPR/dCas9 activation technology to identify a factor that can completely abolish infection by avian influenza viruses.

Study Design: A retrospective, blinded analysis of imaging studies. Summary of Background Data: To evaluate changes in paraspinal muscle cross-sectional area (CSA) after surgical treatment for lumbar stenosis and to compare these changes between minimally invasive and standard open approaches. The open approach to lumbar stenosis is effective, but it involves retraction and resection of muscle from the spinous process, which can result in ischemia and denervation of paraspinal musculature and may lead to muscle atrophy and pain. Objective: It is hypothesized that the microendoscopic decompression of stenosis (MEDS) technique will better preserve the paraspinal muscles compared with the open procedure. Materials and Methods: A total of 18 patients underwent a 1-level posterior decompression for lumbar stenosis, (9 open, 9 MEDS). Lumbar magnetic resonance imaging was obtained before surgery and after surgery (open approach average 16.3 mo; MEDS average 16.6 mo). CSA of paraspinal muscles were averaged over the distance of the surgical site. Results: The mean age of patients treated with the open and MEDS approaches were 55.2 and 66.4 years, respectively (P=0.07). Paraspinal muscle CSA decreased by an average of 5.4% (SD=10.6%; range, −24.5% to +7.7%) in patients treated with the open approach and increased by an average of 9.9% (SD=14.4%; range, −9.8% to +33.1%) in patients treated with MEDS (P=0.02). For the open approach, changes in CSA did not differ significantly between the left and right sides for erector spinae (P=0.35) or multifidus muscles (P=0.90). After the MEDS approach there were no significant differences between the dilated and contralateral sides with regard to change in CSA for erector spinae (P=0.85) or multifidus muscles (P=0.95). Conclusions: Compared with the open approach for lumbar stenosis, MEDS had significantly less negative impact on the paraspinal muscle CSA. Previous reports have documented negative effects of paraspinal muscle injury, including weakness, disability, and pain. Collectively, these data suggest that the MEDS approach for lumbar decompression is less destructive to the paraspinous muscles than the open approach and may facilitate better clinical outcomes.

Pseudobulbar affect (PBA) consists of unprovoked and uncontrollable episodes of laughing and/or crying. In end-of-life situations, PBA symptoms can be especially distressing to family and friends during an already heightened emotional time. Although a commercial product combining dextromethorphan and quinidine (DMQ) is FDA approved for use in PBA, many hospice patients are unable to swallow any solids or semisolids. An alternative formulation for these patients is needed.We present here two cases in which we used a compounded DMQ suspension successfully to treat PBA symptoms in the weeks before the patients' death.A retrospective chart review was completed on the two cases where the DMQ suspension was used. A description of the DMQ suspension formula is described.Both patients were under the care of a hospice program; one in home care and one in a skilled nursing facility.Episodes of PBA symptoms were summarized in a narrative of the patients' symptom relief.Both patients tolerated the administration of the DMQ suspension and there were noted improvements in PBA symptoms.DMQ suspension is an effective alternative for PBA symptoms in patients who cannot swallow oral solid medication.

Identification of epilepsy patients from administrative data in large managed healthcare organizations is a challenging task. The objectives of this report are to describe the implementation of an established algorithm and different modifications for the estimation of epilepsy prevalence in the Veterans Health Administration (VHA). For the prevalence estimation during a given time period patients prescribed anti-epileptic drugs and having seizure diagnoses on clinical encounters were identified. In contrast to the established algorithm, which required inclusion of diagnoses data from the time period of interest only, variants were tested by considering diagnoses data beyond prevalence period for improving sensitivity. One variant excluded data from diagnostic EEG and LTM clinics to improve specificity. Another modification also required documentation of seizures on the problem list (electronic list of patients’ established diagnoses). Of the variants tested, the one excluding information from diagnostic clinics and extending time beyond base period of interest for clinical encounters was determined to be superior. It can be inferred that the number of patients receiving care for epilepsy in the VHA ranges between 74,000 and 87,000. In the wake of the recent implementation of ICD-10 codes in the VHA, minor tweaks are needed for future prevalence estimation due to significant efforts presented. This review is not only beneficial for researchers interested in VHA related data but can also be helpful for managed healthcare organizations involved in epilepsy care aiming at accurate identification of patients from large administrative databases.

The treatment of complex wounds is commonplace for plastic surgeons. Standard management is debridement of infected and devitalized tissue and systemic antibiotic therapy. In cases where vital structures are exposed within the wound, coverage is obtained with the use of vascularized tissue using both muscle and fasciocutaneous flaps. The use of nondissolving polymethylmethacrylate and absorbable antibiotic-impregnated beads has been shown to deliver high concentrations of antibiotics with low systemic levels of the same antibiotic. We present a multicenter retrospective review of all cases that used absorbable antibiotic-impregnated beads for complex wound management from 2003 to 2013. A total of 104 cases were investigated, flap coverage was used in 97 cases (93.3%). Overall, 15 patients (14.4%) required reoperation with the highest groups involving orthopedic wounds and sternal wounds. The advantages of using absorbable antibiotic-impregnated beads in complex infected wounds have been demonstrated with minimal disadvantages. The utilization of these beads is expanding to a variety of complex infectious wounds requiring high concentrations of local antibiotics.