FMR1 Protein Expression Correlates with Intelligence Quotient in Both Peripheral Blood Mononuclear Cells and Fibroblasts from Individuals with an FMR1 Mutation.

Fragile X syndrome (FXS) is the most common heritable form of intellectual disability and is caused by CGG repeat expansions exceeding 200 (full mutation). Such expansions lead to hypermethylation and transcriptional silencing of the fragile X messenger ribonucleoprotein 1 (FMR1) gene. As a consequence, little or no FMR1 protein (FMRP) is produced; absence of the protein, which normally is responsible for neuronal development and maintenance, causes the syndrome. Previous studies have demonstrated the causal relationship between FMRP levels and cognitive abilities in peripheral blood mononuclear cells (PBMCs) and dermal fibroblast cell lines of patients with FXS. However, it is arguable whether PBMCs or fibroblasts would be the preferred surrogate for measuring molecular markers, particularly FMRP, to represent the cognitive impairment, a core symptom of FXS. To address this concern, CGG repeats, methylation status, FMR1 mRNA, and FMRP levels were measured in both PBMCs and fibroblasts derived from 66 individuals. The findings indicated a strong association between FMR1 mRNA expression levels and CGG repeat numbers in PBMCs of premutation males after correcting for methylation status. Moreover, FMRP expression levels from both PBMCs and fibroblasts of male participants with a hypermethylated full mutation and with mosaicism demonstrated significant association between the intelligence quotient levels and FMRP levels, suggesting that PBMCs may be preferable for FXS clinical studies, because of their greater accessibility.

CMV Infection Post Allogeneic Hematopoietic Stem Cell Transplantation in a Resource Limited Country.

Cytomegalovirus (CMV) infection is one of the common complications which can lead to significant morbidity and mortality in patients after allogeneic hematopoietic stem cell transplantation (HSCT). As the seroprevalence of CMV infection in Malaysia is high, this study aims to determine the prevalence of CMV infection in patients post HSCT and to evaluate the associated risk factors. Patients who underwent allogeneic HSCT in adult ward from 2008 to 2020 at a tertiary teaching hospital in Kuala Lumpur, Malaysia were studied retrospectively. They were followed up for a minimum of 100 days post-HSCT to determine the incidence of CMV infection. CMV infection was defined according to CMV Drug Development Forum 2014. Risk factors such as type of transplant, serostatus of donor and patients, age, gender, race, presence of graft versus host disease (GVHD) and underlying disease were included for analysis. A total of 112 patients were included. Forty (35.7%) patients had CMV infection with median of onset recorded as 40 days (range 13-95 days). Only haplo-identical HSCT and presence of GVHD were identified as significant risk factors. Patients who had CMV infection had a lower median survival time although this was not statistically significant. The CMV infection rate was comparable with previous reports in Asia and as expected, higher than the western countries. Therefore, vigilant monitoring of CMV infection should be implemented especially in patients who had haplo-identical HSCT and acute GVHD.

Evolution of Care and Outcomes Across Surges in Hospitalized Patients with Coronavirus Disease 2019.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has unfolded in distinct surges. Understanding how surges differ may reveal important insights into the evolution of the pandemic and improve patient care. METHODS: We leveraged the Michigan Medicine COVID-19 Cohort, a prospective observational study at an academic tertiary medical center that systematically enrolled 2309 consecutive patients hospitalized for COVID-19, comprising 5 distinct surges. RESULTS: As the pandemic evolved, patients hospitalized for COVID-19 tended to have a lower burden of comorbidities and a lower inflammatory burden as measured by admission levels of C-reactive protein, ferritin, lactate dehydrogenase, and D-dimer. Use of hydroxychloroquine and azithromycin decreased substantially after Surge 1, while use of corticosteroids and remdesivir markedly increased (P < .001 for all). In-hospital mortality significantly decreased from 18.3% in Surge 1 to 5.3% in Surge 5 (P < .001). The need for mechanical ventilation significantly decreased from 42.5% in Surge 1 to 7.0% in Surge 5 (P < .001), while the need for renal replacement therapy decreased from 14.4% in Surge 1 to 2.3% in Surge 5 (P < .001). Differences in patient characteristics, treatments, and inflammatory markers accounted only partially for the differences in outcomes between surges. CONCLUSIONS: The COVID-19 pandemic has evolved significantly with respect to hospitalized patient populations and therapeutic approaches, and clinical outcomes have substantially improved. Hospitalization after the first surge was independently associated with improved outcomes, even after controlling for relevant clinical covariates.

Histopathological evaluation of the effect of Salvadoria persica and Nigella sativa on the healing of tooth extraction socket in animal

To assess the effects of Salvadoria persica and Nigella sativa combination in tooth socket healing after extraction that can be a novel remedy for tooth extraction socket. Methods: Forty rabbits were included in this study, divided into two groups (control and experimental) with 20 rabbits. Upper right central incisors were extracted for all animals, the tooth sockets of the experimental group were dressed using an admix of Salvadoria persica and Nigella sativa immediately after irrigation with normal saline. In contrast, the extraction sockets of the control group were left without dressing. Biopsies were taken after euthanizing the animals at 1, 3, 7, and 14 days after treatment, histological examination was done for the samples at the given periods respectively. Results: On day 1 post-treatment, histological examination of the experimental group sections showed less acute inflammatory reaction than the control group. This continued to be reduced until the seventh day. The amount of granulation tissue formation was more in the experimental group along the different periods of the study, while new bone formation was observed after 1 week as woven bone, increased after 2 weeks and appeared as woven and lamellar bone in both experimental and control groups. Conclusions: A mixture of Salvadoria persica and Nigella sativa has an anti-inflammatory effect and accelerate bone healing by stimulating bone formation in the tooth extraction socket

PAK4 and NAMPT as Novel Therapeutic Targets in Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, and Mantle Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL), grade 3b follicular lymphoma (FL), and mantle cell lymphoma (MCL) are aggressive non-Hodgkin's lymphomas (NHL). Cure rates are suboptimal and novel treatment strategies are needed to improve outcomes. Here, we show that p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyl transferase (NAMPT) is critical for lymphoma subsistence. Dual targeting of PAK4-NAMPT by the Phase I small molecule KPT-9274 suppressed cell proliferation in DLBCL, FL, and MCL. Growth inhibition was concurrent with apoptosis induction alongside activation of pro-apoptotic proteins and reduced pro-survival markers. We observed NAD suppression, ATP reduction, and consequent cellular metabolic collapse in lymphoma cells due to KPT-9274 treatment. KPT-9274 in combination with standard-of-care chemotherapeutics led to superior inhibition of cell proliferation. In vivo, KPT-9274 could markedly suppress the growth of WSU-DLCL2 (DLBCL), Z-138, and JeKo-1 (MCL) sub-cutaneous xenografts, and a remarkable increase in host life span was shown, with a 50% cure of a systemic WSU-FSCCL (FL) model. Residual tumor analysis confirmed a reduction in total and phosphorylated PAK4 and activation of the pro-apoptotic cascade. This study, using various preclinical experimental models, demonstrates the therapeutic potential of targeting PAK4-NAMPT in DLBCL, FL, and MCL. The orally bioavailable, safe, and efficacious PAK4-NAMPT dual inhibitor KPT-9274 warrants further clinical investigation.

Data analytics competency and religiosity influence on external auditors' performance in Malaysia.

Background - Data analytics can support the external auditors' judgements. However, little is known about the external auditors' data analytics competency. Likewise, role of religiosity in enhancing the external auditors' performance is also inadequately investigated. This study examined: 1) the effects of data analytics competency on the external auditors' performance, and 2) the moderating effects of religiosity on data analytics competency and external auditors' performance relationship. Methods - Survey was conducted on 201 external auditors. Data analytics competency dimensions, namely, personal capabilities, professional expertise, technical skills, technologies and tools expertise were examined. Religiosity was measured by level and dimension (faith, virtue and optional). Results - Data analytics competency (personal capabilities) has a positive significant effect on the Muslim external auditors' performance. However, data analytics competency does not affect the performance of non-Muslim external auditors. Level of religiosity has significant moderating effect on the relationship between data analytics competency (technologies and tools expertise) and Muslim external auditors' performance. Nonetheless, level of religiosity does not moderate the relationship between data analytics competency and the performance of non-Muslim external auditors. Religiosity (virtue) has significant moderating effect on the relationship between data analytics competency (personal capabilities) and Muslim external auditors' performance. Meanwhile, religiosity (faith) has significant moderating effect on the relationship between data analytics competency (technologies and tools expertise) and non-Muslim external auditors' performance. Conclusion - This study demonstrates that data analytics competency and religiosity can influence the external auditors' performance.

Estimation of time utilized in suturing of oral flaps post-surgical wisdom teeth removal using Negus knot pusher instrument (a comparative study) / Estimativa do tempo utilizado na sutura de retalhos orais após exodontia de terceiros molares utilizando o instrumental Empurrador de nó Negus: um estudo comparativo

Objective: Wisdom teeth were the most common teeth affected among the rest of the teeth, these teeth need accurate evaluation and diagnosis, surgical removal of impacted wisdom needs time for incision, bone removal and suture, so the use of any instrument helps to reduce this time is essential. The objectives of this study were to estimate the time needed for the suture of oral flaps post-surgical removal of the lower wisdom teeth by using Negus knot pusher and compare it with the time used for stitching in conventional manual holding single stitching. Material and Methods: Data had been collected from thirty patients through history, clinical examination and radiographic assessment, followed by classical surgical removal performed on the same principles for all patients, at the suture level patients divided arbitrarily into two groups, control group 15 patients and 15 patients Negus pusher group, using Negus knot pusher, which is usually used to hold the stitch and stop bleeding post tonsillectomy operations by ligation, time elapsed for suturing with knot tying is calculated for both groups. Results: Among the 30 patients incorporated in the clinical study, control group mean was (1 minutes and 11 seconds and 70 milliseconds) while for the pusher group was (1 minutes and 32 seconds and 57 milliseconds), the comparison by means of T-test was not significant with the (0.424) value. Conclusion: the Negus pusher instrument can be used for the knotting stiches post wisdom teeth removal as an auxiliary tool and the time can be shortened by the use of a modified handling technique and more satisfaction for patients. (AU)

Objetivo: Os terceiros molares são os dentes mais afetados entre o resto dos dentes e necessitam de avaliação e diagnóstico precisos. A exodontia desses elementos impactados requer tempo para incisão, remoção óssea e sutura, portanto, é essencial o uso de instrumentos que ajudem a reduzir o tempo de procedimento. Os objetivos do presente estudo foram estimar o tempo necessário para a sutura de retalhos orais após a exodontia de terceiros molares inferiores utilizando o instrumental Empurrador de nó Negus (Negus Knot pusher) e compará-lo com o tempo necessário para a realização de sutura única convencional. Material e Métodos: Os dados foram coletados de 30 pacientes através da história, exame clínico e avaliação radiográfica, seguidos pela remoção cirúrgica clássica realizada através do mesmo princípio para todos os pacientes. Considerando o nível da sutura, os pacientes foram divididos arbitrariamente em dois grupos, grupo controle (n=15) e grupo Empurrador de nó Negus (n=15), o qual é geralmente utilizado para segurar o ponto e estancar o sangramento após cirurgia de tonsilectomia por ligadura. O tempo decorrido para sutura foi calculado para ambos os grupos. Resultados: Entre os 30 pacientes incluídos no estudo, a média do grupo controle foi de 1 minuto e 11 segundos e 70 milissegundos, enquanto para o grupo Empurrador de nó Negus foi de 1 minuto e 32 segundos e 57 milissegundos. A comparação intergrupo por meio do teste T não foi estatisticamente significativa (p=0,424). Conclusão: O instrumental Empurrador de nó Negus pode ser usado para sutura após a extração de terceiros molares como ferramenta auxiliar e o tempo pode ser reduzido pelo uso de uma técnica de manuseio modificada. Ademais, pode estar associado a maior satisfação dos pacientes. (AU)

Orofacial space infections, etiology, microbiological susceptibility and surgical management / Infecciones del espacio orofacial, etiología, susceptibilidad microbiológica y manejo quirúrgico

Orofacial infections are considered as one of most common infections and need rapid and adequate treatment as they affect a very delicate region and are associated with serious life-threatening complications. Orofacial infections can be either odontogenic that is with an origin in teeth and associated structures or non-odontogenic, not associated with teeth, can affect facial spaces and spread from one space to another, so a good knowledge about diagnosis and treating these infections is of utmost importance, and can include both non-surgical and surgical treatment. The aim of our study was to determine the most common cause of orofacial infections, the most common bacterial microorganisms and their antibiotic susceptibility. Materials and Methods: A descriptive study was undertaken in the Department of Oral and Maxillofacial Surgery, Al-Shaheed Ghazi Al-Hariry Hospital, Baghdad, Iraq from 1st January to 30th September 2015. This study included 45 patients with different forms of orofacial infections; data regarding age, gender, underlying cause, facial space involvement, presenting signs were collected through history, clinical examination and radiographs, incision and drainage with swab sample for culture and sensitivity test was performed. Results: Patients with orofacial infections showed a female to male ratio of 1.25:1. The mean age was 32.8 years. Most of the patients were in their 4th decade of life (27%). Most infections were odontogenic in origin (62%), the most common facial space involved was submandibular (65%), the most common isolated microorganism was Streptococcus pyogenes (59%), and most patients were treated using an extra-oral surgical approach (78%). Antibiotics to which bacterial isolated showed the most sensitivity were netilmicin, cefoperazone and rifampicin (91%). Pain and limitation of mouth opening gradually decreased in most of patients during the two weeks follow up period. Conclusion: Orofacial infections were more common in females, in the third and fourth decade of life, were odontogenic in origin, were mostly caused by Streptococcus pyogenes, and most isolates were susceptible to netilmicin, cefoperazone and rifampicin. Pain and trismus decreased over two weeks post-treatment.

Las infecciones orofaciales se consideran una de las infecciones más comunes y necesitan un tratamiento rápido y adecuado, ya que afectan una región muy delicada y se asocian con complicaciones graves que amenazan la vida. Las infecciones orofaciales pueden ser odontogénicas que se originan en los dientes y las estructuras asociadas, o no odontogénicas, no asociadas con los dientes, pueden afectar los espacios faciales y propagarse de un espacio a otro, por lo que un buen conocimiento sobre el diagnóstico y el tratamiento de estas infecciones es de suma importancia, y puede incluir tratamiento no quirúrgico y quirúrgico. El objetivo de nuestro estudio fue determinar la causa más común de infecciones orofaciales, los microorganismos bacterianos más comunes y su susceptibilidad a los antibióticos. Material y Métodos: se realizó un estudio descriptivo en el Departamento de Cirugía Oral y Maxilofacial, Hospital Al-Shaheed Ghazi Al-Hariry, Bagdad, Iraq del 1 de enero al 30 de septiembre de 2015. Este estudio incluyó a 45 pacientes con diferentes formas de infecciones orofaciales; Se recopilaron datos sobre edad, sexo, causa subyacente, afectación del espacio facial, signos de presentación a través de la historia, examen clínico y radiografías, incisión y drenaje con muestra de hisopo para cultivo y prueba de sensibilidad. Resultado: Los pacientes con infecciones orofaciales mostraron una relación mujer/hombre de 1.25: 1. La edad media fue de 32,8 años. La mayoría de los pacientes estaban en su cuarta década de vida (27%). La mayoría de las infecciones fueron de origen odontogénico (62%), el espacio facial más común involucrado fue submandibular (65%), el microorganismo aislado más común fue Streptococcus pyogenes (59%), y la mayoría de los pacientes fueron tratados con un abordaje quirúrgico extraoral (78%). Los antibióticos a los que las bacterias aisladas mostraron mayor sensibilidad fueron netilmicina, cefoperazona y rifampicina (91%). El dolor y la limitación de la apertura de la boca disminuyeron gradualmente en la mayoría de los pacientes durante el período de seguimiento de dos semanas. Conclusión:Las infecciones orofaciales fueron más comunes en las mujeres, en la tercera y cuarta década de la vida, fueron de origen odontogénico, fueron causadas principalmente por Streptococcus pyogenes y la mayoría de los aislamientos fueron susceptibles a la netilmicina, cefoperazona y rifampicina. El dolor y el trismo disminuyeron durante las dos semanas posteriores al tratamiento.

Impact of the TiO2 Nanosolution Concentration on Heat Transfer Enhancement of the Twin Impingement Jet of a Heated Aluminum Plate.

Here, the researchers carried out an experimental analysis of the effect of the TiO2 nanosolution concentration on the heat transfer of the twin jet impingement on an aluminum plate surface. We used three different heat transfer enhancement processes. We considered the TiO2 nanosolution coat, aluminum plate heat sink, and a twin jet impingement system. We also analyzed several other parameters like the nozzle spacing, nanosolution concentration, and the nozzle-to-plate distance and noted if these parameters could increase the heat transfer rate of the twin jet impingement system on a hot aluminum surface. The researchers prepared different nanosolutions, which consisted of varying concentrations, and coated them on the metal surface. Thereafter, we carried out an X-ray diffraction (XRD) and a Field Emission Scanning Electron Microscopy (FESEM) analysis for determining the structure and the homogeneous surface coating of the nanosolutions. This article also studied the different positions of the twin jets for determining the maximal Nusselt number (Nu). The researchers analyzed all the results and noted that the flow structure of the twin impingement jets at the interference zone was the major issue affecting the increase in the heat transfer rate. The combined influence of the spacing and nanoparticle concentration affected the flow structure, and therefore the heat transfer properties, wherein the Reynolds number (1% by volume concentration) maximally affected the Nusselt number. This improved the performance of various industrial and engineering applications. Hypothesis: Nusselt number was affected by the ratio of the nanoparticle size to the surface roughness. Heat transfer characteristics could be improved if the researchers selected an appropriate impingement system and selected the optimal levels of other factors. The surface coating with the TiO2 nanosolution also positively affected the heat transfer rate.