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1.

Background

Congenital malformations of the seminal vesicle are uncommon, and most of them are cystic malformations. If an insult occurs between the 4th and the 13 h gestational week, the embryogenesis of the kidney, ureter, seminal vesicle, and vas deferens could be altered. Cysts of the seminal vesicle may appear with a mass effect, dysuria, epididymitis, or obstruction of the gastrointestinal and genitourinary tracts. Approximately two thirds of them are associated with ipsilateral renal agenesis, because both the ureteral buds and seminal vesicles originate from the mesonephric (Wolffian) duct. They were first described by Zinner in 1914, and 200 cases of seminal vesicle cysts associated with ipsilateral renal agenesis have been reported in the literature. Most patients with this anomaly are asymptomatic until the third or fourth decade of life. Some cases have nonspecific symptoms such as prostatism, urinary urgency, dysuria, painful ejaculation, and perineal discomfort. Transrectal ultrasonography provides good visualization of the pelvic structures and allows guidance for aspiration of the cysts.

Case presentation

We present two cases of seminal vesicle cyst. The first patient had dysuria, increased frequency of urination, and haematuria. He was operated and benefited from a removal of the cyst with right ureterectomy and left ureteral reimplantation. The second patient had disorder of the digestive transit and he benefited from a laparoscopic removal of the cyst.

Conclusions

Seminal vesicle cysts combined with ipsilateral renal agenesis are rare urological anomalies. Usual symptoms that are caused by the seminal vesicle cysts are bladder irritation and obstruction as well as pain in the perineum and scrotum. Epididymitis is frequently found. Treatment consists to removing the seminal vesicle cyst.
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2.

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.
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3.

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.
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4.

Introduction

Endometriosis is an estrogen-dependent gynecological disease that causes infertility, and potential metabolomic biomarkers related to ovarian endometriosis and poor outcomes after assisted reproductive treatments are still lacking.

Objectives

The present study analyzed the metabolomic profiling of follicular fluid samples from 40 patients undergoing in vitro fertilization.

Methods

The follicular fluid samples were classified as controls (n = 22) and endometriosis patients (n = 18). The samples were submitted to Bligh and Dyer protocol followed by metabolomics analysis by ultra-performance liquid chromatography mass spectrometry. Clinical data was assessed by Students’ T-test and metabolomics data was analyzed by multivariate statistics by MetaboAnalyst 3.0 to obtain intrinsic characteristics that allowed for groups discrimination. The Receiver Operating Characteristic curve was carried out for the proposed biomarkers, aiming to determine their specificity and sensitivity, as a set and individually.

Results

From the metabolomic analysis, 20 ion masses were selected as potential biomarkers from principal component analysis, which showed that all biomarkers were more abundant in the endometriosis group when compared to controls. Tentative attribution was performed by lipid maps database, demonstrating that these potential biomarkers correspond to fatty acids, carnitines, monoacylglycerols, lysophosphatidic acids, lysophosphatidylglycerols, diacylglycerols, lysophosphatidylcholines, phosphatidylserine, lysophosphatidylinositols and Phosphatidic Acid.

Conclusion

The use of mass spectrometry-based metabolomics allowed for the identification of effective biomarkers for ovarian endometriosis, which may contribute for a better comprehension of the disease and how it affects the ovary, as well as assisting in the development of accessory tools for endometriosis diagnosis and infertility management.
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5.

Background

It has previously been shown that the morphology of the P-wave neither depends on atrial size in healthy subjects with physiologically enlarged atria nor on the physiological anatomical variation in transverse orientation of the left atrium. The present study aimed to investigate if different pressures in the left and right atrium are associated with different P-wave morphologies.

Methods

38 patients with isolated, increased left atrial pressure, 51 patients with isolated, increased right atrial pressure and 76 patients with biatrially increased pressure were studied. All had undergone right heart catheterization and had 12-lead electrocardiographic recordings, which were transformed into vectorcardiograms for detailed P-wave morphology analysis.

Results

Normal P-wave morphology (type 1) was more common in patients with isolated increased pressure in the right atrium while abnormal P-wave morphology (type 2) was more common in the groups with increased left atrial pressure (P = 0.032). Moreover, patients with increased left atrial pressure, either isolated or in conjunction with increased right atrial pressure, had significantly more often a P-wave morphology with a positive deflection in the sagittal plane (P = 0.004).

Conclusion

Isolated elevated right atrial pressure was associated with normal P-wave morphology while left-sided atrial pressure elevation, either isolated or in combination with right atrial pressure elevation, was associated with abnormal P-wave morphology.
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6.

Introduction

Aqueous–methanol mixtures have successfully been applied to extract a broad range of metabolites from plant tissue. However, a certain amount of material remains insoluble.

Objectives

To enlarge the metabolic compendium, two ionic liquids were selected to extract the methanol insoluble part of trunk from Betula pendula.

Methods

The extracted compounds were analyzed by LC/MS and GC/MS.

Results

The results show that 1-butyl-3-methylimidazolium acetate (IL-Ac) predominantly resulted in fatty acids, whereas 1-ethyl-3-methylimidazolium tosylate (IL-Tos) mostly yielded phenolic structures. Interestingly, bark yielded more ionic liquid soluble metabolites compared to interior wood.

Conclusion

From this one can conclude that the application of ionic liquids may expand the metabolic snapshot.
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7.

Background

Renal cell carcinoma is well known for its frequency to metastasise, particularly to lungs, liver, bones and brain. Metastasis to the skin is much less common. Presentation as a result of the skin lesion is even more unusual, with only 14 previously reported cases in the English literature. The majority of these cases have been reported in patients with recurrent disease or with other metastases.

Case presentation

We present only the second case of non-recurrent renal cell carcinoma with a solitary cutaneous facial metastasis reported in the English literature.

Conclusion

Clinicians should conduct a careful inspection of the skin in patients with renal cell carcinoma and also have a high index of suspicion of primary internal organ malignancy in patients presenting with a skin lesion.
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8.

Introduction

Botanicals containing iridoid and phenylethanoid/phenylpropanoid glycosides are used worldwide for the treatment of inflammatory musculoskeletal conditions that are primary causes of human years lived with disability, such as arthritis and lower back pain.

Objectives

We report the analysis of candidate anti-inflammatory metabolites of several endemic Scrophularia species and Verbascum thapsus used medicinally by peoples of North America.

Methods

Leaves, stems, and roots were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and partial least squares-discriminant analysis (PLS-DA) was performed in MetaboAnalyst 3.0 after processing the datasets in Progenesis QI.

Results

Comparison of the datasets revealed significant and differential accumulation of iridoid and phenylethanoid/phenylpropanoid glycosides in the tissues of the endemic Scrophularia species and Verbascum thapsus.

Conclusions

Our investigation identified several species of pharmacological interest as good sources for harpagoside and other important anti-inflammatory metabolites.
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9.

Introduction

Concerning NMR-based metabolomics, 1D spectra processing often requires an expert eye for disentangling the intertwined peaks.

Objectives

The objective of NMRProcFlow is to assist the expert in this task in the best way without requirement of programming skills.

Methods

NMRProcFlow was developed to be a graphical and interactive 1D NMR (1H & 13C) spectra processing tool.

Results

NMRProcFlow (http://nmrprocflow.org), dedicated to metabolic fingerprinting and targeted metabolomics, covers all spectra processing steps including baseline correction, chemical shift calibration and alignment.

Conclusion

Biologists and NMR spectroscopists can easily interact and develop synergies by visualizing the NMR spectra along with their corresponding experimental-factor levels, thus setting a bridge between experimental design and subsequent statistical analyses.
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10.

Background

A distended, mucous-filled appendix is known as an appendiceal mucocele. They are a rare form of an appendiceal mass and develop from both benign and malignant processes. Mucoceles can develop secondarily to an obstruction, such as from a fecalith, scarring or, rarely, endometriosis. Only 12 cases of non-neoplastic appendiceal mucoceles caused by endometriosis have been previously described. The association between neoplastic appendiceal mucoceles in the presence of endometriosis is described for the first time in this report.

Case presentation

A 57-year-old woman presented with a chief complaint of worsening abdominal pain over the past 3 months. Imaging studies revealed an appendiceal mass. Laparoscopic evaluation confirmed an appendiceal mucocele, and the patient underwent complete appendectomy. No evidence of mucinous or endometrial deposits were present within the abdominal cavity. Pathological diagnosis revealed low-grade appendiceal mucinous neoplasm (LAMN) with evidence of endometriosis within the muscularis propria of the appendix. The patient recovered without complications and her abdominal pain completely resolved.

Conclusions

Endometriosis of the appendix is a rare manifestation and is most often identified as an incidental finding. Endometriosis leading to an obstructive mucocele of the appendix is an exceedingly rare finding, having only been described 12 times in the medical literature. LAMN in the presence of endometriosis of the appendix is described for the first time in this report. The association between appendiceal neoplasms in the presence of endometriosis requires further research in order to optimize operative treatment.
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11.

Introduction

Although current immunosuppressive protocols have dramatically improved 1-year survival of kidney transplants, there has been less progress in terms of long-term graft survival over the last two decades. The key to avoiding late graft loss is early diagnosis and differentiation between anti-allograft immune processes and immunosuppressant toxicity (IS-Tox). Modern bioanalytical technologies have opened new opportunities for the development of sensitive and specific diagnostic tools. There is an immediate need for biomarkers that are able to differentiate between renal allograft rejection and immunosuppressant toxicity.

Objective

To test our hypothesis that changes of metabolite patterns in urine have the potential to serve as a non-invasive combinatorial biomarker that can differentiate between allograft immune reactions and IS-Tox.

Methods

We used 1H-NMR spectroscopy and Luminex multiplexing for metabolic profiling of rat urine and the analysis of protein biomarkers in urine and plasma, respectively, to compare the effects of chronic allograft rejection in a Fisher-to-Lewis rat transplant model with IS-Tox induced by cyclosporine, tacrolimus and/or sirolimus in Lewis rats.

Results

Our results showed that, while IS-Tox caused changes in metabolite patterns that are typically associated with proximal tubule damage, rejection caused more profuse changes not specifically focused on a particular kidney region. Moreover, metabolite pattern changes were more sensitive than changes in protein markers that were evident only during the later stages of rejection.

Conclusion

The present study provides first proof-of-concept that longitudinal monitoring of urine metabolite markers has the potential to differentiate between early renal allograft rejection and immunosuppressant nephrotoxicity.
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12.

Background

Renal oncocytomas (ROs) are benign epithelial tumors of the kidney whereas chromophobe renal cell carcinoma (chRCCs) are malignant renal tumors. The latter constitute 5–7% of renal neoplasias. ROs and chRCCs show pronounced molecular and histological similarities, which renders their differentiation demanding. We aimed for the differential proteome profiling of ROs and early-stage chRCCs in order to better understand distinguishing protein patterns.

Methods

We employed formalin-fixed, paraffin-embedded samples (six RO cases, six chRCC cases) together with isotopic triplex dimethylation and a pooled reference standard to enable cohort-wide quantitative comparison. For lysosomal-associated membrane protein 1 (LAMP1) and integrin alpha-V (ITGAV) we performed corroborative immunohistochemistry (IHC) in an extended cohort of 42 RO cases and 31 chRCC cases.

Results

At 1% false discovery rate, we identified?>?3900 proteins, of which?>?2400 proteins were consistently quantified in at least four RO and four chRCC cases. The proteomic expression profiling discriminated ROs and chRCCs and highlighted established features such as accumulation of mitochondrial proteins in ROs together with emphasizing the accumulation of endo-lysosomal proteins in chRCCs. In line with the proteomic data, IHC showed enrichment of LAMP1 in chRCC and of ITGAV in RO.

Conclusion

We present one of the first differential proteome profiling studies on ROs and chRCCs and highlight differential abundance of LAMP1 and ITGAV in these renal tumors.
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13.

Introduction

The chemical sensitivity of urine metabolomics analysis is greatly compromised due to the large amounts of inorganic salts in urine (NaCl, KCl), which are detrimental to analytical instrumentation, e.g. chromatographic columns or mass spectrometers. Traditional desalting approaches applied to urine pretreatment suffer from the chemical losses, which reduce the information depth of analysis.

Objectives

We aimed to test a simple approach for the simultaneous preconcentration and desalting of organic solutes in urine based on the collection of induced bursting bubble aerosols above the surface of urine samples.

Method

Bursting bubbles were generated at ambient conditions by feeding gas through an air diffuser at the bottom of diluted (200 times in ultrapure water) urine solution (50–500 mL). Collected aerosols were analyzed by the direct-infusion electrospray ionization mass spectrometry (ESI–MS).

Results

The simultaneous preconcentration (ca. 6–12 fold) and desalting (ca. six–tenfold) of organic solutes in urine was achieved by the bursting bubble sample pretreatment, which allowed ca. three-times higher number of identified urine metabolites by high-resolution MS analysis. No chemical losses due to bubbling were observed. The increased degree of MS data clustering was demonstrated on the principal component analysis of data sets from the urine of healthy people and from the urine people with renal insufficiency. At least ten times higher sensitivity of trace drug detection in urine was demonstrated for clenbuterol and salbutamol.

Conclusion

Our results indicate the high versatility of bubble bursting as a simple pretreatment approach to enhance the chemical depth and sensitivity of urine analysis. The approach could be attractive for personalized medicine as well as for the diagnostics of renal disorders of different etiology (diabetic nephropathy, chronic renal failure, transplant-associated complications, oncological disorders).

Graphical Abstract

Urine desalting and preconcentration in bursting bubbles.
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14.

Introduction

Allograft rejection is still an important complication after kidney transplantation. Currently, monitoring of these patients mostly relies on the measurement of serum creatinine and clinical evaluation. The gold standard for diagnosing allograft rejection, i.e. performing a renal biopsy is invasive and expensive. So far no adequate biomarkers are available for routine use.

Objectives

We aimed to develop a urine metabolite constellation that is characteristic for acute renal allograft rejection.

Methods

NMR-Spectroscopy was applied to a training cohort of transplant recipients with and without acute rejection.

Results

We obtained a metabolite constellation of four metabolites that shows promising performance to detect renal allograft rejection in the cohorts used (AUC of 0.72 and 0.74, respectively).

Conclusion

A metabolite constellation was defined with the potential for further development of an in-vitro diagnostic test that can support physicians in their clinical assessment of a kidney transplant patient.
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15.

Background

There are few in-flight studies of cognition-related cerebral oxygen status in helicopter pilots.

Methods

Four male helicopter pilots volunteered for nine sorties during visual flight in a BK117 and UH-60J. The pilots' pre-frontal oxy-hemoglobin (O2Hb) and deoxy-hemoglobin (HHb) concentration were continuously monitored from the right/left sections of the forehead using near-infrared spectrophotometers with a consideration of motion artifacts.

Results

The concentration of O2Hb progressively increased (13.98 μmol?L-1 as a maximum increased concentration) in both the right/left sections of the forehead from the basal level during the heightened cognitive demand of helicopter flight. There was comparatively little change (4.32 μmol?L-1 as a maximum increased concentration) in HHb concentration during measurement of helicopter flight. HHb changes were apparently not affected by a heightened cognitive demand of helicopter pilots.

Conclusion

These results demonstrate that near-infrared spectroscopy, especially O2Hb measurements, provides a sensitive method for the monitoring of cognitive demand (maneuvers) in helicopter pilots.
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16.

Objective

The objective of this study is to systematically assess the clinical efficacy of hand-assisted laparoscopic surgery (HALS) and laparoscopic right colectomy (LRC).

Methods

The randomized controlled trials (RCTs) and non-RCTs were collected by searching electronic databases (Pubmed, Embase, and the Cochrane Library). The outcomes included intraoperative outcomes, postoperative outcomes, postoperative morbidity, and oncologic outcomes. Meta-analysis was performed using of RevMan 5.3 software.

Results

A total of five studies involving 438 patients were finally included, with 202 cases in HALS group and 236 cases in LRC group. Results of meta-analysis showed that there was no statistical difference between HALS and LRC in terms of conversion rate, length of hospital stay, reoperation rate, postoperative morbidity, and oncologic outcomes. The operative time was 6.5 min shorter in HALS group; however, it was not a clinically significant difference. Although the incision length was longer in HALS, it did not influence the postoperative recovery.

Conclusions

HALS can be considered an alternative to LRC which combines the advantages of open as well as laparoscopic surgery.
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17.

Background

Performing electrocardiography is common in general practice, but the quality of indication setting and diagnostic accuracy have been disputed.

Objectives

To assess the competence of general practitioners (GPs) in their decision-making process with regard to recording and interpreting an electrocardiogram (ECG) and evaluating the relevance of the result for management.

Methods

An online case vignette survey was performed among GPs and cardiologists (in 2015). Nine cases describing situations for which Dutch clinical guidelines recommend or advise against recording an ECG were presented. In each case, the participant had to make choices on recording an ECG, interpreting it, and using the result in a management decision. The reference standard for each ECG diagnosis was set by the expert author team.

Results

Fifty GPs who interpret ECGs themselves, eight GPs who do not and 12 cardiologists completed the survey. Adherence to guidelines recommending an ECG was high for suspected atrial fibrillation, suspected arrhythmia present during consultation, including bradycardia, but much lower for progressive heart failure and stable angina. Diagnostic accuracy of GPs was best in atrial fibrillation (96%), sick sinus syndrome (85%) and old myocardial infarction (82%), but poor in left anterior fascicular block (16%) and incomplete right bundle branch block (10%). GPs often acknowledged the low relevance of the results of a non-indicated ECG.

Conclusion

GPs do not fully adhere to Dutch cardiovascular guidelines on indications for recording ECGs. Diagnostic accuracy was high for atrial fibrillation, sick sinus syndrome and old myocardial infarction and poor for left anterior fascicular block and incomplete right bundle branch block.
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18.

Background

The protein encoded by the gene ybgI was chosen as a target for a structural genomics project emphasizing the relation of protein structure to function.

Results

The structure of the ybgI protein is a toroid composed of six polypeptide chains forming a trimer of dimers. Each polypeptide chain binds two metal ions on the inside of the toroid.

Conclusion

The toroidal structure is comparable to that of some proteins that are involved in DNA metabolism. The di-nuclear metal site could imply that the specific function of this protein is as a hydrolase-oxidase enzyme.
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19.

Background

Until recently, plant metabolomics have provided a deep understanding on the metabolic regulation in individual plants as experimental units. The application of these techniques to agricultural systems subjected to more complex interactions is a step towards the implementation of translational metabolomics in crop breeding.

Aim of Review

We present here a review paper discussing advances in the knowledge reached in the last years derived from the application of metabolomic techniques that evolved from biomarker discovery to improve crop yield and quality.

Key Scientific Concepts of Review

Translational metabolomics applied to crop breeding programs.
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20.

Background

Pseudomyxoma peritonei is a rare condition consisting of mucinous ascites, most commonly arising from mucinous tumors of the appendix and occasionally from the ovary. Very rarely mucinous implants arise in the retroperitoneum without any intra-peritoneal involvement. This has been termed as pseudomyxoma extraperitonei.

Case presentation

We report a case of a 57 year old man who developed pseudomyxoma extraperitonei, 35 years after undergoing an appendicectomy for a perforated appendix.

Conclusions

Pseudomyxoma extraperitonei has been previously reported, however we report the longest incubation period of 35 years for this condition.
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