Tumor versus Tumor Cell Targeting in Metal-Based Nanoparticles for Cancer Theranostics.

The application of metal-based nanoparticles (mNPs) in cancer therapy and diagnostics (theranostics) has been a hot research topic since the early days of nanotechnology, becoming even more relevant in recent years. However, the clinical translation of this technology has been notably poor, with one of the main reasons being a lack of understanding of the disease and conceptual errors in the design of mNPs. Strikingly, throughout the reported studies to date on in vivo experiments, the concepts of "tumor targeting" and "tumor cell targeting" are often intertwined, particularly in the context of active targeting. These misconceptions may lead to design flaws, resulting in failed theranostic strategies. In the context of mNPs, tumor targeting can be described as the process by which mNPs reach the tumor mass (as a tissue), while tumor cell targeting refers to the specific interaction of mNPs with tumor cells once they have reached the tumor tissue. In this review, we conduct a critical analysis of key challenges that must be addressed for the successful targeting of either tumor tissue or cancer cells within the tumor tissue. Additionally, we explore essential features necessary for the smart design of theranostic mNPs, where 'smart design' refers to the process involving advanced consideration of the physicochemical features of the mNPs, targeting motifs, and physiological barriers that must be overcome for successful tumor targeting and/or tumor cell targeting.

Smart Design of ZnFe and ZnFe@Fe Nanoparticles for MRI-Tracked Magnetic Hyperthermia Therapy: Challenging Classical Theories of Nanoparticles Growth and Nanomagnetism.

Iron Oxide Nanoparticles (IONPs) hold the potential to exert significant influence on fighting cancer through their theranostics capabilities as contrast agents (CAs) for magnetic resonance imaging (MRI) and as mediators for magnetic hyperthermia (MH). In addition, these capabilities can be improved by doping IONPs with other elements. In this work, the synthesis and characterization of single-core and alloy ZnFe novel magnetic nanoparticles (MNPs), with improved magnetic properties and more efficient magnetic-to-heat conversion, are reported. Remarkably, the results challenge classical nucleation and growth theories, which cannot fully predict the final size/shape of these nanoparticles and, consequently, their magnetic properties, implying the need for further studies to better understand the nanomagnetism phenomenon. On the other hand, leveraging the enhanced properties of these new NPs, successful tumor therapy by MH is achieved following their intravenous administration and tumor accumulation via the enhanced permeability and retention (EPR) effect. Notably, these results are obtained using a single low dose of MNPs and a single exposure to clinically suitable alternating magnetic fields (AMF). Therefore, as far as the authors are aware, for the first time, the successful application of intravenously administered MNPs for MRI-tracked MH tumor therapy in passively targeted tumor xenografts using clinically suitable conditions is demonstrated.

Rates of Readmission and Emergency Department Visits of Publicly Versus Commercially Insured Patients in a Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program Accredited Center.

Background: Patients with governmental insurance are known to utilize the emergency department (ER) at a higher rate and have higher readmission rates than other patients. Twenty percent of our patients are publicly insured. Our objective was to determine if there was a higher rate of readmissions and ER visits within 30 days in publicly insured patients. Methods: Data was analyzed from a single center submitted to the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program Participant Use Data File from January 1, 2015 to December 31, 2018. We added insurance status and described quantitative variables using mean, and standard deviation (SD). These were reported as regression coefficients (RC) and prevalence ratio (PR), along with their 95% confidence interval (CI). P values of less than 5% were considered statistically significant. Results: The overall rate of ER visits, readmissions, and reoperations were 3.5%, 7.4%, and 2.2% respectively. Medicaid and Medicare patients were found to have longer operative times, 62.7 minutes vs 57.5 minutes (p = 0.35). Patients on public insurance had higher adjusted risk of ER visits (PR 1.43, 95% CI: 0.41-5.3; p = 0.58) and readmissions (PR 1.64, 95% CI: 0.76-3.55; p = 0.21) than patients on commercial/self-pay insurance. Re-operations were lower in the publicly insured group (PR 0.93, 95% CI: 0.2-4.7; p = 0.92) than patients on commercial/self-pay insurance. However, these outcomes were not statistically significant. Conclusions: Publicly insured patients tend to have a higher adjusted risk of ER visits and readmissions but was not statistically significant. The rate of re-operation was slightly lower in publicly insured patients.

Does accreditation matter? An analysis of complications of bariatric cases using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program and National Quality Improvement Program databases.

BACKGROUND: Two large nationwide databases collect data on common operations in the United States. The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) collects bariatric data, whereas the National Quality Improvement Program (NSQIP) gathers details on a broader range of general surgical cases. OBJECTIVE: Evaluate the differences in rates of complications between both databases regarding Roux-en-Y gastric bypass and sleeve gastrectomy. SETTING: National databases, United States. METHODS: We evaluated the MBSAQIP and NSQIP from 2017 to 2019 using the procedure codes 43644 and 43775. Fifteen common complications were evaluated. Propensity-matched analyses (PMAs) were done to control for differences across databases. Significantly different variables after a PMA were included in multivariable models. The data were examined for differences between the 2 databases before and after the PMA, with and without adjustment for operation type. RESULTS: There were 483,361 cases reported in the MBSAQIP and 57,598 in the NSQIP. PMA matched 57,479 cases for each database. Seven complications were different, with higher rates reported in the NSQIP than in the MBSAQIP: myocardial infarction, sepsis, organ/space surgical site infections, deep vein thrombosis, urinary tract infections, pulmonary embolism, ventilator dependence >48 hours, and pneumonia. When adjusting for the procedure performed, sleeve gastrectomy in the NSQIP had higher rates of organ/space surgical site infections, deep vein thrombosis, sepsis, and death. Roux-en-Y gastric bypass in the NSQIP had higher rates of organ/space surgical site infections, ventilator dependence >48 hours, urinary tract infections, myocardial infarction, deep vein thrombosis, and sepsis. CONCLUSION: When compared with the MBSAQIP, the NSQIP reports higher rates of bariatric complications. Further studies are needed to confirm the reasons behind this.

Is fundoplication necessary after paraesophageal hernia repair? A meta-analysis and systematic review.

INTRODUCTION: Paraesophageal hernias are often asymptomatic, but when symptomatic they should be fixed laparoscopically. A cruroplasty of the diaphragmatic pillars is performed and a fundoplication is usually performed at the time. However, there are times, especially in emergency cases, where it is not always possible to perform a fundoplication. We hypothesized there would be no difference in outcomes whether or not a fundoplication is performed as part of a paraesophageal hernia repair. METHODS: A literature review of available clinical databases was performed using PubMed, Clinical Key and Google Scholar. Our search terms were: "paraesophageal hernia" "paraesophageal hernia repair" "fundoplication" "emergency surgery" "no fundoplication" We excluded studies that were in languages other than English, abstracts and small case series. RESULTS: Our search criteria yielded a total of 22 studies published between 1997 and 2020. There were a total of 8600 subjects enrolled into this study. The overall pooled prevalence of fundoplication were estimated as 69% (95% CI: 59%-78%). In patients who underwent fundoplication, the risk of gastroesophageal reflux disease (GERD) was reduced as compared to patients who did not undergo fundoplication (RR: 0.64, 95% CI: 0.40-1.04, p = 0.069, I2 = 47.2%). A similar trend was also observed in recurrence (RR: 0.53, 95% CI: 0.27-1.03, p = 0.061, I2 = 0.0%) and reoperations (RR: 0.25, 95% CI: 0.02-2.69, p = 0.25, I2 = 56.7%). However, patients who underwent fundoplication had an increased risk of dysphagia (RR: 1.68, 95% CI: 0.59-4.81, p = 0.83, I2 = 42%). CONCLUSIONS: There is a higher rate of recurrence of gastroesophageal reflux disease, recurrence of hernia and reoperation when no fundoplication is performed during a paraesophageal hernia repair but a lower risk of dysphagia, but none of these reached statistical significance.(Comment 1) Paraesophageal hernia repair with fundoplication should be performed, but it is acceptable to not do it in certain situations.

Biocompatibility Study of a Commercial Printed Circuit Board for Biomedical Applications: Lab-on-PCB for Organotypic Retina Cultures.

Printed circuit board (PCB) technology is well known, reliable, and low-cost, and its application to biomedicine, which implies the integration of microfluidics and electronics, has led to Lab-on-PCB. However, the biocompatibility of the involved materials has to be examined if they are in contact with biological elements. In this paper, the solder mask (PSR-2000 CD02G/CA-25 CD01, Taiyo Ink (Suzhou) Co., Ltd., Suzhou, China) of a commercial PCB has been studied for retinal cultures. For this purpose, retinal explants have been cultured over this substrate, both on open and closed systems, with successful results. Cell viability data shows that the solder mask has no cytotoxic effect on the culture allowing the application of PCB as the substrate of customized microelectrode arrays (MEAs). Finally, a comparative study of the biocompatibility of the 3D printer Uniz zSG amber resin has also been carried out.

Semi-Automatic Lab-on-PCB System for Agarose Gel Preparation and Electrophoresis for Biomedical Applications.

In this paper, a prototype of a semi-automatic lab-on-PCB for agarose gel preparation and electrophoresis is developed. The dimensions of the device are 38 × 34 mm2 and it includes a conductivity sensor for detecting the TAE buffer (Tris-acetate-EDTA buffer), a microheater for increasing the solubility of the agarose, a negative temperature coefficient (NTC) thermistor for controlling the temperature, a light dependent resistor (LDR) sensor for measuring the transparency of the mixture, and two electrodes for performing the electrophoresis. The agarose preparation functions are governed by a microcontroller. The device requires a PMMA structure to define the wells of the agarose gel, and to release the electrodes from the agarose. The maximum voltage and current that the system requires are 40 V to perform the electrophoresis, and 1 A for activating the microheater. The chosen temperature for mixing is 80 ∘C, with a mixing time of 10 min. In addition, the curing time is about 30 min. This device is intended to be integrated as a part of a larger lab-on-PCB system for DNA amplification and detection. However, it can be used to migrate DNA amplified in conventional thermocyclers. Moreover, the device can be modified for preparing larger agarose gels and performing electrophoresis.

Long Term Outcomes after Laparoscopic Assisted Trans-Gastric Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND: The gastric bypass is a commonly performed bariatric procedure. The stomach is divided into a small pouch as well as leaving a larger remnant that is bypassed by the gastrojejunal anastomosis. This makes access to the biliary system difficult as an endoscope cannot transverse the esophagus, roux limb, and biliopancreatic limb. Therefore, a transgastric approach (endoscopic retrograde cholangiopancreatography [t-ERCP]) through the abdominal wall and remnant stomach is necessary. This involves the surgical team providing access to the remnant stomach for the gastroenterologist to perform the t-ERCP. We have performed a number of these for biliary pathology that ranges from cancer to retained gallstones. We evaluated these patients with at least a 3-year follow-up to determine long term outcomes. METHODS: We conducted a chart review of patients who underwent a t-ERCP with at least a 3-year follow-up. We collected de-identified data including demographics, operative details, complications, and postoperative courses. RESULTS: There were 12 patients who underwent t-ERCP. Eleven patients had at least a 3-year follow-up with a mean follow-up of 68.1 months (excluding one death from pancreatic cancer). The most common pathology was benign biliary stricture (n = 6), followed by retained gallstones (n = 4), with one pancreatic cancer, and one normal examination. Two patients still had epigastric pain at long term follow-up after 3 years. CONCLUSION: T-ERCP is safe and efficacious with good long-term results.

Reluctance in duodenal switch adoption: an international survey among bariatric surgeons.

BACKGROUND: Duodenal switch (DS) still comprises less than 1% of the overall primary procedures in the United States. Our aim is to explore the reasons behind surgeons' reluctance to DS adoption. OBJECTIVES: To determine perceived reasons for the widespread lack of adoption of the DS. SETTING: Worldwide survey of closed bariatric surgery social media groups. METHODS: A standardized questionnaire was posted on 2 closed social media bariatric groups. DS was used as an umbrella term that includes traditional BPD with duodenal switch, single anastomosis duodeno-ileostomy (SADI) and loop DS. The questionnaire link was accessible to bariatric surgeons only for a period of 1 week. RESULTS: Survey responses (n = 193) were analyzed. The majority (75%) were fellowship-trained bariatric surgeons, and 58% were practicing in the United States. Although 72.9% believed DS to be a good bariatric procedure, it was not being performed by 64% of the respondents. The main reasons behind DS nonadoption included a perceptible high long-term complication rate (43.5%), lack of training (38.1%), and procedure seldomly demanded by patients (31.5%). For surgeons who perform DS, 16.4% use it as a revisional procedure, mainly following sleeve gastrectomy (40.5%). Finally, 29.5% of surgeons believed that the American Society of Metabolic and Bariatric Surgery endorsement of SADI will encourage them to add DS to their practice. They are mostly planning to do so by visiting other surgeons and getting proctored (42.6%). CONCLUSION: This survey will help guide bariatric societies and governing bodies in addressing the issues and concerns preventing surgeons from adopting DS in their practice by elucidating the chief reasons and circumstances behind this occurrence.

Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down's syndrome mouse model.

Down syndrome (DS) is the most frequent genetic cause of intellectual disability including hippocampal-dependent memory deficits. We have previously reported hippocampal mTOR (mammalian target of rapamycin) hyperactivation, and related plasticity as well as memory deficits in Ts1Cje mice, a DS experimental model. Here we characterize the proteome of hippocampal synaptoneurosomes (SNs) from these mice, and found a predicted alteration of synaptic plasticity pathways, including long term depression (LTD). Accordingly, mGluR-LTD (metabotropic Glutamate Receptor-LTD) is enhanced in the hippocampus of Ts1Cje mice and this is correlated with an increased proportion of a particular category of mushroom spines in hippocampal pyramidal neurons. Remarkably, prenatal treatment of these mice with rapamycin has a positive pharmacological effect on both phenotypes, supporting the therapeutic potential of rapamycin/rapalogs for DS intellectual disability.

CPEB1 is overexpressed in neurons derived from Down syndrome IPSCs and in the hippocampus of the mouse model Ts1Cje.

Trisomy 21, also known as Down syndrome (DS), is the most frequent genetic cause of intellectual impairment. In mouse models of DS, deficits in hippocampal synaptic plasticity have been observed, in conjunction with alterations to local dendritic translation that are likely to influence plasticity, learning and memory. Here we show that expression of a local translational regulator, the Cytoplasmic Polyadenylation Element Binding Protein 1 (CPEB1), is enhanced in hippocampal neurons from the Ts1Cje DS mouse model. Interestingly, this protein, which is also involved in dendritic mRNA transport, is overexpressed in dendrites of neurons derived from DS human induced pluripotent stem cells (hIPSCs). Moreover, there is an increase in the mRNA levels of α-Calmodulin Kinase II (α-CaMKII) and Microtubule-associated protein 1B (MAP1B), two dendritic mRNAs, in Ts1Cje synaptoneurosomes. Taking into account the fundamental role of CPEB1 protein and its target mRNAs in synaptic plasticity, these data could be relevant to the intellectual impairment in the context of DS.

El arco facial en la elaboración de las férulas oclusales tipo Míchigan / Face bows in the production of Michigan occlusal splints

Introducción: la férula oclusal tipo Míchigan (FOM) es un dispositivo usado frecuentemente para el manejo de pacientes con bruxismo. La literatura menciona el uso del arco facial para el montaje de modelos en el articulador semiajustable, sin embargo el beneficio de este en la elaboración de las FOM aún es controvertido. Por lo tanto el objetivo de esta investigación fue comparar el registro de número de puntos de contacto y el tiempo de ajuste entre las FOM elaboradas con y sin el uso del arco facial en pacientes con diagnóstico de bruxismo. Métodos: se elaboraron 90 férulas entregadas a 45 pacientes de la Clínica de Rehabilitación Benemérita Universidad Autónoma de Puebla (BUAP), previo diagnóstico de bruxismo. Las dos férulas elaboradas (una con modelos montados con arco facial y otra sin él), se compararon en el articulador y clínicamente. Se registró el número de puntos de contacto obtenidos en ambas férulas y el tiempo de ajuste requerido. Las comparaciones se hicieron con la prueba estadística de Wilcoxon y significancia menor a 0,05. Resultados: la media de puntos de contacto en boca de las férulas con el uso del arco fue superior (11,67) a la de sin uso del arco (11,58) sin diferencias significativas (p = 0,799). El tiempo de ajuste fue superior en las férulas elaboradas sin arco (51 s) que con arco (33 s), sin diferencias significativas (p = 0,332). Conclusión: no existen diferencias significativas con el uso del arco facial o sin él para la elaboración de las FOM en pacientes bruxómanos.

Introduction: Michigan occlusal splints (MOS) are frequently used for the management of patients with bruxism. The literature mentions the use of face bows for mounting models in semi-adjustable articulators, but its benefit in the production of MOS is still controversial. Therefore, the objective of this study was to compare the record of number of contact points and mounting time between MOS made with and without face bows in patients diagnosed with bruxism. Methods: a total of 90 splints were made and distributed among 45 patients diagnosed with bruxism at the Oral Rehabilitation Clinic of Benemérita Universidad Autónoma de Puebla (BUAP). The two splints (one made with a face bow mounted model and the other one without it) were compared at the articulator and clinically. The number of obtained contact points was recorded in both splints as well as the time needed for mounting. The comparisons were made with Wilcoxon statistical test and a significance level lower than 0.05. Results: the splints with face bows showed a greater average of contact points in the mouth (11.67) compared with the ones without face bows (11.58), with no significant difference (p = 0.799). Mounting time was higher in the splints made without face bows (51 s) compared with the ones with face bows (33 s), with no significant difference (p = 0.332). Conclusion: there are no significant differences in using face bows for developing MOS in bruxism patients.