Impact of siRNA-Mediated Cofilin-1 Knockdown and Obesity Associated Microenvironment on the Motility of Natural Killer Cells.

The anti-tumor capacity of natural killer (NK) cells heavily relies on their ability to migrate towards their target cells. This process is based on dynamic actinrearrangement, so-called actin treadmilling, andis tightly regulated by proteins such as cofilin-1. The aim of the present study was to identify the role of cofilin-1 (CFL-1) in the migratory behavior of NK cells and to investigate a possible impact of an obesity-associated micromilieu on these cells, as it is known that obesity correlates with various impaired NK cell functions. CFL-1 was knocked-down via transfection of NK-92 cells with respective siRNAs. Obesity associated micromilieu was mimicked by incubation of NK-92 cells with adipocyte-conditioned medium from human preadipocyte SGBS cells or leptin. Effects on CFL-1 levels, the degree of phosphorylation to the inactive pCFL-1 as well as NK-92 cell motility were analyzed. Surprisingly, siRNA-mediated CFL-1 knockdown led to a significant increase of migration, as determined by enhanced velocity and accumulated distance of migration. No effect on CFL-1 nor pCFL-1 expression levels, proportion of phosphorylation and cell migratory behavior could be demonstrated under the influence of an obesity-associated microenvironment. In conclusion, the results indicate a significant effect of a CFL-1 knockdown on NK cell motility.

Extended arc of rotation of Latissimus Dorsi Musculocutaneous Flap providing well-vascularized tissue for reconstruction of complete defects of the sternum: An anatomical study of flap pedicle modification.

BACKGROUND: Deep sternal wound infections (DSWI) following cardiothoracic surgery represent a life quality endangering sequelae and may lead to sternal osteomyelitis. Radical debridement followed by Negative Pressure Wound Therapy (NPWT) may achieve infection control, provide angiogenesis, and improve respiratory function. When stable wound conditions have been established a sustainable plastic surgical flap reconstruction should be undertaken. OBJECTIVE: This study analyses a method to simplify defect coverage with a single Latissimus Dorsi Myocutaneous Flap (LDMF). METHODS: Preparation of 20 LDMF in ten fresh frozen cadavers was conducted. Surgical steps to increase pedicle length were evaluated. The common surgical preparation of LDMF was compared with additional transection of the Circumflex Scapular Artery (CSA). RESULTS: Alteration of the surgical preparation of LDMF by sacrificing the CSA may provide highly valuable well-vascularized muscle tissue above the sensitive area of the Xiphisternum. All defects could be completely reconstructed with a single LDMF. The gain in length of flap tissue in the inferior third of the sternum was 3.86±0.9 cm (range 2.2 to 8 cm). CONCLUSIONS: By sacrificing the CSA in harvesting the LDMF a promising gain in length, perfusion and volume may be achieved to cover big sternal defects with a single flap.

Open vs Minimally Invasive Resection of the First Metatarsocuneiform Joint: An Anatomical Study.

BACKGROUND: The modified Lapidus arthrodesis is a standard procedure to correct middle to severe hallux valgus (HV) deformities. Recently, minimally invasive techniques of first metatarsocuneiform joint (MCJ) resection using a Shannon burr were described. The primary goal of this study is to compare the anatomical efficacy and safety of first MCJ resection using a straight 2 × 13-mm Shannon burr and minimally invasive technique (MIS) vs an open technique using an oscillating saw. METHODS: Ten pairs of fresh frozen cadaveric feet were randomly assigned to open or MIS first MCJ resection with subsequent systematic dissection. For the MIS procedure, a dorsomedial approach was used and for the open procedure a medioplantar approach was used. Cartilage removal was investigated by analyzing standardized scaled photographs of the resected articular surfaces with ImageJ software. Nearby structures at risk were analyzed for iatrogenic violation: tibialis anterior (TA), extensor hallucis longus (EHL) and peroneus longus (PL) tendons, and the Lisfranc ligament complex (LLC). RESULTS: In the MIS group, the median cartilage resection was 85.9% at the cuneiform and 85.6% at the metatarsal bone compared to 100% cartilage resection in open technique (P < .01). Iatrogenic damage of the LLC, EHL, and TA tendons was not found in any group. The PL tendon was thinned out (<25% of tendon thickness) in 4 cases (40%) in the open group and in 1 case (10%) in the MIS group. A safe zone of 3.0 mm between the articular surface of the cuneiform bone and the LLC was identified, which can be resected without putting the LLC at risk when performing lateral-based wedge resections. CONCLUSION: In this cadaver study with the procedures performed by an experienced foot and ankle surgeon, and using 2 different surgical approaches, we found general parity between the Shannon burr MIS technique vs oscillating saw open technique techniques with more risk to the PL with our open technique and approximately 15% less cartilage resection with our MIS technique. LEVEL OF EVIDENCE: Level V, cadaver study.

Health profession students' outlooks on the medical profession during the COVID-19 pandemic: a global perspective.

BACKGROUND: This article summarizes a global study of the effect of the COVID-19 pandemic on junior health professions students' outlook on medicine. The pandemic has significantly affected health professions education. There is limited understanding of how students' pandemic experiences will affect them, and what impact these events may have on their career paths or the future of the professions. This information is important as it impacts the future of medicine. METHODS: In the Fall 2020 semester, 219 health professions students at 14 medical universities worldwide responded to the question: 'Has this experience (with COVID-19) changed your outlook on medicine as a profession?'. Short essay responses were semantically coded and organized into themes and subthemes using an inductive approach to thematic analysis. RESULTS: 145 responses were submitted. Themes were identified: (1) students reflected on the interaction between politics and healthcare; (2) reported becoming more aware of the societal expectations placed on healthcare professionals, including undertaking high risks and the sacrifices that healthcare professionals must make; (3) found reassurance from the recognized importance of healthcare professionals and expressed pride to be entering the profession; and (4) reflected on the current state of healthcare, including its limitations and future. CONCLUSION: Most students, independent of the extent of the pandemic in their respective countries, noted a change in their outlook regarding medicine. An overall positive outlook was noted in most junior students. Educators need to work on nurturing these sentiments and attitudes to help young students maintain a healthy relationship towards their chosen profession.

Prenatal exposure to opioids and neurodevelopment in infancy and childhood: A systematic review.

Aim: This systematic review aims to estimate the relationship between prenatal exposure to opioids and neurodevelopmental outcomes and examines potential sources of heterogeneity between the studies. Methods: We searched four databases through May 21st, 2022: PubMed, Embase, PsycInfo and the Web of Science according to a specified search strings. Study inclusion criteria include: (1) cohort and case-control peer-reviewed studies published in English; (2) studies comparing neurodevelopmental outcomes among children with prenatal opioid-exposure (prescribed or used non-medically) vs. an unexposed group. Studies investigating fetal alcohol syndrome or a different primary prenatal exposure other than opioids were excluded. Two main performed data extraction using "Covidence" systematic review platform. This systematic review was conducted in accordance with PRISMA guidelines. The Newcastle-Ottawa-Scale was used for quality assessment of the studies. Studies were synthesized based on the type of neurodevelopmental outcome and the instrument used to assess neurodevelopment. Results: Data were extracted from 79 studies. We found significant heterogeneity between studies due to their use of different instruments to explore cognitive skills, motor, and behavioral outcomes among children of different ages. The other sources of heterogeneity included: procedures to assess prenatal exposure to opioids; period of pregnancy in which exposure was assessed; type of opioids assessed (non-medical, medication used for opioid use dis-order, prescribed by health professional), types of co-exposure; source of selection of prenatally exposed study participants and comparison groups; and methods to address lack of comparability between exposed and unexposed groups. Cognitive and motor skills as well as behavior were generally negatively affected by prenatal opioid exposure, but the significant heterogeneity precluded a meta-analysis. Conclusion: We explored sources of heterogeneity in the studies assessing the association between prenatal exposure to opioids and neurodevelopmental outcomes. Sources of heterogeneity included different approaches to participant recruitment as well as exposure and outcome ascertainment methods. Nonetheless, overall negative trends were observed between prenatal opioid exposure and neuro-developmental outcomes.

A thematic analysis of students' discussions on death and body donation in international online focus groups.

Historically, Anatomy education is an in-person discipline involving exposure to human body donors that facilitates personal and professional growth through, in part, the initiation of reflection on the topic of death. However, during the COVID-19 pandemic the decreased exposure to cadaveric anatomy for many health professions students may have influenced the depth of their individual reflections on this topic. Accordingly, this study aimed to investigate the effect of an alternate approach-focus group discussions between peers with varying degrees of exposure to cadaveric material-that may offer one strategy to stimulate deep reflection on the topic of death. A programmatic intervention was introduced, wherein students (n = 221) from 13 international universities discussed differences in their anatomy courses during small focus group sessions as part of an online exchange program. An inductive semantic thematic analysis was conducted on responses to an open-ended text-response question on how the activity influenced students' reflections about death. Resulting themes were organized into categories that described the content and topics of the students' discussions as they grappled with this sensitive topic. The students reportedly engaged in deep reflection and expressed an increased sense of connectedness with their peers, despite their disparate exposure levels to cadaveric anatomy and being physically distanced. This demonstrates that focus groups with students experiencing different laboratory contexts can be used to help all students reflect on the topic of death and that interchanges between dissecting and non-dissecting students can initiate thoughts about death and body donation among non-dissecting students.

Fibula Nail versus Locking Plate Fixation-A Biomechanical Study.

In the treatment of ankle fractures, complications such as wound healing problems following open reduction and internal fixation are a major problem. An innovative alternative to this procedure offers a more minimally invasive nail stabilization. The purpose of this biomechanical study was to clarify whether this method was biomechanically comparable to the established method. First, the stability (range of motion, diastasis) and rotational stiffness of the native upper ankle were evaluated in eight pairs of native geriatric specimens. Subsequently, an unstable ankle fracture was created and fixed with a locking plate or a nail in a pairwise manner. The ankles showed significantly less stability and rotational stiffness properties after nail and plate fixations than the corresponding native ankles (p < 0.001 for all parameters). When comparing the two methods, both showed no differences in their range of motion (p = 0.694) and diastasis (p = 0.166). The nail also presented significantly greater rotational stiffness compared to the plate (p = 0.001). However, both fixations remained behind the native stability and rotational stiffness. Due to the comparable biomechanical properties of the nail and plate fixations, an early weight-bearing following nail fixation should be assessed on a case-by-case basis considering the severity of fractures.

Fetal Development in Anatomical Preparations of Ruysch and the Meckels in Comparison.

Anatomical collections have been used for centuries for research and teaching purposes. By the example of selected preparations of fetal development from the Ruysch collection (17th-18th centuries) and the Meckel collections (18th-19th century), this article aims to trace the changing purposes, specifics and methods of creating specimens as well as the development of anatomy during that period. The selected specimens are compared and analyzed implementing the historical-critical method. Regarding the appearance of the preparations, we see a transition from the visually aesthetic specimens (Ruysch) to exact ones (Meckel collections). If Ruysch's preparations were compared in his time to works of art, specimens created by three anatomists of the Meckel dynasty were primarily created for teaching and research purposes. However, Ruysch's preparations tracing fetal circulation were scientific discoveries of the time. As for preparations of fetal development from the Meckel collections, we see both specimens of physiological processes already known at that time and experimental ones. Regarding teratology, Ruysch and Meckel the Younger tried to explain malformations, but their anatomical preparations could hardly give answers to the cause of deviations from the norm. The differences between the collections can be explained by the different stages of development of anatomy of the time and by the research interests of the anatomists themselves.

The Anatomy Course During COVID-19: The Impact of Cadaver-Based Learning on the Initiation of Reflection on Death.

Background: During the COVID-19 pandemic, in-person cadaveric dissection laboratories for teaching anatomy were omitted by many schools around the world. While knowledge domains can be easily evaluated via remote exams, non-traditional discipline-independent skills such as those encouraged through reflection on the topic of death are often overlooked. This study investigated how different anatomy course formats played a role in initiating students' reflections on death during the COVID-19 pandemic. Method: In fall 2020, 217 medical, dental, premedical, and health sciences students from 13 international universities discussed differences in their anatomy courses online. Formats of anatomy courses ranged from dissection-based, prosection-based, hybrid (combination of dissection and prosection) to no laboratory exposure at all. Students' responses to the question, "Did/does your anatomy course initiate your thinking about life's passing?" were collected, and they self-reported themes that were present in their reflections on death using a multiple-choice prompt. Statistical analyses to detect differences between students with and without exposure to cadavers were performed using the chi-squared test. Results: When comparing students who had exposure to human anatomical specimens to those who had no exposure, the majority of students with exposure thought that the course did initiate thoughts about life's passing, compared to students without exposure (P < 0.05). Reflection themes were consistent across groups. Discussion: These findings indicate that anatomy dissection courses are important for the initiation of students' feelings about the topic of death. Omission of cadaveric dissection- or prosection-based laboratories will decrease the likelihood that students initiate reflection on this topic and gain important transferable skills.

Investigation of Behavior and Plasma Levels of Corticosterone in Restrictive- and Ad Libitum-Fed Diet-Induced Obese Mice.

Diet-induced obesity (DIO) mice models are commonly used to investigate obesity-related health problems. Until now, only sparse data exist on the influence of DIO on behavior and stress hormones in mice. The present study investigates high-fat DIO with two different feeding regimes on behavioral parameters in mice. Various behavioral tests (open field, elevated plus maze, social interaction, hotplate) were performed with female BALB/c and male C57BL/6 mice after a feeding period of twelve weeks (restrictive vs. ad libitum and normal-fat diet vs. high-fat diet) to investigate levels of anxiety and aggression. BALB/c mice were DIO-resistant and therefore the prerequisite for the behavior analyses was not attained. C57BL/6 mice fed a high-fat diet had a significantly higher body weight and fat mass compared to C57BL/6 mice fed a control diet. Interestingly, the DIO C57BL/6 mice showed no changes in their aggression- or anxiety-related behavior but showed a significant change in the anxiety index. This was probably due to a lower activity level, as other ethological parameters did not show an altered anxiety-related behavior. In the ad libitum-fed DIO group, the highest corticosterone level was detected. Changes due to the feeding regime (restrictive vs. ad libitum) were not observed. These results provide a possible hint to a bias in the investigation of DIO-related health problems in laboratory animal experiments, which may be influenced by the lower activity level.

Evaluation of the ideal length of the Seldinger needle for internal jugular vein catheter placement.

Placement of central venous catheters (CVC) into the internal jugular vein represents a routine clinical intervention. The periprocedural complication rate ranges from 5 to 20% and can be reduced by ultrasound guidance, training of residents and other measures. We aimed to proof that the average Seldinger needle is too long, increasing the risk of periprocedural injury, best epitomized in the stellate ganglion injury/irritation. The first part of the study was an online market analysis to investigate the standard needle length currently offered as part of the CVC placement sets. The second part of the study involved 35 hospitalized patients (14 female; median age 74.5 years). In those the distance between the skin and the internal jugular vein as well as the diameter of the internal jugular vein was measured by ultrasound in both, supine position as well as 45° semi-sitting position. In the third part of the study 80 body donors (45 female; median age 83.0 years) preserved by the ethanol/formaldehyde method were studied. In those the distance and angle between the typical landmark for insertion of the Seldinger needle for internal jugular vein catheter placement to the stellate ganglion was measured. The median [interquartile range] Seldinger needle length was 7 [4.0-10.0] cm. In the examined patients the maximum distance between the skin and the internal jugular vein was 1.87 cm. The minimum distance was 0.46 cm and the median distance averaging supine and 45° position was 1.14 [0.94-1.31] cm. Regarding the body donors the median distance from the insertion point of the internal jugular vein to the stellate ganglion was longer in men 5.5 [4.95-6.35] cm than in women 5.2 [4.7-5.9] (p = 0.031 unpaired t-test). With 7 cm average length the Seldinger needle currently sold as part of CVC sets is long enough to physically reach the stellate ganglion, not to mention more proximal structures. A shorter needle length would be sufficient to reach the internal jugular vein even in obese patients and with a small insertion angle while minimizing the possibility to cause severe injury as structures like the pleura and the stellate ganglion could not be reached by shorter needles.

Obesity, colorectal cancer and MACC1 expression: A possible novel molecular association.

Obesity is a major and increasing public health concern, associated with an increased risk of and mortality from several types of cancer including colorectal cancer (CRC), being associated with cancer progression, metastasis and resistance to therapy. It was hypothesized that the expression of cancer/metastasis­inducing gene metastasis­associated in colon cancer 1 (MACC1) is increased in obesity, which may constitute a link to obesity­induced cancer. The present study thus analyzed circulating cell­free plasma MACC1 expression levels in human obese (vs. normal weight) adult individuals from independent studies, namely the Martin Luther University (MLU) study (n=32) and the Metabolic syndrome study (MetScan, Berlin) (n=191). Higher plasma MACC1 levels were found in obese individuals, increasing with a greater body fat mass and body mass index; these levels were predominantly observed in male and to a lesser extent in female individuals, although the results were not significant. A reduction in body fat mass following dietary intervention and physical exercise decreased the MACC1 expression levels in the MLU study. Furthermore, Wistar rats with diet­induced obesity exhibited slightly increased plasma MACC1 levels compared with rats of normal weight. The obese Wistar rats exposed to azoxymethane to induce colon cancer exhibited a more severe colon tumor outcome, which was associated with significantly increased MACC1 levels compared with their non­obese littermates. On the whole, the findings of the present study suggest an association between MACC1 and obesity, as well as with obesity­induced CRC.

Microimaging of a novel intracochlear drug delivery device in combination with cochlear implants in the human inner ear.

The effective delivery of drugs to the inner ear is still an unmet medical need. Local controlled drug delivery to this sensory organ is challenging due to its location in the petrous bone, small volume, tight barriers, and high vulnerability. Local intracochlear delivery of drugs would overcome the limitations of intratympanic (extracochlear) and systemic drug application. The requirements for such a delivery system include small size, appropriate flexibility, and biodegradability. We have developed biodegradable PLGA-based implants for controlled intracochlear drug release that can also be used in combination with cochlear implants (CIs), which are implantable neurosensory prosthesis for hearing rehabilitation. The drug carrier system was tested for implantation in the human inner ear in 11 human temporal bones. In five of the temporal bones, CI arrays from different manufacturers were implanted before insertion of the biodegradable PLGA implants. The drug carrier system and CI arrays were implanted into the scala tympani through the round window. Implanted temporal bones were evaluated by ultra-high-resolution computed tomography (µ-CT) to illustrate the position of implanted electrode carriers and the drug carrier system. The µ-CT measurements revealed the feasibility of implanting the PLGA implants into the scala tympani of the human inner ear and co-administration of the biodegradable PLGA implant with a CI array.

Minimally invasive hallux valgus correction with Internal Hallux Fixator® - A comparative cadaver study.

BACKGROUND: The Internal Hallux Fixator® (IHF®; Waldemar Link, Hamburg, Germany) was designed for open surgical hallux valgus correction. It allows a defined lateralisation of the first metatarsal head after V-shaped, Chevron-like distal metatarsal osteotomy in order to correct mild to middle hallux valgus deformities. The intramedullary fixation provides dynamic compression of the osteotomy and thus postoperative full weight bearing mobilization is an integral part of the therapy. This comparative cadaver model study investigates the feasibility of implanting the device using a minimally invasive technique and compares its capability of first metatarsal head lateralisation to the established 3rd generation MICA (Minimally Invasive Chevron and Akin osteotomy) technique. METHODS: 16 fresh frozen cadaveric feet (8 left, 8 right) of 8 body donors received either MICA (Group 1), or an IHF® in a minimally invasive technique (Group 2). The achievable first metatarsal head lateralisation and operating time were measured and pitfalls recorded. RESULTS: This cadaver model study confirmed, the minimally invasive implantation of the Internal Hallux Fixator® can be performed reliably via 10 mm mini incision with V-shaped distal metatarsal osteotomy. The mean first metatarsal head lateralisation was comparable between the groups with no statistically significant difference (7.2 (±1.9) mm in G1, or 8.3 (±0.8) mm in G2; p = 0.09). The IHF® was inserted and fixed in mean 3.7 (±0.6) min, whereas double screw fixation needed 10 (±3.7) min. LEVEL OF CLINICAL EVIDENCE: 5, Cadaver model study.

Infants' prenatal exposure to opioids and the association with birth outcomes: A systematic review and meta-analysis.

BACKGROUND: Prenatal exposure to opioids (PEO) is a worldwide public health issue. Opioids cross the placental barrier and may affect the developing foetus and the birth outcomes. OBJECTIVES: This review aimed to explore newborns' weight, length and head circumference, preterm birth, and perinatal death as primary outcomes in relation to PEO. The secondary outcomes were gestational age at birth, Apgar scores and length of hospitalisation after delivery. DATA SOURCES: PubMed, Embase, PsycInfo and the Web of Science. STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria were (i) cohort, case-control or cross-sectional peer-reviewed studies published in English through 1 March 2021; (ii) comparing outcomes between prenatal exposed and unexposed groups to opioids (prescribed or obtained illegally). Exclusion criteria were foetal alcohol syndrome and non-opioid primary exposure. SYNTHESIS: Data were extracted by two authors. The Newcastle-Ottawa Quality Assessment Scale was used for study quality assessment. Due to heterogeneity across studies, we used random effects models to obtain pooled standardised mean difference (SMD), pooled risk ratio (RR) and 95% confidence interval (CI). RESULTS: Data from 80 studies were extracted. In meta-analyses, opioid-exposed neonates had lower birthweight (SMD -0.77, 95% CI -0.90, -0.64, I2  = 82%), smaller head circumference (SMD -0.67, 95% CI -0.86, -0.48, I2  = 84%), shorter birth length (SMD -0.97, 95% CI -1.24, -0.70, I2  = 91%) and gestational age (SMD -0.45, 95% CI -0.60, -0.30, I2  = 80%) than unexposed neonates. Pooled risks of neonatal death and preterm birth were higher among opioid-exposed compared to unexposed neonates (RR 4.05, 95% CI 2.12, 7.72, I2  = 73%; and RR 1.92, 95% CI 1.57, 2.35, I2  = 99%). CONCLUSIONS: We found increased risks of adverse birth outcomes in relation to PEO. Caution should be used in interpreting the findings, as many studies were rated as poor quality, and with substantial inter-study heterogeneity. Future studies should ensure comparability of opioid-exposed and -unexposed group to strengthen internal validity.

Variability in the distance from the end of the gray matter to the end of the conus medullaris: a case-triggered histological investigation.

OBJECTIVE: The background for this investigation was the dramatic course of a 14-year-old girl with a spontaneous hemorrhage in the area of the conus medullaris resulting in a complete cross-sectional syndrome with bladder and bowel dysfunction. Despite immediate surgical treatment, the patient showed close to no postoperative improvement. Subsequent histopathological examination of the removed masses revealed a cavernoma. To better understand the link between the site and symptoms of conus medullaris lesions, the authors performed a literature search and then histological examination of the conus medullaris of 18 cadaveric specimens from body donors. METHODS: After a literature search regarding the histological features of the structure of the conus medullaris did not lead to satisfying results, the authors performed histological examination of the conus medullaris in 18 cadaveric specimens from body donors. The largest (a) and smallest (b) diameters of the conus medullaris were measured, noting individual variations in the distance from the caudal ending of the gray matter to the macroscopically visible end of the conus medullaris. Correlations of these differences with sex, body height, gray matter transverse diameter, and cross-sectional area at the end of the gray matter were analyzed. RESULTS: Gray matter displayed in the form of a butterfly figure was found along almost the entire length of the conus medullaris. The specific slide containing the end of the gray matter was noted. The distance between the caudal ending of the gray matter in the conus and the macroscopical end of the conus medullaris was defined as the gray matter to cone termination (GMCT) distance. There were great individual variations in the distance from the caudal ending of the gray matter to the macroscopically visible end of the conus medullaris. Analysis of the correlations of these differences with sex, body height, gray matter transverse diameter, and cross-sectional area at the end of the gray matter showed no significant sex-specific differences in the GMCT distance. Patient body height and transverse diameter at the end of the gray matter were found to be correlated positively with the GMCT distance. Moreover, greater height also correlated positively with the cross-sectional area at the end of the gray matter. CONCLUSIONS: This report is, to the authors' knowledge, the first published description of the histological structure of the conus medullaris and can serve as the basis for a better understanding of neurological deficits in patients with a conus medullaris syndrome. Findings that gray matter can be detected far into the conus medullaris, with large individual differences in the endpoint of the gray matter, are important for operative care of intramedullary masses and vascular malformations in this area. It is therefore important to use electrophysiological monitoring during these operations.

The Impact of High-Fat Diet and Restrictive Feeding on Natural Killer Cells in Obese-Resistant BALB/c Mice.

Background: The association of obesity and an increased risk for severe infections and various cancer types is well-described. Natural killer (NK) cells are circulating lymphoid cells and promoters of the immune response toward viruses and malignant cells. As demonstrated in previous studies the phenotype and functionality of NK cells is impaired in obesity. So far, the majority of animal studies were exclusively performed using ad libitum feeding regimes and it remained unclear whether NK cell alterations are mediated by obesity-associated immunological changes or by direct effects of the dietary composition. Therefore, the aim of the present study was to characterize NK cells in the peripheral blood of obese-resistant BALB/c mice supplied a normal-fat diet (NFD) or high-fat diet (HFD), ad libitum or in a restrictive manner. Methods: Twenty-eight BALB/c-mice were fed a NFD or HFD either ad libitum or in a restrictive feeding regime with 90% of the mean daily diet supply of the corresponding ad libitum group (each group n = 7). Blood and visceral adipose tissue were collected for flow cytometric analysis, analysis of plasma cytokine concentrations by multiplex immunoassay and real-time RT-PCR analyses. For statistical analyses two-way ANOVA with the factors "feeding regime" and "diet" was performed followed by a post-hoc Tukey's multiple comparison test and to compare means of the four mouse groups. Results: Ad libitum-feeding of a HFD in BALB/c mice has no influence on body weight gain, visceral fat mass, plasma cytokine concentrations, immune cell populations as well as the number, frequency and phenotype of NK cells. In contrast, restrictive feeding of a HFD compared to NFD led to significantly higher body weights, visceral fat mass and plasma interferon-γ concentrations which was associated with changes in the frequencies of granulocytes and NK cell subsets as well as in the surface expression of NK cell maturation markers. Conclusion: Results demonstrate for the first time that HFD-induced alterations in NK cells are consequences of the obese associated immunological profile rather than a direct effect of the dietary composition. These data can help to clarify the increased risk for cancer and severe infections in obesity.

Alternatives to Student Outbound Mobility-Improving Students' Cultural Competency Skills Online to Improve Global Health Without Travel.

Introduction: Student outbound mobility is a major element in internationalization of medical education and global health education. However, this approach is often criticized, as it is inherently inequitable. Internationalization at home is a newer concept that aims to provide students with international skills and experiences without exchange travel. We report detailed outcomes of an international online program during the COVID-19 pandemic, which aimed to include acquisition of cultural awareness and competency-similar to what the students would have obtained if they had travelled abroad. Method: Sixty-eight students from 12 international universities participated in international small peer group collaborative work, and online networking. Perceived improvement of cultural competency using Likert scale and open-ended questions was used as a measure of success. Furthermore, students' definition of cultural competency in the different countries was obtained. Results: Students improved their cultural competency skills. Data analysis supported statistically significant improvement of the above skills after the program, in comparison to the start of the program. Discussion: Internationalization of medical education can be achieved at home-via structured online peer exchanges-and can provide students with intercultural skills and networking opportunities that are typically achieved via international in-person travel. The above represents a socially just and equitable way to reach all students and can result in improvement of their cultural competency, preparing them for their work in global health, and thereby resulting in improvement of global health. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-021-01332-9.

Initiating Students' Reflections on Life's Passing in the Anatomy Course - an International Observation at 14 Universities.

BACKGROUND: Medical and dental students' feelings and thoughts about the topic of death and life's passing are often associated with learning in the gross anatomy course, when students begin working with a deceased body donor in order to study human anatomy. Little is known of whether the format of anatomy teaching has an impact on these experiences. An observational study was performed to capture the initiation of students' sentiments on the topic of life's passing during the anatomy course at 14 international universities, identify common themes regarding these thoughts, and to study the connection to variations in anatomy course formats and included elements. METHOD: Preclinical anatomy students reflected on one question (i.e., "How did your experience in the anatomy laboratory bring about your reflections on the meaning of life and human existence as well as the sanctity of one's passing?"). Written assignments were collected and anonymously coded. Information on anatomy courses was obtained via faculty questionnaires. RESULT: A variety of themes were identified at the different schools, correlated with different anatomy formats and elements. Results indicate that the courses that offer hands-on cadaveric dissections may play an important role in triggering these sentiments. DISCUSSION: The initiation of students' sentiments about the topic of death varies and includes several themes. There can be a connection to the way anatomy is taught, particularly if hands-on comprehensive cadaveric dissection or prosections are included. CONCLUSION: In summary, anatomy courses can initiate students' thinking about life's passing - particularly in schools that offer hands-on cadaveric dissections or prosections.

Long-Term Improvement of Chronic Low-Grade Inflammation After Bariatric Surgery.

PURPOSE: Bariatric surgery (BS) was shown to improve inflammatory markers in previous short-term follow-up studies. The aim of the present study was to assess the long-term effects of BS on chronic low-grade inflammation markers related to severe obesity. Moreover, the meaning of the type of BS procedure as well as the remission of type 2 diabetes (T2D) for inflammatory status up to 4 years after BS was analyzed. MATERIALS AND METHODS: In a retrospective cohort study including 163 patients at baseline, inflammatory and metabolic parameters were assessed at 4 time points: before surgery (baseline), 6 months after surgery (visit 1), 2 years after surgery (visit 2), and 4 years after surgery (visit 3). Univariate regression analysis was used to identify variables that were thought to determine change in inflammatory parameters. RESULTS: CRP, hs-CRP, leucocytes, and ferritin significantly declined in the mid- and long-term according to the U-shaped curve of weight loss (p<0.001). Change in body mass index (BMI) at long-time follow-up showed a significant linear effect on change in leucocytes (B=0.082; p<0.001) and change in hs-CRP (B=0.03; p<0.05). There was a strong, positive correlation between T2D and hs-CRP at visit 2 (rs=0.195; p<0.05) and visit 3 (rs=0.36; p=0.001). With regard to type of surgery and gender, there were no significant differences in inflammatory parameters. CONCLUSION: BS is able to reduce obesity-related chronic low-grade inflammation up to 4 years after surgical intervention. The improvement in metaflammation is related to the change in BMI and remission of T2D in the long-term.