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The authors explain why accurate conclusions on public procurement efficiency are impossible in light of the current formal rules of the public contractual system. In regulatory acts, efficiency is replaced with saving and effectiveness - concepts that have different meaning and do not focus on the scale of transaction costs associated with contract conclusion and execution. Since assessing public procurement efficiency has no economic meaning outside the interests of particular actors, achieving the indicators specified in the Budget Code of the Russian Federation is not indicative of the desirable vector of development and result interpretation. In this case, control over efficient satisfaction of public needs is replaced with attaining the metrics (pseudo-objectives) and procedural compliance, which increases the regulator' influence. Multiple control parameters lead to adverse selection of the stuff of customer's contractual services and affect the quality of procured goods. Quasi- market competition based on directive buyer- seller interaction gives the appearance of fair transactions but does not stimulate efficiency or saving of public financial resources against transaction costs. Fair procedures designed to protect competitors from each other do not allow to build up trust-based interactions within the contractual system and engage supplier's reputation as well as establish long-term economic relations. To further develop the contractual system in Russia, would be useful to have a legal definition of public procurement efficiency and give the criteria for achieving it or rejecting procedural regulation.

The paper provides the rationale for using the public contractual system of the Russian Federation as a mechanism of a proactive economic policy. A number of works are analyzed that consider expenditure stimulation through a public contractual system as the main regulatory tool, for instance, in building national innovative systems, advancing research and technology, modeling the structure of the economy as well as solving social problems. An empirical analysis of the role of the Russian contractual system is given in view of its impact upon development of the regional economies in 2012–2019. Regular significant relations between the scope of financing public procurement within the contractual system of the Russian Federation and adequate own funds in the regional budgets are confirmed. The trends in elasticity coefficients characterizing correlations between the scope of financing of public and municipal procurement within the Russian public contractual system and particular tax groups in consolidated budgets of the subjects of the Russian Federation in 2012–2019 indicate economic appropriateness of increased procurement costs in terms of simultaneously providing own funds to the budgets. A positive influence of public and municipal procurement upon the level of employment and innovative activity of entities is shown, verifying, therefore, the potential of the Russian contractual system to support social and innovative policy, which is consistent with international evaluations. Conclusions are reached on the expediency of employing the budget and contractual system cumulatively as a proactive mechanism of economic policy to achieve efficient economic orders.

Objective: The aim of this study was to investigate the gut microbial signatures and related pathophysiological implications in patients with Cushing's disease (CD)., Design and Methods: Twenty-seven patients with CD and 45 healthy controls were enrolled. Based on obtained metagenomics data, we performed correlation, network study, and genome interaction group (GIG) analysis. Fecal metabolomics and serum enzyme linked immunosorbent assay (ELISA) analysis were conducted in dichotomized CD patients. Caco-2 cells were incubated with gradient concentrations of cortisol for subsequent transepithelial electrical resistance (TEER) measurement, FITC-dextran transwell permeability assay, qPCR, and western blot analysis., Results: Gut microbial composition in patients with CD was notably different from that in healthy controls. Network analysis revealed that Eubacterium siraeum might serve as the core specie in the gut microbial system of CD patients. Subsequent GIG analysis identified the positive correlations between GIG9 and UFC. Further serum ELISA and fecal metabolomics uncovered that CD patients with elevated UFC levels were characterized with increased lipopolysaccharide binding protein (LBP). Moreover, remarkable positive association was found between LBP level and relative abundance of E. siraeum. TEER and FITC-dextran transwell assays demonstrated that hypercortisolism induced increased gut permeability. Further qPCR and western blot analysis suggested that dysregulated AhR/Claudin 2 axis might be involved in the development of hypercortisolism-induced defective gut barrier function., Conclusions: Disease activity associated dysbiosis and defective gut barrier might jointly facilitate the development of systemic inflammation in patients with CD., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Craniopharyngioma (CP) is an intracranial tumor with high mortality and morbidity. Though biologically benign, CP will damage the hypothalamus, inducing comorbidities such as obesity, metabolic syndrome, and cognitive impairments. The roles of gut microbiome and serum metabolome in CP-associated hypothalamic comorbidities are aimed to be explored. Patients with CP are characterized by increased Shannon diversity, Eubacterium, Clostridium, and Roseburia, alongside decreased Alistipes and Bacteroides. CP-enriched taxa are positively correlated with dyslipidemia and cognitive decline, while CP-depleted taxa are negatively associated with fatty liver. Subsequent serum metabolomics identified notably up-regulated purine metabolism, and integrative analysis indicated an association between altered microbiota and elevated hypoxanthine. Phenotypic study and multi-omics analysis in the Rax-CreER T2 ::Braf V600E/+ ::Pten Flox/+ mouse model validated potential involvement of increased Clostridium and dysregulated purine metabolism in hypothalamic comorbidities. To further consolidate this, intervention experiments are performed and it is found that hypoxanthine co-variated with the severity of hypothalamic comorbidities and abundance of Clostridium, and induced dysregulated purine metabolism along with redox imbalance in target organs (liver and brain cortex). Overall, the study demonstrated the potential of increased Clostridium and up-regulated purine metabolism as signatures of CP-associated hypothalamic-comorbidities, and unveiled that elevated Clostridium, dysregulated purine metabolism, and redox imbalance may mediate the development and progression of CP-associated hypothalamic-comorbidities., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Purpose: Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of growth hormone and insulin-like growth factor 1, causing increased morbidity and mortality. Previous studies have investigated the transcription of GHPA. However, the gene regulatory landscape has not been fully characterized. The objective of our study was to unravel the changes in chromatin accessibility and transcription in GHPA., Methods: Six patients diagnosed with GHPA in the Department of Neurosurgery at Huashan Hospital were enrolled in our study. Primary pituitary adenoma tissues and adjacent normal pituitary specimens with no morphologic abnormalities from these six patients were obtained at surgery. RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were applied to investigate the underlying relationship between gene expression and chromatin accessibility changes in GHPA., Results: Totally, 1528 differential expression genes (DEGs) were identified by transcriptomics analyses, including 725 up-regulated and 803 down-regulated. Further, we obtained 64 significantly DEGs including 10 DEGs were elevated and 54 DEGs were negligibly expressed in tumors tissues. The up-regulated DEGs were mainly involved in terms related to synapse formation, nervous system development and secretory pathway. In parallel, 3916 increased and 2895 decreased chromatin-accessible regions were mapped by ATAC-seq. Additionally, the chromatin accessible changes were frequently located adjacent to transcription factor CTCF and Rfx2 binding site., Conclusions: Our results are the first to demonstrate the landscape of chromatin accessibility in GHPA, which may contribute to illustrate the underlying transcriptional regulation mechanism of this disease., (© 2022. The Author(s).)

Prior study has demonstrated that gut microbiota at the genus level is significantly altered in patients with growth hormone (GH)-secreting pituitary adenoma (GHPA). Yet, no studies exist describing the state of gut microbiota at species level in GHPA. We performed a study using 16S rRNA amplicon sequencing in a cohort of patients with GH-secreting pituitary adenoma (GHPA, n  = 28) and healthy controls ( n  = 67). Among them, 9 patients and 10 healthy controls were randomly chosen and enrolled in metagenomics shotgun sequencing, generating 280,426,512 reads after aligning to NCBI GenBank DataBase to acquire taxa information at the species level. Weighted UniFrac analysis revealed that microbial diversity was notably decreased in patients with GHPA, consistent with a previous study. With 16S rRNA sequencing, after correction for false-discovery rate (FDR), rank-sum test at the genus level revealed that the relative abundance of Oscillibacter and Enterobacter was remarkably increased in patients and Blautia and Romboutsia genera predominated in the controls, augmented by additional LEfSe (linear discriminant analysis effect size) analysis. As for further comparison at the species level with metagenomics sequencing, rank-sum test together with LEfSe analysis confirmed the enrichment of Alistipes shahii and Odoribacter splanchnicus in the patient group. Notably, LEfSe analysis with metagenomics also demonstrated that Enterobacter sp. DC1 and Enterobacter sp. 940 PEND , derived from Enterobacter , were both significantly enriched in patients. Functional analysis showed that amino acid metabolism pathway was remarkably enriched in GHPA, while carbohydrate metabolism pathway was notably enriched in controls. Further, significant positive correlations were observed between Enterobacter and baseline insulin-like growth factor 1 (IGF-1), indicating that Enterobacter may be strongly associated with GH/IGF-1 axis in GHPA. Our data extend our insight into the GHPA microbiome, which may shed further light on GHPA pathogenesis and facilitate the exploration of novel therapeutic targets based on microbiota manipulation. IMPORTANCE Dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extraintestinal diseases. Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of GH and IGF-1, causing increased morbidity and mortality. Researches have reported that the GH/IGF-1 axis exerts its own influence on the intestinal microflora. Here, the results showed that compared with healthy controls, GHPA patients not only decreased the alpha diversity of the intestinal flora but also significantly changed their beta diversity. Further, metagenomics shotgun sequencing in the present study exhibited that Enterobacter sp. DC1 and Enterobacter sp. 940 PEND were enriched in patients. Also, we were pleasantly surprised to find that the Enterobacter genus was strongly positively correlated with baseline IGF-1 levels. Collectively, our work provides the first glimpse of the dysbiosis of the gut microbiota at species level, providing a better understanding of the pathophysiological process of GHPA.

Rosiglitazone, a synthetic peroxisome proliferator-activated receptor γ (PPARγ) ligand, has been reported to reduce growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in 10 patients with acromegaly. However, the mechanisms remain unknown. Here, we reveal that PPARγ directly enhances 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression, whose expression is decreased and negatively correlates with tumor size in acromegaly. Rosiglitazone decreases GH production and promotes apoptosis and autophagy in GH3 and primary somatotroph adenoma cells and suppresses hepatic GH receptor (GHR) expression and IGF-1 secretion in HepG2 cells. Activating the PGE2/cAMP/PKA pathway directly increases GHR expression. Rosiglitazone suppresses tumor growth and decreases GH and IGF-1 levels in mice inoculated subcutaneously with GH3 cells. The above effects are all dependent on 15-PGDH expression. Rosiglitazone as monotherapy effectively decreases GH and IGF-1 levels in all nineteen patients with active acromegaly. Evidence suggests that rosiglitazone may be an alternative pharmacological approach for acromegaly by targeting both pituitary adenomas and liver., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

In 2016, an outbreak of anthrax killing thousands of reindeer and affecting dozens of humans occurred on the Yamal peninsula, Northwest Siberia, after 70 years of epidemiological situation without outbreaks. The trigger of the outbreak has been ascribed to the activation of spores due to permafrost thaw that was accelerated during the summer heat wave. The focus of our study is on the dynamics of local environmental factors in connection with the observed anthrax revival. We show that permafrost was thawing rapidly for already 6 years before the outbreak. During 2011-2016, relatively warm years were followed by cold years with a thick snow cover, preventing freezing of the soil. Furthermore, the spread of anthrax was likely intensified by an extremely dry summer of 2016. Concurrent with the long-term decreasing trend in the regional annual precipitation, the rainfall in July 2016 was less than 10% of its 30-year mean value. We conclude that epidemiological situation of anthrax in the previously contaminated Arctic regions requires monitoring of climatic factors such as warming and precipitation extremes., (© 2021. The Author(s).)

Acromegaly presents with an enigmatic range of symptoms and comorbidities caused by chronic and progressive growth hormone elevations, commonly due to endocrinologic hypersecretion from a pituitary gland tumor. Comprehensive national acromegaly databases have been appearing over the years, allowing for international comparisons of data, although still presenting varying prevalence and incidence rates. Lack of large-scale analysis in geographical and ethnic differences in clinical presentation and management requires further research. Assessment of current and novel predictors of responsiveness to distinct therapy can lead to multilevel categorization of patients, allowing integration into new clinical guidelines and reduction of increased morbidity and mortality associated with acromegaly. This review compares current data from epidemiological studies and assesses the present-day application of prognostic factors in medical practice, the reality of precision therapy, as well as its future prospects in acromegaly, with a special focus on its relevance to the South Korean population.

Context: Metabolic disorders, especially dysregulated lipid metabolism, increase the risk of cardiovascular mortality in acromegaly. Previous studies measuring plasma macromolecular lipids have yielded conflicting results., Purpose: To explore the plasma lipid metabolite profiles by metabolomics analysis and identify potential metabolites associated with cardiac function in acromegaly., Methods: Plasma was obtained from 80 newly diagnosed, untreated patients with acromegaly and 80 healthy controls. Echocardiography was performed. Based on the results of an oral glucose tolerance test (OGTT), patients were categorized into 2 groups: normal glucose tolerance (NGT, n = 28) and impaired glucose tolerance or diabetes mellitus (IGT/DM, n = 52). High-performance liquid chromatography-mass spectrometry (HPLC-MS)-based metabolomics analysis was conducted. Data were processed by principal components analysis (PCA), orthogonal partial least square-discriminant analysis (OPLS-DA), and MetaboAnalyst 4.0. Associations between metabolic substances and cardiovascular parameters were also explored., Results: Metabolomics uncovered a distinct metabolic pattern between acromegaly and healthy controls, and perturbed pathways mainly include glycerophospholipid metabolism, sphingolipid metabolism, as well as linoleic acid metabolism. Collective analysis showed that phosphatidylethanolamine (PE) (22:6/16:0) was positively correlated with LV mass, while lysophosphatidylcholine (LysoPC) (16:0) was positively correlated with fractional shortening (FS) and left ventricle ejection fraction (LVEF)., Conclusion: Patients with acromegaly have distinct lipid metabolite profiling, while PE (22:6/16:0) and LysoPC (16:0) are correlated with cardiac structure and function, which may contribute to the risk of cardiovascular complications., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Morbidly obese patients undergoing general anesthesia for laparoscopic bariatric surgery are considered at increased risk of a postoperative decrease in lung function. The purpose of this study was to determine whether a systematic use of incentive spirometry (IS) prior to surgery could help patients to preserve their respiratory function better in the postoperative period. Forty-one morbidly obese (body mass index [BMI] > 40 kg/m²) candidates for laparoscopic bariatric surgery were consented in the study. All patients were taught how to use an incentive spirometer but then were randomized blindly into 2 groups. The control group was instructed to use the incentive spirometer for 3 breaths, once per day. The treatment group was requested to use the incentive spirometer for 10 breaths, 5 times per day. Twenty experimental (mean BMI of 48.9 ± 5.67 kg/m²) and 21 control patients (mean BMI of 48.3 ± 6.96 kg/m²) were studied. The initial mean inspiratory capacity (IC) was 2155 ± 650.08 (SD) cc and 2171 ± 762.98 cc in the experimental and control groups, respectively. On the day of surgery, the mean IC was 2275 ± 777.56 cc versus 2254.76 ± 808.84 cc, respectively. On postoperative day 1, both groups experienced a significant drop of their IC, with volumes of 1458 ± 613.87 cc (t test P < 0.001) and 1557.89 ± 814.67 cc (t test P < 0.010), respectively. Our results suggest that preoperative use of the IS does not lead to significant improvements of inspiratory capacity and that it is a not a useful resource to prevent postoperative decrease in lung function., (Copyright © 2010 Mosby, Inc. All rights reserved.)

A new positioning device, the Rapid Airway Management Positioner (RAMP, Airpal Inc., Center Valley, PA) was evaluated to determine if there was an improvement in either mask ventilation, direct laryngoscopy, or both with the use of the RAMP in this patient population. Fifty-one morbidly obese patients (BMI > 35 kg/m(2)) undergoing elective bariatric surgery were enrolled. Ventilation and laryngoscopy was performed in the neutral and head-elevated laryngoscopy position (HELP). Direct laryngoscopy was performed noting the glottic view according to the Cormack-Lehane classification (Samsoon and Young, Anesthesiology 42:487, 1987). Mask ventilation was then recommenced. The HELP, or "ramped," position was achieved by inflating the RAMP, which was placed underneath the patient prior to entering the OR. Once proper HELP position was achieved, a second laryngoscopy was performed followed by endotracheal intubation. Two main outcomes were noted in the neutral and HELP positions: (1) laryngoscopic view and (2) ease of ventilation. The inflated ramped position provided greater ease of ventilation as compared to the neutral position (p = 0.0003). There was also a significant improvement in the glottic view in the ramped position (p = 0.04). Ease of intubation was perceived to be severely difficult among two, and overall use of the positioning device was found to be difficult among seven of the residents. The RAMP effectively positions morbidly obese patients in the HELP position. Ease of ventilation and laryngoscopic view were both improved with its use in this patient population.

Objectives: Little is known about the rates of congenital anomalies in the northernmost regions of the world. As in other parts of the world, it is crucial to assess the relative rates and trends of adverse birth outcomes and birth defects, as indicators of population health and to develop public health strategies for prevention. The aim of this review is to catalogue existing and developing birth outcome and birth defect surveillance within and around the geographic jurisdiction of the International Union of Circumpolar Health (IUCH)., Study Design: Descriptive study., Methods: The representatives of the IUCH Birth Defects Working Group catalogued existing and developing birth and birth defect surveillance systems and the extent of information they contain to determine inter-regional comparability., Results: Systematic population-based registration of birth outcomes including birth defects occurs to some degree in all circumpolar countries, but the quality of collection and the coverage in northernmost regions vary. There are limited circumpolar jurisdictions with surveillance systems collecting birth defect information beyond the perinatal period. Efforts are underway in Canada and Russia to improve the quality and comprehensiveness of the information collected in the northern regions., Conclusions: Although there is variability in the comprehensiveness of information collected in northern jurisdictions limiting sophisticated comparative analyses between regions, there is untapped potential for baseline analyses of specific risks and outcomes that could provide insight into geographic differences and gaps in surveillance that could be improved.

Background: Electrocardiogram (ECG) guidance to confirm accurate positioning of central venous catheters (CVC), placed before surgery in the operating room, is rarely used in the United States. We designed this randomized, controlled trial to investigate whether the use of this technique impacts the accuracy of CVC placement., Methods: Patients in group ECG (n = 147) had a CVC placed using right-atrial ECG to guide catheter tip positioning. CVCs in group NO-ECG (n = 143) were positioned without this technique., Results: Overall, guidewire-ECG control resulted in more correctly positioned CVCs (96% vs 76%, P < or = 0.001) without increasing placement time. Significantly more CVCs were placed in the middle of the superior vena cava in group ECG (P < or = 0.001), although placement into the right atrium or right ventricle and into other vessels occurred significantly more often in group NO-ECG (P < or = 0.001). Twenty patients in group NO-ECG required repositioning of their CVC after surgery, whereas this maneuver was necessary only in three patients in group ECG (P < or = 0.001)., Conclusions: ECG guidance allows for more accurate CVC placement, and should be considered to increase patient safety and reduce costs associated with repositioning procedures.