Impact of Obesity on Outcomes Associated With Acute Alcoholic Pancreatitis.

The incidence and prevalence of obesity have been rising in the United States, negatively impacting the population's overall health. This study seeks to better understand the impact of obesity on patients presenting with acute alcoholic pancreatitis (AAP). Data collected using the National Inpatient Sample (NIS) from the fourth quarter of 2015 to 2019 with a principal diagnosis of AAP and secondary obesity were analyzed. Confounders were adjusted for multivariate regression analysis using a multitude of factors. A total of 229,510 patients were identified with a diagnosis of AAP, among which 14,150 were also identified as obese. A majority of the sample, both obese and non-obese patients with AAP, were middle-aged white females. The average comorbidity index (CCI) was lower in the non-obese cohort compared to the obese cohort. Compared to non-obese patients, patients with AAP who were obese had higher hospital charges and a longer LOS (p<0.05. Additionally, compared to non-obese patients, obese patients with AAP had higher odds of mortality and adverse events, such as acute renal failure and respiratory failure (p<0.05). Current research supports these complications, which have shown an association with increased visceral fat in or around the pancreas that can ultimately worsen acute pancreatitis outcomes and aggravate AAP by damaging the intestinal mucosal barrier. These findings should be considered when treating obese patients who develop AAP. Strategies to increase surveillance of such patients should be implemented to reduce complications and mortality in this population.

Pregnancy-Related Eccrine Angiomatous Hamartoma: Case Report.

Eccrine angiomatous hamartoma is rare, slow-growing, and benign neoplasm that is diagnosed based on clinical characteristics and histological findings. It usually presents as a solitary nodule on the extremities and may arise at birth or in childhood. Although it is usually asymptomatic, in some cases it can cause pain and hyperhidrosis. From a histological perspective, it is characterized by an increase in the number of eccrine glands and a proliferation of vascular channels. We present the case of a 26-year-old woman who developed an eccrine angiomatous hamartoma in her right leg. The rapid growth of the lesion during pregnancy coupled with the challenges posed by a superficial biopsy, complicated the differential diagnosis.

Fluid-structure interaction analysis of amniotic fluid with fetus and placenta inside uterus exposed to military blasts.

INTRODUCTION: Pregnancy-related trauma is one of the leading causes of morbidity and mortality in pregnant women and fetuses. The fetal response to injury is largely dependent on the timing of fetal presentation and the underlying pathophysiology of the trauma. The optimal management of pregnant patients who have suffered an obstetric emergency depends on clinical assessment and understanding of the placental implantation process, which can be difficult to perform during an emergency. Understanding the mechanisms of traumatic injuries to the fetus is crucial for developing next-generation protective devices. METHODS: This study aimed to investigate the effect of amniotic fluid on mine blast on the uterus, fetus, and placenta via computational analysis. Finite element models were developed to analyze the effects of explosion forces on the uterus, fetus, and placenta, based on cadaveric data obtained from the literature. This study uses computational fluid-structure interaction simulations to study the effect of external loading on the fetus submerged in amniotic fluid inside of the uterus. RESULTS: Computational fluid-structure interaction simulations are used to study the effect of external loading on the fetus/placenta submerged in amniotic fluid inside the uterus. Cushioning function of the amniotic fluid on the fetus and placenta is demonstrated. The mechanism of traumatic injuries to the fetus/placenta is shown. DISCUSSION: The intention of this research is to understand the cushioning function of the amniotic fluid on the fetus. Further, it is important to make use of this knowledge in order to ensure the safety of pregnant women and their fetuses.

Optimizing needle length and site choice for adult immunization.

BACKGROUND: Current recommendations for needle length and vaccination site for intramuscular deltoid vaccinations are backed by minimal data. AIM: To determine the ideal needle length and vaccination site for intramuscular deltoid vaccine administration. METHODS: 120 shoulder CT scans were evaluated and grouped by patient weight and sex as recommended by the United States CDC: Group 1, <60 kg, Group 2, 60-70 kg, Group 3, females 70-90 kg and males 70-118 kg, and Group 4, females > 90 kg and males > 118 kg. For each group, distance from skin to deltoid fascia and deltoid muscle width were measured at 2, 4, and 6 cm distal to the posterolateral corner of the acromion for 5 unique trajectories. Needle lengths of 0.625″, 1.0″, and 1.5″ were simulated at each site to determine inoculation location relative to the deltoid. RESULTS: For Group 1, a 0.625″ needle in the mid-lateral (ML) trajectory 4 cm distal to the posterolateral corner provided a perfect rate of successful inoculations (100 %). For Groups 2-3, a 1″ needle in the posterolateral (PL) trajectory 4 cm distal provided high rates (>80 %) of successful intramuscular inoculations with low rates of overpenetration (<15 %) while minimizing risk to the axillary nerve. For Group 4, a 1.5″ needle using the same strategy provided the highest rate of successful inoculations (96 %) and minimal overpenetration (4 %). Overpenetration was associated with more anterior and superior injection sites (P < 0.001 for both) for all needle lengths. CONCLUSIONS: The overall ideal injection site to maximize successful intramuscular vaccine administration, minimize overpenetration, and avoid axillary nerve injury is 4 cm distal to and in line with the posterolateral corner of the acromion, a site more posterior and inferior than current CDC recommendations. We caution against use of a 1.5″ needle for patients < 118 kg due to high predicted rates of overpenetration.

Outcomes After Minimally Invasive Sacroiliac Joint Fusion: A Scoping Review.

BACKGROUND: Sacroiliac joint (SIJ) dysfunction is a significant contributor to lower back pain. Although open surgical treatment for persistent pain has long been the standard, it is associated with significant surgical morbidity, high complication rates, and variable patient satisfaction. Minimally invasive SIJ fusion (MISJF) is a promising and effective approach. This scoping review was carried out to map the available evidence on outcomes after MISJF. METHODS: This review was conducted in accordance with the PRISMA guidelines. Inclusion criteria were all full-text articles reporting on functional, clinical, and quality-of-life outcomes after MISJF. Exclusion criteria consisted of studies including patients with traumatic sacroiliac injuries or congenital spinal abnormalities, and procedures involving multiple spinal fusions or an open approach to SIJ fusion. RESULTS: A total of 1305 studies were identified across 6 databases. After duplicate removal and further screening, 33 independent studies were included in our review. Regarding pain management, 21 studies reported visual analog scale scores, and all showed significant (>50%) reductions in pain at multiple time points postoperatively. Six studies reported on quality-of-life outcomes and showed significant increases, especially compared with nonsurgical treatment. CONCLUSIONS: This study highlights the existing literature regarding outcomes after MISJF. MISJF provides favorable responses in quality-of-life metrics, pain scores, and overall postoperative outcomes in select patients. Although outcomes have been widely studied, more studies, especially prospectively designed and those without industry influence, should be performed to elucidate the optimal management of patients with intractable SIJ pain.

A Rare Case of Diffuse Nodular Lymphoid Hyperplasia With Rectal Involvement.

Nodular lymphoid hyperplasia (NLH) is characterized by the growth of multiple discrete small submucosal nodules specifically confined to the lamina propria and superficial submucosa layers of the intestinal wall. Gastric and rectal involvement of NLH is exceedingly rare. To date, few case reports have described diffuse NLH presenting with multiple submucosal lymphomatous polyposis occurring in the rectum.  Our patient is a 39-year-old morbidly obese Hispanic female who presented to the gastroenterology clinic complaining of intermittent hematochezia for the past six months. Colonoscopy showed diffuse nodularity in the sigmoid colon and rectal mucosa, extending 20 cm from the rectal verge. Rectal biopsies revealed moderate active chronic inflammation predominantly of lymphoplasmacytic cells with areas of lymphoid hyperplasia and focal surface ulceration. Immunohistochemistry stains revealed reactive lymphoid hyperplasia (RLH).  The NLH is a risk factor for extraintestinal and intestinal lymphomas. When encountering lymphoid hyperplasias, the possibility of malignancy must always be considered. It is crucial to monitor patients with NLH via capsule endoscopies, small bowel series, and colonoscopy for surveillance of new lesions in light of the potential for malignancy.

Innovation-Oriented Medical School Curricula: Review of the Literature.

Innovation and entrepreneurship (I&E) programs in medical education have become available as medical schools recognize the need to train forward-thinking physicians. There is considerable diversity in the design and implementation of these curricula, which represents a challenge and possibly serves as a deterrent for the development of additional I&E programs. A comprehensive search of medical school I&E programs and review of all Association of American Medical Colleges member websites (n = 171) were conducted. This review sought to (1) identify all American and Canadian allopathic medical schools with I&E curricula, (2) evaluate their structure/integration in the context of medical education, (3) outline core learning themes, and (4) describe the evaluative metrics. Information was collected through published or publicly available websites and through a questionnaire sent to identified I&E program leaders. Twenty-eight I&E-oriented medical education programs were identified from 26 schools; all of the programs integrated faculty leadership with backgrounds in medicine, engineering, and/or business/entrepreneurship. Of the programs, 57% (16/28) had been launched within the past four years and 75% (21/28) based program enrollment on a selective application process. Nearly all (27/28) incorporated lecture series and/or hands-on modules as a teaching technique. The most prevalent metric was completion of a capstone project (22/28; 79%). At least 15.2% (26/171) of American and Canadian allopathic medical schools include the option for students to participate in an I&E curriculum-based program. This review can be used to help medical school faculty with developing I&E curricula.

Fluid-Structure Interaction Analyses of Biological Systems Using Smoothed-Particle Hydrodynamics.

Due to the inherent complexity of biological applications that more often than not include fluids and structures interacting together, the development of computational fluid-structure interaction models is necessary to achieve a quantitative understanding of their structure and function in both health and disease. The functions of biological structures usually include their interactions with the surrounding fluids. Hence, we contend that the use of fluid-structure interaction models in computational studies of biological systems is practical, if not necessary. The ultimate goal is to develop computational models to predict human biological processes. These models are meant to guide us through the multitude of possible diseases affecting our organs and lead to more effective methods for disease diagnosis, risk stratification, and therapy. This review paper summarizes computational models that use smoothed-particle hydrodynamics to simulate the fluid-structure interactions in complex biological systems.

Hematopoietic stem cell- and induced pluripotent stem cell-derived CAR-NK cells as reliable cell-based therapy solutions.

Hematopoietic stem cell- (HSC) and induced pluripotent stem (iPS) cell-derived natural killer (NK) cells containing engineered functions, such as chimeric antigen receptors (CAR), offer great promise for the treatment of seemingly incurable oncological malignancies. Today, some of the main challenges of CAR cell-based therapeutics are the long manufacturing time and safety of the cell sources used. Additional challenges include avoiding graft vs host disease (GVHD) and cytokine release syndrome (CRS). Here, we show compelling evidence for the use of NK cell therapeutics as a reliable off-the-shelf option, as they address key issues. Furthermore, we highlight how iPS cells and directed differentiation toward HSC and NK cells address industrial scalability and safety.

Using High-Content Screening to Generate Single-Cell Gene-Corrected Patient-Derived iPS Clones Reveals Excess Alpha-Synuclein with Familial Parkinson's Disease Point Mutation A30P.

The generation of isogenic induced pluripotent stem cell (iPSC) lines using CRISPR-Cas9 technology is a technically challenging, time-consuming process with variable efficiency. Here we use fluorescence-activated cell sorting (FACS) to sort biallelic CRISPR-Cas9 edited single-cell iPSC clones into high-throughput 96-well microtiter plates. We used high-content screening (HCS) technology and generated an in-house developed algorithm to select the correctly edited isogenic clones for continued expansion and validation. In our model we have gene-corrected the iPSCs of a Parkinson's disease (PD) patient carrying the autosomal dominantly inherited heterozygous c.88G>C mutation in the SNCA gene, which leads to the pathogenic p.A30P form of the alpha-synuclein protein. Undertaking a PCR restriction-digest mediated clonal selection strategy prior to sequencing, we were able to post-sort validate each isogenic clone using a quadruple screening strategy prior to generating footprint-free isogenic iPSC lines, retaining a normal molecular karyotype, pluripotency and three germ-layer differentiation potential. Directed differentiation into midbrain dopaminergic neurons revealed that SNCA expression is reduced in the gene-corrected clones, which was validated by a reduction at the alpha-synuclein protein level. The generation of single-cell isogenic clones facilitates new insights in the role of alpha-synuclein in PD and furthermore is applicable across patient-derived disease models.

Combined Posterior-Anterior Interbody Fusion in the Management of Traumatic Lumbosacral Dissociation: A Case Report and Review of Literature.

Traumatic lumbosacral dissociation is a unique, but well-documented, phenomenon that generally stems from high-energy impact injuries to the lower lumbar spine. Patients typically present with complicated and multisystem injuries with wide-ranging neurological deficits below the level of trauma. This presents stark challenges regarding the diagnosis, management, and surgical correction technique utilized. In this study, we present the case of a 21-year-old, morbidly obese, male patient that presented after a traumatic motor vehicle accident with L5-S1 lumbosacroiliac dissociation, cauda equina syndrome, and left lower extremity monoplegia. The degree of disruption warranted a 360° approach, we opted for an anterior lumbar interbody fusion followed by a posterior, lumbar interbody, short segment fusion. We review the case and relevant literature of similar lumbosacral dissociation studies with their management options and outcomes. Due to the rare nature of these devastating injuries, there remains wide variability in their management, with a combination of open anterior and posterior approaches resulting in variable long-term outcomes. The management of these rare injuries will require appropriate consideration of the patient's unique etiology, coexisting injuries, and radiological imaging in deciding surgical stabilization techniques.

Case of Pott's Disease in a 17-Year-Old Patient in the Dominican Republic.

Pott's disease, or spinal tuberculosis, is caused by the pathogen Mycobacterium tuberculosis. Although tuberculosis is endemic in developing countries, such as Dominican Republic, Pott's disease is rarely seen, only representing 1% of the total cases. Due to its low incidence, this could be easily misdiagnosed. We report a case of a 17-year-old male with a history of pleural effusion that presented with severe back pain. Several imaging studies reported an aggressive paravertebral neoplasia at the thoracic levels. A surgical biopsy was performed, and the procedure revealed bone fragmentation, which prompted the need to rule out Pott's disease per current recommendations. Biopsy and subsequent positive QuantiFERON-TB Gold test confirmed spinal tuberculosis.

La microalbuminuria como factor pronóstico en un grupo de pacientes hipertensos de una entidad de primer nivel de atención de Manizales (Colombia), 2010 / The microalbuminuria as factor prognosis in a group of hypertense patients of an entity of 1º level of attention of Manizales (Colombia), 2010

Objetivos: Determinar el valor de la microalbuminuria en un grupo de pacientes hipertensos. Materiales y métodos: Se estudiaron pacientes inscritos en el programa de vigilancia y control de la hipertensión arterial de ASSBASALUD ESE (Manizales, Colombia), clasificados como de riesgo bajo y moderado. Se diseñó un estudio transversal para el análisis de los factores de riesgo asociados: dislipidemia, obesidad, diabetes mellitus, infarto agudo de miocardio relacionándolos con los niveles de microalbuminuria encontrados en la investigación. Resultados: El estudio se hizo con 86 pacientes hipertensos (76,7% mujeres). En 16,7% (Ic95%: 9,4-26,45) de ellos los niveles de microalbuninuria se encontraron alterados. Las cifras halladas estuvieron entre 95,1mg/dl, valor máximo, y una cifra mínima de 0,1mg/ dl. El valor promedio fue de 11,77mg/dl. En 34,9% de los pacientes se registraron antecedentes patológicos, en 74,2% el antecedente fue dislipidemia y obesidad en el 32% de los casos. 64% de los pacientes tenían antecedentes familiares patológicos, hipertensión arterial en el 30,9% e infarto del miocardio en el 16,4%. Se encontró relación significativa entre microalbuminuria y el valor de índice de masa corporal (p=0,028). Conclusiones: La frecuencia de microalbuminuria positiva relacionada con dislipidemia fue similar a la obtenida en otros estudios. Se encontró una elevada prevalencia de microalbuminuria alterada en pacientes con dislipidemia. La frecuencia de microalbuminuria anormal encontrada en la población estudiada indica presencia de riesgo cardiovascular.

Objective: To determine the value of microalbuminuria in a group of hypertensive patients. Materials and methods: Patients subscribed to the arterial-hypertension monitor and control program of ASSBASALUD E.S.E. (Manizales, Caldas) where studied. The patients were classified as low and moderate risk. And a cross-sectional study was designed for the analysis of the associated risk factors: dyslipidemia, obesity, diabetes Mellitus, acute myocardial infarction relating these factors with the microalbuminuria values found during the investigation. Results: The study was made with 86 hypertensive patients (76.7% women). In 16,7% the levels of microalbuminuria where abnormal. The found values had as maximum 95,1 mg/dl, and minimum 0,1 mg/dl with an average of 13,58 mg/dl. 34.9% of the patients registered pathological antecedents, in 74.2% the antecedent was dislipidemia and in 32% obesity. 64% of the patients had pathological family antecedents, 30% arterial hypertension and 16.4% myocardial infarction. A significant relation was found between the MA and the body mass index (p=0.028). Conclusions: The frequency of microalbuminuria related to dyslipidemia was similar to that obtained in other studies. A high prevalence was found of altered microalbuminuria in patients with dyslipidemia. The frequency of abnormal microalbuminuria found in the studied population indicates the presence of cardiovascular risk factor.

Prevalencia de protozoos intestinales en 79 niños de 2 a 5 años de edad de un hogar infantil estatal en Circasia, Quindío / Prevalence of intestinal protozoa in 79 children 2 to 5 years old from a state nursery program in Circasia, Quindío

Introducción: Los parásitos intestinales se consideran un problema de salud pública en los países en desarrollo y afecta a individuos de todas las edades y sexos, pero se presentan, sobre todo, en los primeros años de vida. En la actualidad, entre las parasitosis más reportadas para el departamento del Quindío se encuentra la giardiasis, producida por Giardia intestinalis (G. duodenalis o G. lamblia), y la blastocistocis, producida por Blastocystis sp. Objetivo: Determinar la prevalencia de protozoos intestinales en 79 niños con edades comprendidas entre los 2 y 5 años, de un hogar infantil en el municipio de Circasia, Quindío.Materiales y métodos: Se recolectaron tres muestras de heces en 79 niños con previo consentimiento del tutor legal. Las muestras fueron sometidas al análisis de laboratorio por examen directo macroscópico y microscópico, utilizando lugol al 1%, solución salina al 0,83%, solución salina-eosina y la técnica de concentración de Ritchie o formol-éter. Resultados: Para los tres muestras, los parásitos con potencial patógeno tuvieron las siguientes prevalencias: Blastocystis sp., 49,4%, 57% y 64,6%; G. lamblia, 16,5%, 22,8% y 15,2 %; complejo Entamoeba histolytica/dispar, 5,1%, 5,1% y 1,3%, respectivamente. Conclusiones: Este estudio muestra la elevada prevalencia de parásitos protozoarios, y Blastocystis sp. fue el más prevalente. Durante el seguimiento se detectó reinfestación de los niños que participaron en el estudio.

Introduction: Intestinal parasites are considered a public health problem in developing countries, and they affect individuals of all ages and sexes; nevertheless they are frequent in early childhood. At present, the most reported intestinal parasite conditions in Quindío are giardiasis, caused by Giardia intestinalis (G. lamblia or G.duodenalis), and blastocystosis caused by Blastocystis sp. Objective: The objective is to determine the prevalence of intestinal parasites in children 2 to 5 years old at a State nursery in Circasia, Quindio. Materials and methods: Three fecal samples per child were collected from 79 children following informed consent from their legal guardians. Microscopic and macroscopic laboratory test were made using 1 % Lugol, 0,8 % saline solution, saline-eosin solution and concentration techniques with formaldehyde-ether (Ritchie.) Results: In the three fecal samples, the pathogen parasites had the following prevalence: Blastocystis sp 49,4 %, 57 % and 64,6 % sp; Giardia lamblia 16,5 %, 22,8 % and 15,2 %; and Entamoeba histolytica/dispar 5,1 %, 5,1 % and.1,3 % respectively.Conclusions: This study shows a high frequency of protozoa parasites, Blastocystis sp being the most prevalent. Re-infection in children was detected during the study.

NPR1 preferentially binds to the DNA-inactive form of Arabidopsis TGA2.

Systemic acquired resistance (SAR) is triggered by hormone defense cues and is associated with the onset of expression of pathogenesis-related (PR) genes that encode for anti-microbial proteins in plants. In the case of PR-1, transcriptional activation involves promoter-specific recruitment of transcription factors such as TGA2 through a mechanism that may involve transient physical interaction with the NPR1 protein. This stimulus-inducible recruitment process has yet to be fully explained at the functional and mechanistic level. To investigate this question further, we initially looked to see whether NPR1 preferentially forms a complex with the DNA bound or unbound fraction of TGA2. As shown here, NPR1 appears to preferentially interact with the non-DNA bound fraction of TGA2. We subsequently mutated this transcription factor to identify key residues in its conserved carboxyl terminal (CT) domain that mediate complex formation with NPR1. These approaches revealed that two non-overlapping regions of the CT domain of TGA2 bind independently to NPR1. The specificity and biological significance of these findings were inferred with a mutant form of NPR1 that fails to activate SAR in vivo. These and other findings raise the possibility that NPR1 may transiently interact with the DNA unbound fraction of TGA2 to promote its recruitment to an active form on cognate target promoters.

Development of Arabidopsis whole-genome microarrays and their application to the discovery of binding sites for the TGA2 transcription factor in salicylic acid-treated plants.

We have developed two long-oligonucleotide microarrays for the analysis of genome features in Arabidopsis thaliana, in particular for the high-throughput identification of transcription factor-binding sites. The first platform contains 190,000 probes representing the 2-kb regions upstream of all annotated genes at a density of seven probes per promoter. The second platform is divided into three chips, each of over 390,000 features, and represents the entire Arabidopsis genome at a density of one probe per 90 bases. Protein-DNA complexes resulting from the formaldehyde fixation of leaves of plants 2 h after exposure to 1 mm salicylic acid (SA) were immunoprecipitated using antibodies against the TGA2 transcription factor. After reversal of the cross-links and amplification, the resulting ChIP sample was hybridized to both platforms. High signal ratios of the ChIP sample versus raw chromatin for clusters of neighboring probes provided evidence for 51 putative binding sites for TGA2, including the only previously confirmed site in the promoter of PR-1 (At2g14610). Enrichment of several regions was confirmed by quantitative real-time PCR. Motif search revealed that the palindromic octamer TGACGTCA was found in 55% of the enriched regions. Interestingly, 15 of the putative binding sites for TGA2 lie outside the presumptive promoter regions. The effect of the 2-h SA treatment on gene expression was measured using Affymetrix ATH1 arrays, and SA-induced genes were found to be significantly over-represented among genes neighboring putative TGA2-binding sites.

Salicylic acid and NPR1 induce the recruitment of trans-activating TGA factors to a defense gene promoter in Arabidopsis.

Efforts to elucidate the contributions by transcription factors to plant gene expression will require increasing knowledge of their specific in vivo regulatory associations. We are systematically investigating the role of individual TGA factors in the transcriptional control of pathogenesis-related (PR) defense genes, whose expression is stimulated in leaves by salicylic acid (SA) through a stimulus pathway involving NPR1. We focused on PR-1 because its SA-induced expression in Arabidopsis is mediated by an as-1-type promoter cis element (LS7) that is recognized in vitro by TGA factors. We found that two NPR1-interacting TGA factors, TGA2 and TGA3, are the principal contributors to an LS7 binding activity of leaves that is enhanced by SA through NPR1. The relevance of these findings to PR-1 expression was investigated by the use of chromatin immunoprecipitation, which demonstrated that in vivo these TGA factors are strongly recruited in an SA- and NPR1-dependent manner to the LS7-containing PR-1 promoter. Significantly, the timing of promoter occupancy by these factors is linked to the SA-induced onset and sustained expression of PR-1. Because leaf transfection assays indicate that TGA3 activates transcription, as noted previously for TGA2, these two TGA factors are predicted to make positive contributions to the expression of this target gene. Thus, the findings presented here distinguish among different modes of regulation by these transcription factors and provide strong support for their direct role in the stimulus-activated expression of an endogenous defense gene.