The effect of increased fruit and vegetable consumption on blood pressure and lipids: a pooled analysis of six randomised controlled fruit and vegetable intervention trials.

BACKGROUND: Increasing fruit and vegetable (FV) consumption is associated with reduced cardiovascular disease risk in observational studies but with little evidence from randomised controlled trials (RCTs). The impact of concurrent pharmacological therapy is unknown. OBJECTIVE: To pool data from six RCTs to examine the effect of increasing FV intake on blood pressure (BP) and lipid profile, also exploring whether effects differed by medication use. DESIGN: Across trials, dietary intake was assessed by diet diaries or histories, lipids by routine biochemical methods and BP by automated monitors. Linear regression provided an estimate of the change in lipid profile or BP associated with a one portion increase in self-reported daily FV intake, with interaction terms fitted for medication use. RESULTS: The pooled sample included a total of 554 participants (308 males and 246 females). Meta-analysis of regression coefficients revealed no significant change in either systolic or diastolic BP per portion FV increase, although there was significant heterogeneity across trials for systolic BP (I2 = 73%). Neither adjusting for change in body mass index, nor analysis according to use of anti-hypertensive medication altered the relationship. There was no significant change in lipid profile per portion FV increase, although there was a significant reduction in total cholesterol among those not on lipid-lowering therapy (P < 0.05 after Bonferroni correction). CONCLUSION: Pooled analysis of six individual FV trials showed no impact of increasing intake on BP or lipids, but there was a total cholesterol-lowering effect in those not on lipid-lowering therapy.

Characterizing Diffusion from Microdialysis Catheters in the Human Brain: A Magnetic Resonance Imaging Study With Gadobutrol.

Cerebral microdialysis (CMD) catheters allow continuous monitoring of patients' cerebral metabolism in severe traumatic brain injury (TBI). The catheters consist of a terminal semi-permeable membrane that is inserted into the brain's interstitium to allow perfusion fluid to equalize with the surrounding cerebral extracellular environment before being recovered through a central non-porous channel. However, it is unclear how far recovered fluid and suspended metabolites have diffused from within the brain, and therefore what volume or region of brain tissue the analyses of metabolism represent. We assessed diffusion of the small magnetic resonance (MR)-detectible molecule gadobutrol from microdialysis catheters in six subjects (complete data five subjects, incomplete data one subject) who had sustained a severe TBI. Diffusion pattern and distance in cerebral white matter were assessed using T1 (time for MR spin-lattice relaxation) maps at 1 mm isotropic resolution in a 3 Tesla MR scanner. Gadobutrol at 10 mmol/L diffused from cerebral microdialysis catheters in a uniform spheroidal (ellipsoid of revolution) pattern around the catheters' semipermeable membranes, and across gray matter-white matter boundaries. Evidence of gadobutrol diffusion was found up to a mean of 13.4 ± 0.5 mm (mean ± standard deviation [SD]) from catheters, but with a steep concentration drop off so that ≤50% of maximum concentration was achieved at ∼4 mm, and ≤10% of maximum was found beyond ∼7 mm from the catheters. There was little variation between subjects. The relaxivity of gadobutrol in human cerebral white matter was estimated to be 1.61 ± 0.38 L.mmol-1sec-1 (mean ± SD); assuming gadobutrol remained extracellular thereby occupying 20% of total tissue volume (interstitium), and concentration equilibrium with perfusion fluid was achieved immediately adjacent to catheters after 24 h of perfusion. No statistically significant change was found in the concentration of the extracellular metabolites glucose, lactate, pyruvate, nor the lactate/pyruvate ratio during gadobutrol perfusion when compared with period of baseline microdialysis perfusion. Cerebral microdialysis allows continuous monitoring of regional cerebral metabolism-the volume of which is now clearer from this study. It also has the potential to deliver small molecule therapies to focal pathologies of the human brain. This study provides a platform for future development of new catheters optimally designed to treat such conditions.

Mental health is strongly associated with capability after lower extremity injury treated with free flap limb salvage or amputation.

BACKGROUND: Knowledge about factors associated with long-term outcomes, after severe traumatic injury to the lower extremity, can aid with the difficult decision whether to salvage or amputate the leg and improve outcome. We therefore studied factors independently associated with capability at a minimum of 1 year after amputation or free flap limb salvage. METHODS: We included 135 subjects with a free flap lower extremity reconstruction and 41 subjects with amputation, between 1991 and 2021 at two urban-level 1 trauma centers with a mean follow-up of 11 ± 7 years. Long-term physical functioning was assessed using the Physical Component Score (PCS) of the Short-Form 36 (SF36) and the Lower Extremity Functional Scale (LEFS) questionnaires. Independent variables included demographics, injury characteristics, and the Mental Component Score (MCS) of the SF36. RESULTS: Greater mental health was independently and strongly associated with greater capability, independent of amputation or limb reconstruction. Mental health explained 33% of the variation in PCS and 57% of the variation in LEFS. Injury location at the knee or leg was associated with greater capability, compared to the foot or ankle. Amputation or limb reconstruction was not associated with capability. DISCUSSION: This study adds to the growing body of knowledge that physical health is best regarded through the lens of the bio-psycho-social model in which mental health is a strong determinant. This study supports making mental health an important aspect of rehabilitation after major lower extremity injury, regardless of amputation or limb salvage.

Inferring country-specific import risk of diseases from the world air transportation network.

Disease propagation between countries strongly depends on their effective distance, a measure derived from the world air transportation network (WAN). It reduces the complex spreading patterns of a pandemic to a wave-like propagation from the outbreak country, establishing a linear relationship to the arrival time of the unmitigated spread of a disease. However, in the early stages of an outbreak, what concerns decision-makers in countries is understanding the relative risk of active cases arriving in their country-essentially, the likelihood that an active case boarding an airplane at the outbreak location will reach them. While there are data-fitted models available to estimate these risks, accurate mechanistic, parameter-free models are still lacking. Therefore, we introduce the 'import risk' model in this study, which defines import probabilities using the effective-distance framework. The model assumes that airline passengers are distributed along the shortest path tree that starts at the outbreak's origin. In combination with a random walk, we account for all possible paths, thus inferring predominant connecting flights. Our model outperforms other mobility models, such as the radiation and gravity model with varying distance types, and it improves further if additional geographic information is included. The import risk model's precision increases for countries with stronger connections within the WAN, and it reveals a geographic distance dependence that implies a pull- rather than a push-dynamic in the distribution process.

Predictors of postoperative lumpectomy size in breast-conserving surgery in breast cancer patients: a retrospective cohort study.

BACKGROUND: Oncoplastic reconstructive surgery as an extension of breast-conserving surgery leads to better aesthetic results, an increase in tumor-free margins, and a reduction of re-excision rates. However, oncologic resection is often more extensive than expected, sometimes resulting in the plastic surgeon deviating from the predetermined plan. For optimal planning of the reconstruction, it is mandatory to estimate volume defects after lumpectomy as accurately as possible. This study aims to find preoperative predictors of lumpectomy resection size. METHODS: All consecutive patients diagnosed with invasive breast carcinoma or carcinoma in situ and treated primarily with breast-conserving surgery between 2018 and 2020 at the University Medical Center Utrecht and Alexander Monro Hospital were included. Variables measured were patient characteristics and tumor characteristics. Data was analyzed in a multiple linear regression analysis. RESULTS: A total of 423 cases (410 patients) were included, with a median age of 58 (range 32-84) and a mean BMI of 25.0 (SD=9.3). The mean maximum radiological tumor diameter was 18.0 mm (SD=13.2), and the mean maximum lumpectomy diameter was 58.8 mm (SD=19.2). Multiple linear regression analysis found an explained variance of R 2 = 0.60 (p = < .00), corrected for operating surgeon. Significant predictors for postoperative lumpectomy size were BMI, breast size, and maximum preoperative radiological tumor diameter. Moreover, a predictive tool for lumpectomy size was developed and a web-based application was created on www.evidencio.com under the title ''Predicted lumpectomy size'', to facilitate the use of our tool in a clinical setting. CONCLUSION: Postoperative lumpectomy size can be predicted with BMI, breast size and radiological tumor size. This model could be beneficial for (plastic) breast surgeons in planning reconstructions and to prepare and inform their patients more accurately.

TMED10 mediates the loading of neosynthesised Sonic Hedgehog in COPII vesicles for efficient secretion and signalling.

The morphogen Sonic Hedgehog (SHH) plays an important role in coordinating embryonic development. Short- and long-range SHH signalling occurs through a variety of membrane-associated and membrane-free forms. However, the molecular mechanisms that govern the early events of the trafficking of neosynthesised SHH in mammalian cells are still poorly understood. Here, we employed the retention using selective hooks (RUSH) system to show that newly-synthesised SHH is trafficked through the classical biosynthetic secretory pathway, using TMED10 as an endoplasmic reticulum (ER) cargo receptor for efficient ER-to-Golgi transport and Rab6 vesicles for Golgi-to-cell surface trafficking. TMED10 and SHH colocalized at ER exit sites (ERES), and TMED10 depletion significantly delays SHH loading onto ERES and subsequent exit leading to significant SHH release defects. Finally, we utilised the Drosophila wing imaginal disc model to demonstrate that the homologue of TMED10, Baiser (Bai), participates in Hedgehog (Hh) secretion and signalling in vivo. In conclusion, our work highlights the role of TMED10 in cargo-specific egress from the ER and sheds light on novel important partners of neosynthesised SHH secretion with potential impact on embryonic development.

Enhancing global preparedness during an ongoing pandemic from partial and noisy data.

As the coronavirus disease 2019 spread globally, emerging variants such as B.1.1.529 quickly became dominant worldwide. Sustained community transmission favors the proliferation of mutated sub-lineages with pandemic potential, due to cross-national mobility flows, which are responsible for consecutive cases surge worldwide. We show that, in the early stages of an emerging variant, integrating data from national genomic surveillance and global human mobility with large-scale epidemic modeling allows to quantify its pandemic potential, providing quantifiable indicators for pro-active policy interventions. We validate our framework on worldwide spreading variants and gain insights about the pandemic potential of BA.5, BA.2.75, and other sub- and lineages. We combine the different sources of information in a simple estimate of the pandemic delay and show that only in combination, the pandemic potentials of the lineages are correctly assessed relative to each other. Compared to a country-level epidemic intelligence, our scalable integrated approach, that is pandemic intelligence, permits to enhance global preparedness to contrast the pandemic of respiratory pathogens such as SARS-CoV-2.

Bulging after DIEP Breast Reconstruction: New Insights Concerning Rectus Diastasis and Medial Perforator Harvest.

The aim of this study was to evaluate the association between flap harvest technique and occurrence of abdominal bulging. Methods: A retrospective analysis of 159 patients undergoing DIEP flap breast reconstruction between 2014 and 2021 in the University Medical Center Utrecht was conducted. Outcomes measured were preoperative rectus diastasis, flap weight, laterality of flap harvest (unilateral or bilateral), timing of the harvest (immediate or delayed), number of perforators harvested (single or multiple), and location of the harvested perforator (medial, lateral, or both). Results: In 159 patients, 244 DIEP flaps were performed, 16 of these donor-sites (6.6%) developed a clinically evident abdominal bulge. When preoperative rectus abdominis diastasis was found (n = 97), postoperative bulging occurred significantly more often (P < 0.01). Patients in whom the medial perforator artery was harvested for reconstruction (n = 114) showed less abdominal bulging than patients in whom the lateral (n = 92) was harvested (P = 0.02). Using single versus multiple perforators for the DIEP flap, bilateral versus unilateral reconstruction or timing of the operation showed no significant difference in outcome of bulging (P = 1.00, P = 0.78, P = 0.59, respectively). Conclusions: The incidence of bulging in our study cohort is comparable to the literature. Harvesting the medial perforator artery for the DIEP flap showed less abdominal bulging than using the lateral perforator artery in a DIEP flap breast reconstruction. Also, preoperative rectus diastasis was found to be an important risk factor for the occurrence of bulging.

Germany's fourth COVID-19 wave was mainly driven by the unvaccinated.

Background: While the majority of the German population was fully vaccinated at the time (about 65%), COVID-19 incidence started growing exponentially in October 2021 with about 41% of recorded new cases aged twelve or above being symptomatic breakthrough infections, presumably also contributing to the dynamics. So far, it remained elusive how significant this contribution was and whether targeted non-pharmaceutical interventions (NPIs) may have stopped the amplification of the crisis. Methods: We develop and introduce a contribution matrix approach based on the next-generation matrix of a population-structured compartmental infectious disease model to derive contributions of respective inter- and intragroup infection pathways of unvaccinated and vaccinated subpopulations to the effective reproduction number and new infections, considering empirical data of vaccine efficacies against infection and transmission. Results: Here we show that about 61%-76% of all new infections were caused by unvaccinated individuals and only 24%-39% were caused by the vaccinated. Furthermore, 32%-51% of new infections were likely caused by unvaccinated infecting other unvaccinated. Decreasing the transmissibility of the unvaccinated by, e. g. targeted NPIs, causes a steeper decrease in the effective reproduction number R than decreasing the transmissibility of vaccinated individuals, potentially leading to temporary epidemic control. Reducing contacts between vaccinated and unvaccinated individuals serves to decrease R in a similar manner as increasing vaccine uptake. Conclusions: A minority of the German population-the unvaccinated-is assumed to have caused the majority of new infections in the fall of 2021 in Germany. Our results highlight the importance of combined measures, such as vaccination campaigns and targeted contact reductions to achieve temporary epidemic control.

Association of TGFB1 rs1800469 and BCMO1 rs6564851 with coronary heart disease and IL1B rs16944 with all-cause mortality in men from the Northern Ireland PRIME study.

BACKGROUND: Historically, high levels of morbidity and mortality have been associated with cardiovascular disease in the Northern Ireland population. Previously reported associations between single nucleotide polymorphisms (SNPs) and cardiovascular disease within other populations have not always been consistent. OBJECTIVE: To investigate associations between 33 SNPs with fatal or non-fatal incident coronary heart disease (CHD) events and all-cause mortality in the Northern Irish participants of the Prospective Epidemiological Study of Myocardial Infarction (PRIME). METHOD: Phase 2 of the PRIME study prospectively evaluated 2,010 men aged 58-74 years in Northern Ireland for more than 10 years for incident CHD events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass, and cardiac death) and more than 15 years for all-cause mortality. SNPs previously reported in association with cardiovascular outcomes were evaluated against incident CHD events and all-cause mortality using Cox's proportional hazards models adjusted for established cardiovascular disease risk factors. RESULTS: During the follow-up period, 177 incident CHD events were recorded, and 821 men died. Both BCMO1 rs6564851 (Hazard ratio [HR] = 0.76; 95% confidence intervals [CI]: 0.60-0.96; P = 0.02) and TGFB1 rs1800469 (HR = 1.30; CI: 1.02-1.65; P = 0.04) were significantly associated with incident CHD events in adjusted models. Only IL1B rs16944 was significantly associated with all-cause mortality (HR = 1.18; CI: 1.05-1.33; P = 0.005). No associations remained significant following Bonferonni correction for multiple testing. CONCLUSION: We report a novel association between BCMO1 rs6564851 and risk of incident CHD events. In addition, TGFB1 rs1800469 and IL1B rs16944 were associated with the risk of incident CHD events and all-cause mortality outcomes respectively, supporting previously reported associations.