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.

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.

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.

Body donation as a grateful gift for a long and active life with a Björk-Shiley valve.

An 87-year-old patient donated his body to the Institute of Anatomy and Cell Biology in gratefulness for the longevity of a Björk-Shiley convexo-concave (BSCC) prosthetic aortic valve, implanted 34 years ago. The dissection of the enlarged heart showed no major signs of thrombosis, malignant fibrosis, or any other relevant issue that could potentially lead to valve failure as in other patients. Despite the reported high mortality rate of the earlier designs, especially of the BSCC valves, some patients survived for longer than expected. In more than 34 years after the BSCC valve implantation, the patient was a very active and lively man, working both as full-time and volunteer firefighter. The lifespan of this BSCC valve is among the longest reported.

Anatomical study of Lapidus arthrodesis using two different plantar plate systems.

BACKGROUND: First tarsometatarsal arthrodesis (modified Lapidus procedure) constitutes a sufficient treatment for moderate to severe hallux valgus deformity and first ray instability. The plantar plate arthrodesis was shown to provide superior mechanical stability and less postoperative complications than screw fixation or dorsal plating. Nevertheless, the in-brought hardware may cause irritation of the tibialis anterior or peroneus longus tendon requiring explantation of the material in some cases. The purpose of this study was to investigate the potential of tendon irritation after plantar first tarsometatarsal joint arthrodesis in a cadaver study. METHODS: Plantar plate arthrodesis was performed as in real surgery on twelve pairs of fresh frozen cadaveric feet. Two different plate systems were randomly allocated to each pair of feet. After plate fixation careful dissection of the feet followed to analyze potential tendon irritation and to determine a "safe zone" for plantar plate placement. RESULTS: A "safe zone" between the insertion sties of tibialis anterior and peroneus longus tendon was found and proven to be sufficiently exposed using a standard medio-plantar approach. Both plates were fixed in this zone without compromising central tendon parts. Peripheral tendon parts were irritated in 42% using Darco Plantar Lapidus Plating System® (Wright Medical, Memphis, TN) and in 8% using the Plantar Lapidus Plate® (Arthrex, Naples, FL). Bending of the anatomically preshaped plates is often necessary to ensure optimal fit on the bone surface. CONCLUSIONS: Modified Lapidus procedure with plantar plating of the first tarsometatarsal joint can be performed safely without compromising central tendon parts via standard medio-plantar approach. LEVEL OF CLINICAL EVIDENCE: 5, Cadaver Study.

A comparative study of bone biopsies from the iliac crest, the tibial bone, and the lumbar spine.

BACKGROUND: Patients with an impaired renal function show a high incidence of bone and mineral disturbances. These 'chronic kidney disease - mineral and bone disorders' (CKD-MBD) range from high turnover osteoporosis to adynamic bone disease. Currently, the histomorphometric analysis of a bone biopsy taken from the iliac crest is viewed as the gold standard for CKD-MBD subtype differentiation. However, the clinical relevance of such a biopsy is questionable since iliac crest fractures are an extremely rare finding. Therefore, we aimed to elucidate if the histomorphometric parameter 'trabecular bone volume (BV/TV)' from the iliac crest is representative for other biopsy locations. We chose two skeletal sites of higher fracture risk for testing, namely, the tibial bone and the lumbar spine, to examine if the current gold standard of bone biopsy is indeed golden. METHODS: Bone biopsies were taken from 12 embalmed body donors at the iliac crest, the proximal tibia, and the lumbar vertebral body, respectively. Masson-Goldner stained sections of methyl methacrylate embedded biopsies were used for trabecular bone volume calculation. Furthermore, exemplary µ-computed tomography (XtremeCT) scans with subsequent analysis were performed. RESULTS: Median values of trabecular bone volume were comparable between all body donors with median (interquartile range, IQR) 18.3% (10.9-22.9%) at the iliac crest, 21.5% (9.5-40.1%) at the proximal tibia, and 16.3% (11.4-25.0%) at the lumbar spine. However, single values showed extensive intra-individual variation, which were also confirmed by XtremeCT imaging. CONCLUSIONS: Distinct intra-individual heterogeneity of trabecular bone volume elucidate why a bone biopsy from one site does not necessarily predict patient relevant endpoints like hip or spine fractures. Physicians interpreting bone biopsy results should know this limitation of the current gold standard for CKD-MBD diagnostic, especially, when systemic therapeutic decisions should be based on it.

The long-term effects of adolescent pregnancies in a community in Northern Ghana on subsequent pregnancies and births of the young mothers.

BACKGROUND: In Ghana, adolescents represent 22% of the total population. The rates of adolescent pregnancies are high. Of all births registered in the country in 2014, 30% were by adolescents, and 14% of adolescents aged between 15 and 19 years had begun childbearing. Pregnancies and deliveries of adolescents are accompanied by more risks as compared to older women. The aim of the study was to explore the long-term effects of adolescent pregnancies on subsequent pregnancies and births and on the socioeconomic status of the women. METHOD: A cross-sectional interviewer-performed survey of a purposive sample of 400 women in one community of Northern Ghana was conducted. Relationships between the age at first pregnancy and complications such as cesarean section, preterm or stillbirth and others were explored in 143 patients using the statistical program SPSS (Statistical Package for the Social Sciences). RESULT: Results show that adolescent women (<19 years at their first pregnancy) have an 80% higher risk for a cesarean section for the first and subsequent births as compared to older women (≥ 19 years). Furthermore, younger mothers have a 45% higher risk of stillbirths and a 30% increased risk of losing their baby within the first 6 weeks after birth. There was no difference in the socioeconomic status between the two age groups. CONCLUSION: Adolescent pregnancies are risk factors for the outcome of subsequent pregnancies of these mothers. This study, for the first time, shows that not only the first pregnancy and birth of very young women are negatively influenced by the early pregnancy but also subsequent pregnancies and births. While this study is of a purposive sample of women in one community, the clinical relevance of this study should not only be interesting for healthcare practitioners in Northern Ghana and other African regions but also for prevention campaigns in these regions.

Effect of a single dialysis session on cognitive function in CKD5D patients: a prospective clinical study.

BACKGROUND: Cognitive function declines in parallel to the decrease in glomerular filtration rate, best epitomized by the markedly reduced cerebral performance in patients undergoing maintenance haemodialysis [chronic kidney disease stage 5 dialysis (CKD5D)]. Aside from structural permanent damage, there seems to be a reversible part of low cognitive performance. The potential effect of a single dialysis session on cognitive function remains still elusive. The aim of the study was to assess cognitive function using a widespread test battery and avoiding excluding effects of circadian variations. METHODS: Twenty-eight medically stable CKD5D patients (age: 54.9 ± 13.2 years, dialysis vintage: 46.2 ± 51.0 month) at two tertiary care centres with outpatient dialysis units were enrolled. Cognitive testing was always performed twice within 24 h, 1 h prior to haemodialysis (T1pre-dialysis) as well as 19 h after the end of dialysis (T2post-dialysis) including assessment of memory, attention and concentration, executive functioning, word fluency and psychomotor speed by using a well-validated neuropsychological test battery. Patients were randomized into two groups. One group was examined before (T1pre-dialysis) and after (T2post-dialysis) Dialysis Session 1. The other group was first examined the day after Dialysis Session 1 (T2post-dialysis) and then before Dialysis Session 2 (T1pre-dialysis) in order to exclude potential learning effects. Twenty age-matched subjects with normal excretory renal function were used for comparison. RESULTS: Neuropsychological testing found that the CKD5D performed significantly worse on measures of alertness, attention, working memory, logical and visual memory, word fluency and executive functions compared with non-CKD subjects. No differences in short-term memory, selective attention, as well as problem-solving and planning were found between CKD5D patients and non-CKD subjects. A single haemodialysis session led to a significant improvement in logical (Rivermead Behaviour Memory Test story: P < 0.001) and visual memories [Rey-Osterrieth Complex Figure Test (RCFT) memory quotient: P < 0.001], psychomotor speed [Trail Making Test (TMT) B: P = 0.020], activity planning (executive functions) (RCFT copy/points deduction: P < 0.001) and concentration (TMT A: P < 0.001). CONCLUSION: Our data demonstrate improvements in memory functions, executive functions and psychomotor abilities after a single dialysis session, pointing to a reversible component of low cognitive performance in CKD5D.

Role of the endogenous nitric oxide inhibitor asymmetric dimethylarginine (ADMA) and brain-derived neurotrophic factor (BDNF) in depression and behavioural changes: clinical and preclinical data in chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) exhibit a high prevalence of neuropsychiatric alterations, including depression and behavioural changes. CKD is also associated with decreased physical activity not fully explained by co-morbidities. In patients without CKD, the brain-derived neurotropic factor (BDNF) as well as the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) had been suspected to be involved in major depression. The aim of our study was to examine the role of ADMA and BDNF in the behaviour of haemodialysis patients (CKD5D) as well as in a rat model of 5/6 nephrectomy and chronic ADMA infusion alone. METHODS: Eleven (5F/6M) CKD5D patients underwent Beck Depression Inventory (BDI) testing along with analysis of ADMA and BDNF. Male Sprague-Dawley rats were randomly assigned to four groups: (i) saline infusion; (ii) ADMA (250 µg/kg/day) infusion via osmotic mini pumps; (iii) 5/6 nephrectomy; (iv) untreated controls. After 28 days, the animals underwent behavioural tests measuring anxiety, locomotion and investigative behaviour. Animals were sacrificed, blood samples were drawn and analysed and hippocampal immunohistology for BDNF was performed. RESULTS: In CKD5D patients, decreased BDNF levels correlated with higher scores of depression (Pearson r = -0.8156, P = 0.002). ADMA infusion led to a significant decrease of BDNF while the decrease of BDNF in 5/6 nephrectomy was not significant. However, an attenuated hippocampal BDNF expression could be detected in 5/6 nephrecomized animals. Decreased spontaneous locomotor activity was shown in ADMA-infused rats [15.9 (13.5-26.1) lines crossed/min] and 5/6 nephrectomy [14.6 (6.1-20.2) lines crossed/min] when compared with controls [32.5 (15.3-42.4) lines crossed/min]. Anxiety-like behaviour tested by hole investigation time was significantly more pronounced in 5/6 nephrectomy [24 (6-44) s] when compared with ADMA infusion [64 (28-93) s] and controls [33 (26-65) s]. CONCLUSIONS: Progressive renal failure in rats is accompanied by a marked increase of ADMA and a decrease in BDNF. 5/6 nephrectomy leads to significantly decreased exploratory behaviour and locomotion. Both behaviours could be reproduced by ADMA infusion alone. Indicators of anxiety were more pronounced in ADMA-infused animals when compared with 5/6 nephrectomized rats. Furthermore, an inverse relationship of BDNF and BDI in 11 CKD5D patients was shown.

Cement augmented anterior odontoid screw fixation is biomechanically advantageous in osteoporotic patients with Anderson Type II fractures.

STUDY DESIGN: A biomechanical human cadaveric study. OBJECTIVE: The authors tested a cannulated and perforated lag screw and compared in situ polymethylmethacrylate (PMMA) augmentation against nonaugmentation for fixation of osteoporotic type II odontoid fractures. SUMMARY OF BACKGROUND DATA: Osteoporosis has been identified as a strong predictor for pseudarthrosis after screw fixation of type II odontoid fractures with cut-out through the anterior wall of C2 as the most frequent mode of implant failure. The concept of PMMA augmentation of the proximal screw shank could serve as a useful supplement in this context. METHODS: A total of 18 fresh-frozen human cadaveric C2 vertebrae were harvested (median 86.5 y; range, 69-98 y). Reduced bone quality was verified by quantitative computed tomography. Type II odontoid fractures were created and repaired with a cannulated lag screw, which has perforations in the proximal screw shank. Additional PMMA augmentation was carried out for 9 specimens. The position of the screw and cement distribution were evaluated by computed tomography. Values for maximum force to failure, energy to failure, and stiffness were statistically compared between cement augmented and nonaugmented screws. RESULTS: Cement distribution in the C2 vertebral body was circumferential around the screw shank without leakage into the spinal canal or into the fracture gap in all 9 specimens. The cement augmented screws showed a 2.4 times higher maximum force to failure (363±94 N, P<0.001), a 2.7 times higher energy to failure (1300±698 mJ, P<0.001), and a 1.76 times higher stiffness (90±35 N/mm, P=0.031) in comparison with the nonaugmented screws. CONCLUSIONS: Cement augmentation for fixation of osteoporotic type II odontoid fractures showed biomechanical advantages. It was also shown that cement augmentation of the newly developed screw is technically easy and safe under in vitro conditions. The technique might be useful with regard to the surgical treatment of elderly patients with osteoporotic odontoid fractures.

Functions of the temporomandibular system in extracranial chronic pain conditions: modulatory effects on nocifensive behavior in an animal model.

OBJECTIVE: Mastication may be able to activate endogenous pain inhibitory mechanisms and therefore lead to modulation of nociceptive processing. The purpose of this study was to examine the possible effect of food consistency on noxious input from the spinal system. METHODS: Three groups of adult male Sprague-Dawley rats were given an injection of complete Freund adjuvant in a hind paw 10 days after eating soft or hard food (one group received a saline injection-the control group [C]; the other group (D) received no injection). Nocifensive behavior was assessed with the use of the hot plate and tail flick assays at 1, 3, 6, and 12 hours and at 6.5 days after injection for groups A/B, and c-Fos activity was assessed in the brain after testing. Groups C/D had hot plate testing at 1 hour and 6.5 days. The data were analyzed by general linear modeling and 1-way analysis of variance. RESULTS: There was a small increase in the hot plate percent maximum possible effect (MPE) from -45.7 to -61.1 in group A over the length of the experiment, but a very small decrease for group B over the same period (-33.5 to -28.8). For the saline control group, there was a small increase toward 0 %MPE over the same time frame (-15.0 to 1.7). The %MPE differences were significant between groups A and C (P < .0005), but not significant between the other groups (F = 13.34, df = 2, P = .001, observed power = 99%). Using the pooled results (all time points), the differences between all groups were significant (P < .0005). There were no significant differences in the tail flick test. c-Fos was mainly observed in the raphe pallidus area with significant differences between groups A and B at 3 and 6 hours after injection of CFA (P = .027 and .022, respectively). CONCLUSIONS: The results of this study indicate that food consistency (hardness) influences nocifensive behavior in this animal model via a descending pathway operating at the supraspinal level.

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.

Effect of chronic elevated asymmetric dimethylarginine (ADMA) levels on granulopoiesis.

The endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) is elevated in both animal models of chronic inflammatory disorders as well as in patients with chronic inflammatory disease. In vivo data suggest that ADMA can increase the number of circulating monocytes and possibly affect their adhesion potential in vitro. The aim of our study was to evaluate possible effects of chronically elevated levels of ADMA on white blood cell count (WBC), leukocyte subsets, and WBC distribution pattern using a model of chronic exogenous ADMA infusion. Male Sprague-Dawley rats (n = 20, 10 weeks of age) were randomized to receive either (1) isotonic saline or (2) ADMA applied by osmotic mini pumps. After 28 days of infusion, all animals were sacrificed for blood and tissue sampling. WBC count, flow cytometry for subtype assessment, and histological assessment were performed. Over a time period of 28 days, continuous ADMA infusion significantly increased mean plasma levels (1.26 ± 0.07 µmol/l) as compared to saline infusion (0.57 ± 0.02 µmol/l). Clinical side effects were not observed. Despite a physiologically relevant rise in ADMA plasma levels, measured by decrease of the L-arginine/AMDA ratio-a surrogate parameter of NO production capacity-there was no effect on WBC count or pattern of leukocyte subsets. Numbers and morphology of peripheral blood cells as well as number of NK-cells leveling liver and spleen were not affected by chronic ADMA infusion. Chronically elevated ADMA levels in otherwise healthy rats did not affect WBC counts or leukocyte subsets. Furthermore, anemia frequently found in patients with progressive renal failure and elevated ADMA levels, was not observed. In a chronic inflammatory state, elevated ADMA levels themselves are rather the result than the cause of the underlying inflammatory process.

CD3+CD56+natural killer T cells in fibromyalgia syndrome patients: association with the intensity of depression.

OBJECTIVES: Fibromyalgia syndrome (FMS) patients have multiple symptoms, including mental symptoms such as depression. Natural killer T (NKT) cells have shown to be correlated with depression. However, up to now there is no information regarding the role of CD3+CD56+NKT cells in FMS patients, especially in the intensity of mental symptoms. The present study aimed to observe the role of CD3+CD56+NKT cells level in FMS patients in relation to the intensity of depression. METHODS: Ninety-six female patients who matched definition of FMS were divided into subgroups of depressions according to Hospital Anxiety and Depression Scale (HADS) score (HADS-Depression <8; 8-10; and >10). CD3+CD56+NKT cells from peripheral blood were measured by fluorescence-activated cell sorting methods. RESULTS: ANOVA test in the subgroup of depression of FMS patient showed significant differences. Additionally, the differences were observed in HADSD <8 and >10. The use of antidepressant significantly altered the level of CD3+CD56+NKT cells. A blocking variable ANCOVA with antidepressant as covariate showed main effects in the subgroup of depression, however, the interaction of antidepressant and the subgroup of depression did not influence the level of CD3+CD56+NKT cells. CONCLUSIONS: These results suggest that CD3+CD56+NKT cells could play a role as a mediator in mental symptom such as depression in FMS patients. It seems the role of antidepressant in the mood intensity is not mediated by CD3+CD56+NKT cells in FMS patients. Additionally, subgrouping FMS patients based on the intensity of mental symptoms may help to optimise the treatments.

Enzymes of urea synthesis are expressed at the ocular surface, and decreased urea in the tear fluid is associated with dry-eye syndrome.

PURPOSE: The present study aims at determining whether enzymes of urea synthesis are expressed in the human lacrimal gland and in tissues of ocular surface (conjunctiva, cornea), to give evidence for the hypothesis that urea can be locally formed from ocular tissues and is important for the composition of the tear fluid. METHODS: The presences of enzymes (arginase 1, 2 and agmatinase) that directly contribute to the formation of urea were investigated in the lacrimal gland and tissues of ocular surface by RT-PCR and immunohistochemistry. We collected tear fluid, aqueous humour, and blood samples from a total of 38 subjects, and tear fluid samples from a total of 78 subjects, with and without dry-eye syndrome (DES, keratoconjunctivitis sicca), and determined the urea concentration. RESULTS: The enzymes arginase 1, 2 and agmatinase were expressed in all tissues examined except for arginase 1, which was not expressed in the cornea. There was no correlation of urea concentration in tear fluid with aqueous humour and blood plasma (r = 0.13, p = 0.58 and r = 0.45, p = 0.05 respectively). However, correlation of urea concentration between aqueous humour and blood plasma was highly significant (r = 0.7, p = 0.0001). The concentration of urea in the tear fluid of patients with DES compared to healthy control group was significantly reduced (p < 0.0001). CONCLUSION: Enzymes that are directly involved in the formation of urea are expressed in ocular tissues. This may imply that in the ocular surface is a well-coordinated system of enzymes that can produce urea which might be independent of external urea supply.

Imaging in anatomy: a comparison of imaging techniques in embalmed human cadavers.

BACKGROUND: A large variety of imaging techniques is an integral part of modern medicine. Introducing radiological imaging techniques into the dissection course serves as a basis for improved learning of anatomy and multidisciplinary learning in pre-clinical medical education. METHODS: Four different imaging techniques (ultrasound, radiography, computed tomography, and magnetic resonance imaging) were performed in embalmed human body donors to analyse possibilities and limitations of the respective techniques in this peculiar setting. RESULTS: The quality of ultrasound and radiography images was poor, images of computed tomography and magnetic resonance imaging were of good quality. CONCLUSION: Computed tomography and magnetic resonance imaging have a superior image quality in comparison to ultrasound and radiography and offer suitable methods for imaging embalmed human cadavers as a valuable addition to the dissection course.

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.

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.

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.