A Systematic Review of Lipid-Focused Cardiovascular Disease Research: Trends and Opportunities.

Lipids are important modifiers of protein function, particularly as parts of lipoproteins, which transport lipophilic substances and mediate cellular uptake of circulating lipids. As such, lipids are of particular interest as blood biological markers for cardiovascular disease (CVD) as well as for conditions linked to CVD such as atherosclerosis, diabetes mellitus, obesity and dietary states. Notably, lipid research is particularly well developed in the context of CVD because of the relevance and multiple causes and risk factors of CVD. The advent of methods for high-throughput screening of biological molecules has recently resulted in the generation of lipidomic profiles that allow monitoring of lipid compositions in biological samples in an untargeted manner. These and other earlier advances in biomedical research have shaped the knowledge we have about lipids in CVD. To evaluate the knowledge acquired on the multiple biological functions of lipids in CVD and the trends in their research, we collected a dataset of references from the PubMed database of biomedical literature focused on plasma lipids and CVD in human and mouse. Using annotations from these records, we were able to categorize significant associations between lipids and particular types of research approaches, distinguish non-biological lipids used as markers, identify differential research between human and mouse models, and detect the increasingly mechanistic nature of the results in this field. Using known associations between lipids and proteins that metabolize or transport them, we constructed a comprehensive lipid-protein network, which we used to highlight proteins strongly connected to lipids found in the CVD-lipid literature. Our approach points to a series of proteins for which lipid-focused research would bring insights into CVD, including Prostaglandin G/H synthase 2 (PTGS2, a.k.a. COX2) and Acylglycerol kinase (AGK). In this review, we summarize our findings, putting them in a historical perspective of the evolution of lipid research in CVD.

Effects of particle size reduction of meadow hay on feed intake, performance, and apparent total tract nutrient digestibility in dairy cows.

Forage-based diets are encouraged in organic dairy cattle production as this can increase the net human food supply, but their voluminous nature can limit dry matter intake (DMI) and performance. This study investigates the effects of a substantial particle size reduction of hay on dairy cows' feed intake, performance, and body characteristics, as well as on apparent total tract digestibility (ATTD). Eighteen lactating Holstein cows were allocated to two balanced feeding groups. The control group received long stem hay with a conventional particle size (CON), the experimental group received chopped hay (RED). Both groups were supplemented with concentrates (3.6 kg/d, DM basis). After 14 adaptation days, data were collected for 20 consecutive days. A covariate period of 21 days preceded the experimental feeding period. Particles retained on the 19-, 8- and 4-mm screens and on the pan of the Penn State Particle Separator accounted for 21%, 20%, 20% and 39% of the RED hay. CON hay consisted of 72% large particles, followed by 8%, 7% and 13% retained on the other screens. Average DMI levels of cows in the CON group reached 20.8 kg/d, with a nonsignificant increase (+1.05 kg/d) in the RED group (p = 0.28). Intakes of both NFC (+0.65 kg/d, p = 0.01) and CP (+0.28 kg/d, p = 0.05) were significantly greater in the RED group, resulting in a slightly increased milk yield (+0.8 kg energy corrected milk/d) (p = 0.45), likely because the ATTD decreased significantly when feeding RED hay. No impact was observed on energy balance (103.7 vs 103.9%, p = 0.95), feed conversion efficiency (kg ECM/kg DMI), or N use efficiency. Overall, the results indicate increases in intake of NFC and CP in the RED group when feeding a hay-based (>83%, DM basis) diet, but also a decrease in nutrient digestibility, likely due to increased passage rate, potentially because of the high fraction of hay particles < 4 mm. In conclusion, hay-based rations with a lower proportion of fine particles should be tested to exploit the potential of particle size reduction in terms of improving hay use efficiency.

[Ventral Hernia Repair in Endoscopically Total Extrapertoneal Technique (eTEP) - Evaluation of Postoperative Outcome and One Year Follow-up]. / Ventralhernienversorgung in endoskopischer total extraperitonealer Technik (eTEP) ­ Evaluation der postoperativen Ergebnisse und des 1-Jahres-Follow-ups.

BACKGROUND: Several recent meta-analyses have identified the retromuscular plane as the preferred mesh position in ventral hernia repair. Open surgery used to be the standard technique for these procedures. However, new minimally invasive techniques with totally extraperitoneal access and mesh positioning in the retromuscular plane have evolved. METHODS: Between September 2018 and March 2019, 18 consecutive patients with ventral hernia were treated endoscopically in the totally extraperitoneal technique. Depending on the localisation and size of the hernia, the appropriate access was chosen and an uncoated mesh was placed in the retromuscular space in all patients. Data of patients' characteristics as well as peri- and postoperative parameters were collected. One year after surgery, patients were asked about recurrence, pain and complications, using the questionnaire of the herniamed data base. RESULTS: No intraoperative complications were noted. Postoperatively, there was one retromuscular seroma that did not need treatment, one temporary paralysis of the radial nerve and one pulmonary embolism. None of these complications led to persistent problems. 17 of 18 patients were available for follow-up. One year follow-up showed no hernia recurrence. One patient had pain at rest requiring treatment. CONCLUSIONS: Totally extraperitoneal endoscopic hernia surgery is a safe and promising new technique that is also feasible in complex hernias and with satisfactory 1 year results. This technique can combine the advantages of minimally invasive surgery with those of extraperitoneal mesh placement.

Impact of lithium alone and in combination with antidepressants on cytokine production in vitro.

Lithium is an important psychopharmacological agent for the treatment of unipolar as well as bipolar affective disorders. Lithium has a number of side effects such as hypothyroidism and aggravation of psoriasis. On the other hand, lithium has pro-inflammatory effects, which appear beneficial in some disorders associated with immunological deficits, such as human immunodeficiency virus (HIV) infection and systemic lupus erythematosus (SLE). Therefore, immunological characteristics of lithium may be an important consideration in individualized therapeutic decisions. We measured the levels of the cytokines interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-22, IL-17 and tumour necrosis factor (TNF)-α in the stimulated blood of thirty healthy subjects supplemented with lithium alone, the antidepressants citalopram, escitalopram or mirtazapine alone, the combination of each antidepressant with lithium, and a no drug control. These drugs were tested under three blood stimulant conditions: murine anti-human CD3 monoclonal antibody OKT3 and the 5C3 monoclonal antibody (OKT3/5C3), phytohemagglutinin (PHA), and unstimulated blood. Lithium, alone and in combination with any of the tested antidepressants, led to a consistent increase of IL-1ß, IL-6 and TNF-α levels in the unstimulated as well as the stimulated blood. In the OKT3/5C3- and PHA-stimulated blood, IL-17 production was significantly enhanced by lithium. Lithium additionally increased IL-2 concentrations significantly in PHA-stimulated blood. The data support the view that lithium has pro-inflammatory properties. These immunological characteristics may contribute to side effects of lithium, but may also explain its beneficial effects in patients suffering from HIV infection or SLE.

The Influence of Airway Tree Geometry and Ventilation Frequency on Airflow Distribution.

The human lung is known to be asymmetric and heterogeneous which leads to an inhomogeneous distribution of air. Within the scope of this paper the influence of the upper airway tree geometry on ventilation distribution and the differences between conventional mechanical ventilation (CMV) and high frequency oscillatory ventilation (HFOV) will be analyzed. The comparison is carried out under the assumption of positive pressure ventilation. Thereby, the mechanics of lung tissue is expected to play a minor role. Oscillatory flow is therefore generated numerically at a 3D model geometry of the upper human airways. For large enough frequencies in the range of HFOV (here 7 Hz) the shape of the velocity profiles changes, but this had no measurable influence on the flow distribution. The flow division is rather governed by airway tree geometry, i.e., branch length, curvature, and tortuosity. A convective net transport of fresh air to the distal branches occurs due to the relocation of mass during ins-/expiration driven by secondary flow. However, a mixing by secondary flow plays a minor role as was suggested by the visualization of particle pathlines. The phenomenon of steady streaming is further investigated by calculating the mean flow of one breathing cycle. Streaming was found to contribute only to a minor percentage to the overall mass transport in the upper lung airways.

Comprehensive curriculum for phantom-based training of ultrasound-guided intercostal nerve and stellate ganglion blocks.

OBJECTIVE: Ultrasound (US)-guided pain procedures become increasingly important due to their numerous advantages. Solid proficiency is necessary, however, to minimize complications and guarantee adequate performance. To enable beginners to learn the relevant skills in the technique of US-guided stellate ganglion (SGB) and intercostal nerve block (ICB), a training curriculum was developed and tested using self-made phantoms. DESIGN: The curriculum comprised an introduction to the didactics of US, SGB, and ICB, a demonstration of the techniques by an expert user, as well as hands-on training of needle guidance using a gel pad and two phantoms. SUBJECTS: Three groups of participants with different levels of expertise with US-guided procedures took part in the curriculum: 12 medical students with no prior experience, 12 anesthesiologists with some experience, and five senior anesthesiologists who already applied these techniques on a regular basis. METHODS: Participants evaluated the curriculum via questionnaire, and their performance of time until adequate puncture, attempts required for adequate puncture, number of corrections, and unintentional punctures was assessed. RESULTS: The medical students significantly increased their speed during both nerve blocks and reduced the number of attempts and corrections necessary to perform adequate ICB. The anesthesiologists with some experience also increased their speed in both blocks. The participants rated the curriculum as good to very good. CONCLUSIONS: The combination of theoretical teaching, expert demonstration, and hands-on training on phantoms proved useful in acquiring skills needed for US-guided procedures such as SGB and ICB, and can potentially improve graduate and post-graduate medical education.

The impact of social isolation on immunological parameters in rats.

In various toxicological studies, single housing of rodents is preferred to standardize for regulatory purposes. However, housing conditions can have severe, often underestimated, impact on results in toxicological examinations. As different husbandry conditions have been shown to impose stress, we investigated their influence on plasma cytokines. Adult male Wistar rats were assigned to one group housed in cages of four and another housed singly for 28 days. Eight animals per group were tested in the forced swim test (FST) for symptoms of "behavioral despair," and in another eight animals per group, plasma concentrations of the stress hormone ACTH, of the pro-inflammatory cytokines TNF-α, IFN-γ, IL-2 and IL-22, and of the anti-inflammatory cytokines IL-4 and IL-10 were analyzed. Group-housed animals had significantly lower body weight than individually housed animals. The FST revealed symptoms of "behavioral despair" of individually housed rats accompanied by higher levels of ACTH and TNF-α but also of IL-4 and IL-10. No significant differences between housing conditions were found for IFN-γ, IL-2 and IL-22. Social isolation by husbandry conditions, apart from any other manipulation, alters the behavioral and immunological status of rats and must be considered when immunological effects are examined in various experimental protocols.

Validity of the MAGIC study: sufficient for recommendations?

According to the recommendations of the German S3 guideline, perioperative chemotherapy is an integral part of the treatment concept for advanced gastric cancer. The leading trial which examined the effects of perioperative chemotherapy is the MAGIC study. An examination of the validity of this study with a standardized method revealed shortcomings in the six areas: design, protocol, selection of patients, randomization / homogeneity of patient groups, quality of the surgical care and the statistical evaluation. These shortcomings and their influence on the study results are described in this paper to reveal the importance of these effects for discussion in guidelines committees.

Analysis of the CONKO-001 trial: Is the validity of the study sufficient to recommend adjuvant chemotherapy for pancreatic cancer?

BACKGROUND: Since randomized controlled trials have indicated that adjuvant chemotherapy prolongs survival and reduces recurrence rates after surgical resection of pancreatic adenocarcinoma, a gemcitabine based chemotherapy has become part of the interdisciplinary treatment concept for pancreatic cancer in accordance to current guidelines. OBJECTIVES: The aim of this project was to analyse the validity of the CONKO-001 trial as a basis for the recommendation of adjuvant chemotherapy in many international guidelines. METHODS: We analysed the validity of the CONKO-001 trial regarding study design, recruitment period, participating institutions, patient selection, randomisation, stratification, standardization of surgical treatment and histological examination, statistical methods and interpretation of results. We additionally analysed the study regarding the risk of bias using the RoB 2 Tool. Finally we reviewed the influence of the pharmaceutical industry and potential conflicts of interest. RESULTS: We identified several shortcomings of the study concerning the study protocol, the participating clinics, the patient recruitment, the randomization pattern, the standardization of surgical treatment and histological examination, the statistical methods, the evaluation of the results and the influence of the pharmaceutical industry. According to the Cochrane RoB 2 Tool the study was judged to raise some concerns in three of the five risk domains for the outcome "overall survival". CONCLUSIONS: Based on our review, the results of the CONKO-001-study should be revisited and critically reviewed. The recommendation to include adjuvant chemotherapy with gemcitabine deserves a critical appraisal.

Adjuvant gemcitabine after resection of pancreatic cancer without significant difference in overall survival: a retrospective cohort study.

International guidelines recommend adjuvant chemotherapy after resection of pancreatic adenocarcinoma. The administration of gemcitabine has become part of the interdisciplinary treatment concept. The authors aim to prove whether the benefit in overall survival (OS) reported in randomized controlled trials (RCTs) could be reached also for patients treated in their department. Materials and methods: The authors retrospectively analyzed the OS of all patients who underwent pancreatic resection at their clinic because of ductal adenocarcinoma between January 2013 and December 2020 in dependence on adjuvant treatment with gemcitabine. Results: Overall 133 pancreatic resections were performed between 2013 and 2020 due to malignant pancreatic pathology. Seventy-four patients had ductal adenocarcinoma. Forty patients received adjuvant gemcitabine chemotherapy postoperatively, 18 patients underwent only surgical resection, and 16 patients received other chemotherapy regimens. The authors compared the group receiving adjuvant gemcitabine (n=40) with the group undergoing surgery alone (n=18). The median age was 74 years (range: 45-85), and the median OS was 16.5 months [95% confidence interval (CI) 13-27]. Follow-up time was at least 23 months (range 23-99). No statistically significant difference in median OS was observed in the group who received adjuvant chemotherapy compared to the operation-only group [17.5 months (range: 5-99, 95% CI 14-27) versus 12.5 months (range: 1-94, 95% CI 5-66), P=0.75]. Conclusion: OS with and without adjuvant chemotherapy with gemcitabine was comparable to the results of those RCTs which serve as the basis of guideline recommendations. However, the analyzed patient cohort did not profit significantly from the adjuvant treatment.

Three-dimensional flow patterns in the upper human airways.

Flow dynamics are studied for different ventilation conditions at a three-dimensional model of the human lung airways. The model is based on Horsfield and Weibel data and bifurcates down to the sixth generation. The flow is analyzed numerically and compared to experimental data received from exactly the same model. Numerical and experimental results agree well. Based on this agreement, flow behavior for conventional mechanical ventilation (CMV) as well as for high frequency oscillatory ventilation (HFOV) conditions can be analyzed. Velocity profiles as well as secondary flow structures are investigated during different phases of the unsteady flow. It is shown that the velocity profiles at peak inspiration and expiration are very similar for CMV and HFOV, probably due to too short branch lengths for the development of a frequency-dependent velocity profile. At the flow reversal times, characteristic zones of bidirectional mass flow emerge with increasing amplitude at higher frequencies. Furthermore, secondary flow structures are analyzed. This investigation reveals that the structures only depend on the local curvature and branch orientation, but are not influenced much by the nearby upper or lower branching generations.

Oxygen transport during liquid ventilation: an in vitro study.

An in vitro experiment on the dissolved oxygen transport during liquid ventilation by means of measuring global oxygen concentration fields is presented within this work. We consider the flow in an idealized four generation model of the human airways in a range of peak Reynolds numbers of [Formula: see text]-3400 and Womersley numbers of [Formula: see text]-5. Fluorescence quenching measurements were employed in order to visualize and quantify the oxygen distribution with high temporal and spatial resolution during the breathing cycle. Measurements with varying tidal volumes and oscillating frequencies reveal short living times of characteristic concentration patterns for all parameter variations. Similarities to typical velocity patterns in similar lung models persist only in early phases during each cycle. Concentration gradients are quickly homogenized by secondary motions within the lung model. A strong dependency of peak oxygen concentration on tidal volume is observed with considerably higher relative concentrations for higher tidal volumes.

Establishment of minimally invasive ventral hernia repair with extraperitoneal mesh placement in a primary care hospital using the robotic platform.

Background: The progressive availability of robotic surgical systems opens new perspectives in abdominal wall surgery due to excellent visibility and dexterity of instruments. While complex hernias until today were treated primarily through an open access, we evaluated if this promising technology is suitable for treating the entire spectrum of a hernia center, including complex hernias. Material/methods: In 2017, minimally invasive hernia surgery with extraperitoneal mesh placement was started in Kempten hospital. Since 2019, a Da Vinci X system has been available for this purpose. In order to observe the process of transition we retrospectively analyzed all patients who underwent ventral hernia repair in the department of general and visceral surgery at our hospital between January 2016 and December 2020 and were indicated for mesh implantation. Results: In 2016, the percentage of minimally invasive procedures was 37.3%. In all of these cases an intraperitoneal mesh was implanted into the abdominal cavity. Open surgery was performed in 62.7%, of which an a retromuscular mesh was implanted in 75.7%, an intraperitoneal mesh in 21.6%, and an onlay mesh in 2.7%. In 2020, minimally invasive surgery accounted for 87.5%, of which 85.7% were performed robotically and 14.3 laparoscopically. In 94.3% of these minimally invasively treated patients the mesh was implanted in extraperitoneal position (75.8% in retromuscular and 24.2% in preperitoneal position). The percentage of complex hernias increased from 20.3% to 35.0% during the same period. Conclusion: The majority of ventral hernia procedures can be performed safely using the robot in a minimally invasive technique with extraperitoneal mesh placement without leading to an increase in complications. Robotically-assisted hernia repair is a promising new technique that is also practical for complex hernias.

How Safe is Singing Under Pandemic Conditions? - CO2-Measurements as Simple Method for Risk Estimation During Choir Rehearsals.

OBJECTIVES: The SARS-CoV-2 pandemic has forced choirs to pause or at least to restrict rehearsals and concerts. Nevertheless, an uncertainty about the risks of infection while singing remains, especially with regard to distances, duration of singing, number of singers and their positions in the room, size of the room as well as ventilation strategies. Based on the assumption that CO2 is a suitable indicator for the exhaled aerosols in a room, it is the aim of this study to deduce recommendations for a choir rehearsal with a minimum risk of infection. METHODS: During two choir rehearsals in a typical, nonventilated classroom, we installed 30 CO2 sensors, which allow spatial and temporal evaluation of the CO2 dispersion during singing. Various singing and ventilation phases were applied and the rates of CO2 increase during singing as well as its decrease during ventilation phases were evaluated and compared for different scenarios. RESULTS: The measurements reveal a linear relation between the duration of singing, size of the room and number of persons. For our size of the room of 200 m3 the average CO2 increase is 1.83 ppm/min per person. Masks or pure breathing without singing do - in contrast to aerosol dispersion - not influence the rate of CO2 increase. CO2 disperses fast and homogeneously on horizontal planes. However, a vertical layering with a maximum CO2 concentration is observed near the ceiling. Shock ventilation shows the largest CO2 decrease within the first 5 min, after 10 min of ventilation the outside base concentration of 400 ppm is reached again. CONCLUSION: The evaluated relations allow to calculate safe singing times for a defined number of singers and size of the room until a critical threshold of 800 ppm is reached. Furthermore, in order to monitor the actual CO2 concentration during choir rehearsal, just one CO2 sensor is representative for the air quality and CO2 concentration of the whole room and thus considered sufficient. For an early warning, it should be installed near the ceiling. Direct singing into a sensor should be avoided. A ventilation time of just 5 min is recommended which represents a compromise between strong CO2 reduction and still sufficient room temperature during winter time.

Salivary Diagnostic for Monitoring Strenuous Exercise-A Pilot Study in a Cohort of Male Ultramarathon Runners.

Intense physical stress, such as that in ultramarathon running, affects the immune system. For monitoring in sports medicine, non-invasive methods, e.g., salivary analysis, are of interest. This pilot cohort study aimed to assess changes in salivary parameters in response to an ultramarathon. The results were compared to blood parameters. Male, healthy finishers (n = 9, mean age: 48 ± 8.8 years, mean height: 1.8 ± 0.1 m, mean weight: 72.5 ± 7.2 kg, mean BMI: 23.5 ± 1.9 kg/cm²) of a 160 km ultramarathon were included. Saliva and blood samples were collected at three time points: T1 (baseline), T2 (shortly after the ultramarathon) and T3 (after recovery). In saliva, cortisol, testosterone, IL-1ß, IL-6, IL-8, IL-10, TNF-α, albumin, IgA, α-amylase, aMMP-8, and neopterin were assessed via ELISA. In blood, cortisol, testosterone, IL-1ß, IL-6, IL-8, IL-10, TNF-α, blood cell counts, procalcitonin, CRP, osmolality, albumin, and α-amylase were analyzed. The statistical evaluation comprised longitudinal testing and cross-sectional testing between saliva and blood using ratios of T2 and T3 to baseline values. Various parameters in saliva and blood changed in response to the ultramarathon. Comparing blood and saliva, the longitudinal changes of testosterone (p = 0.02) and α-amylase (p = 0.03) differed significantly. Despite the limitations of the study, it underlines that saliva is an interesting option for comprehensive monitoring in sports medicine and necessitates further studies.

Comparative evaluation of two different Opuntia ficus-indica extracts for blood sugar lowering effects in rats.

Stems of Opuntia ficus-indica (L.) Mill. (OFI) are traditionally used in Mexico to treat diabetes mellitus. Less research data are available for combinations of stem and fruit preparations. The present study was designed to investigate the effects of an aqueous extract prepared from the cladodes and a proprietary stem/fruit skin-blend (stem/fruit skin ratio 75/25) of OFI on blood glucose and plasma insulin in normal rats. A dose finding study with the traditional cladode OFI extract revealed that maximum effects on blood glucose and insulin were observed after oral administration in a dose range of 6-176 mg/kg. The proprietary OFI blend significantly lowered blood glucose levels in the glucose tolerance test to a similar extent (p < 0.05 vs control) as the traditional aqueous cladode extract when administered in a dose of 6 mg/kg. In contrast to the aqueous extract, the proprietary blend significantly increased basal plasma insulin levels (p < 0.01 vs control) indicating a direct action on pancreatic beta cells. The results suggest that both OFI extracts exert hypoglycemic activities in rats in doses as low as 6 mg/kg but that the effects of the proprietary stem/fruit blend were more pronounced in our model.

Robotically assisted enhanced-view totally extraperitoneal repair (eTEP) of a recurrent umbilical hernia in a patient with peritoneal dialysis.

Background: Abdominal wall hernias are frequent in patients with peritoneal dialysis. Guidelines recommend an open hernia repair with extraperitoneal mesh placement to avoid access to the abdominal cavity. Method: We performed a lateral docking robotically assisted enhanced-view totally extraperitoneal repair (eTEP) of a recurrent umbilical hernia with diastasis recti in a patient with peritoneal dialysis due to polycystic kidney disease. After suturing of the midline a 20 x 28 cm mesh was placed in the retrorectus space, covering the whole area of preparation while also overlapping all trocar sites. A drainage was left in the retrorectus space until the first session of PD did not sample any form of leakage. Result: Robotically assisted totally extraperitoneal hernia repair was feasible. The patient was able to continue peritoneal dialysis without intermittent hemodialysis. There was no leakage of the dialysate to the retrorectus space. Postoperative recovery was uneventful. 6 months after surgery the patient was free from pain and showed no signs of recurrence. Conclusion: Robotically assisted totally extraperitoneal hernia repair in patients with umbilical hernia and peritoneal dialysis could be a promising surgical technique to combine the advantages of minimally-invasive surgery with totally extraperitoneal mesh placement without access to the abdominal cavity.

PDL1 expression on monocytes is associated with plasma cytokines in Tuberculosis and HIV.

INTRODUCTION: PDL1 and its interaction with PD1 is implicated in immune dysfunction in TB and HIV. The expression of PDL1 on multiple subsets of monocytes as well as their associations with cytokines and microbial products have not been well studied. METHOD: HIV (TB-HIV+), TB (TB+HIV-) and TB/HIV co-infected (TB+HIV+) patients as well as apparently healthy controls (TB-HIV-) were recruited. TB and HIV patients were treatment naïve while TB/HIV patients were both ART naïve and experienced but not yet started TB therapy. Monocyte subsets were evaluated for PDL1 expression by flow cytometry; plasma TNFα, IL6, IP10, IFNγ and IL10 were measured by Luminex; and cytokine mRNA from purified monocytes quantitated by qPCR. The association of PDL1 with cytokines, clinical and microbial indices, including HIV viral load, TB smear microscopy and TB urinary lipoarabinomannan (LAM) were assessed. RESULTS: Monocyte expression of PDL1 was significantly higher in TB, HIV and TB/HIV co-infected patients compared with healthy controls (p = 0.0001), with the highest levels in TB/HIV co-infected patients. The highest expression of PDL1 was on intermediate (CD14+CD16+) monocytes in all participant groups. PDL1 strongly correlated with HIV viral load in TB/HIV while weakly correlated in HIV. PDL1 levels moderately correlated with plasma TNFα, IL6, IP10, IFNγ and IL10 level in TB subjects whereas weakly correlated with TNFα and IP10 in HIV patients. However, cytokine mRNA from purified monocytes showed no association with either plasma cytokines or monocyte PDL1 expression, implying that if cytokines modulate PDL1, they are likely not originating from circulating monocytes themselves. These results underscore the importance of further characterization of multiple monocyte subsets and their phenotypic and functional differences in different disease states.

Impact of thymol in thyme extracts on their antispasmodic action and ciliary clearance.

Thyme is a herb with broncholytic und secretomotoric effects. Its activity on beta (2) receptors as a possible mechanism of action was demonstrated. Major components are thymol and carvacrol which are claimed to be responsible for its effects and, therefore, used for standardization in the German pharmacopoeia (0.03 % phenols calculated as thymol). Our aim was to investigate the impact of thymol by using thyme extracts with either normal or extremely low thymol concentrations (< 0.005 % or > 0.038 %). The antispasmodic effect on smooth muscles of the trachea and the ileum and the effect on ciliary activity (respiratory clearance) were investigated. In addition, pure thymol and carvacrol were investigated separately and in spiking experiments. Thymol and carvacrol had a concentration-dependent antispasmodic effect in the rat trachea either being stimulated by acetylcholine, K (+) or Ba (++). The same result was observed with respect to the increase of mucociliary transport in mice. Extracts with very low thymol contents are effective in all models used except acetylcholine-induced rat ileum contraction. When thyme extracts with normal thymol contents or with very low thymol contents were compared, the extract with normal thymol contents was more effective, both as a relaxant (rat ileum) and as an antispasmodic compound (rat trachea contraction induced by either acetylcholine, Ba (++) or K (+)) and in ciliary transport experiments. Thyme extracts with very low thymol contents (practically free of volatile oil) were equally effective with respect to endothelin effects. When an extract with very low thymol contents is spiked with increasing concentrations of thymol, a concentration-dependent increase concerning the antispasmodic effect (Ba (++)-induced trachea contraction) is observed. In conclusion, the data show that in various models of antispasmodic effect (ileum and trachea) and by measuring ciliary activity, thymol (and carvacrol) is (are) active, although other not identified components of thyme extract appear to be very important as well, since extracts with very low thymol contents are active. On the basis of these results the standardization on thymol alone appears not to be justified.

Perioperative chemotherapy for advanced gastric cancer - results from a tertiary-care hospital in Germany.

BACKGROUND: Neoadjuvant/perioperative chemotherapy is the recommended treatment for advanced stages of gastric cancer (> T2, N+) before tumour resection in many European guidelines. However, there is no consensus as to whether perioperative chemotherapy is as effective in distal as in proximal tumours, in addition to a relevant uncertainty concerning appropriate treatment modalities for elderly patients. AIM: To investigate the role of perioperative chemotherapy in advanced gastric cancer in patients from a German tertiary clinic with respect to efficacy, localisation, and age. METHODS: We performed a retrospective analysis of 158 patients from our clinic with adenocarcinoma of the stomach or the gastroesophageal junction who underwent resection between 2008 and 2016. The data were evaluated particularly in relation to patient age, tumour site, and perioperative therapy. RESULTS: Administration of perioperative chemotherapy did not lead to a significant survival advantage in our study population. The 5-year survival rates were 40% for patients who received perioperative chemotherapy and 29% for the group without perioperative chemotherapy (P = 0.125). Our patients were on average distinctly older than patients in most of the published randomised controlled trials. Patients elder than 75 years received perioperative chemotherapy far less frequently. Patients with a proximal tumour received perioperative chemotherapy much more often. CONCLUSION: This analysis reconfirms our previous data concerning the effectiveness of perioperative chemotherapy for advanced gastric cancer. There is reasonable doubt that the quality of the existing randomized controlled trials is sufficient to generally justify perioperative chemotherapy in patients with advanced gastric cancer independent of tumour localization or age.