Diurnal rythm of Nampt is gender and weight dependent.

RESEARCH AIM: Nicotinamide phosphoribosyltransferase (Nampt) is an adipocytokine that is elevated in obesity, type 2 diabetes and increased levels are associated with inflammatory processes. Nampt serum concentrations have been suggested to follow a diurnal rhythm peaking in the afternoon in lean males. However, no data exists regarding the effects of gender and body weight. MATERIAL AND METHODS: We measured Nampt serum levels over 24 h in a cohort of healthy individuals living with either normal weight or obesity. Furthermore, effects of meals, oral glucose tolerance test and physical exercise on Nampt concentrations were evaluated. Correlation analyses to other hormonal- and lab parameters and anthropometric measurements were performed. RESULTS: Nampt showed a diurnal rhythm with increased levels at daytime and a peak in the early afternoon. This diurnal rhythm was significant for all groups but obese males. The Nampt amplitude, measured both relatively and absolutely, was significantly higher in females than in males. Meals did not influence Nampt serum levels, whereas physical exercise and an OGTT did significantly influence Nampt serum levels. CONCLUSION: In conclusion, we found gender specific differences in Nampt amplitude and coefficient variation with both being higher in females. The circadian rhythm of Nampt was independent of gender in healthy lean individuals, whereas it was disturbed in men with obesity.

Varying ENT practices in adult post-intubation laryngotracheal stenosis after the COVID epidemic in France: A CHERRIES analysis.

AIM: The SARS-CoV-2 pandemic may increase the incidence of iatrogenic laryngotracheal stenosis (LTS), whereas management is not well defined. The aim of this study was to survey a panel of French otorhinolaryngologists about their practices and to evaluate their needs. METHOD: A national-level survey of the management of iatrogenic LTS was conducted using a 41-item questionnaire, in 4 sections, sent to a panel of French otorhinolaryngologists between July and December 2022. The main endpoint was heterogeneity in responses between 55 proposals on LTS management. RESULTS: The response rate was 20% (52/263). The response heterogeneity rate was 69% (38/55). Heterogeneity concerned general questions on diagnosis (7/12, 58%) and management (7/10, 70%), LTS case management (22/27, 81%), and otorhinolaryngologists' expectations (33%, 2/6). Quality of training was considered good or excellent by only 21% of respondents. More than 80% were strongly in favor of creating national guidelines, expert centers and a national database. DISCUSSION: This study demonstrated the heterogeneity of adult post-intubation LTS management between otorhinolaryngologists in France. Training quality was deemed poor or mediocre by a majority of respondents. They were in favor of creating national guidelines and expert centers in LTS.

[Hereditary hemorrhagic telangiectasia]. / La maladie de Rendu-Osler (télangiectasie hémorragique héréditaire).

Hereditary hemorrhagic telangiectasia, also known as Rendu-Osler - Weber disease, is a rare, autosomal dominant vascular disease, with prevalence of 1/5,000. The condition is characterized by muco-cutaneous telangiectasias, which are responsible for a hemorrhagic syndrome of variable severity, as well as arteriovenous malformations (AVMs) appearing in the lungs, the liver, and the nervous system. They can be the source of shunts, which may be associated with high morbidity (neurological ischemic stroke, brain abscess, high-output heart failure, biliary ischemia…). It is therefore crucial to establish a clinical diagnosis using the Curaçao criteria or molecular diagnosis based on genetic analysis of the ENG, ACVRL1, SMAD4 and GDF2 genes. In most cases, multidisciplinary management allows patients to have normal life expectancy. Advances in interventional radiology and better understanding of the pathophysiology of angiogenesis have resulted in improved therapeutic management. Anti-angiogenic treatments, such as bevacizumab (BVZ, an anti-VEGF antibody), have proven to be effective in cases involving bleeding complications and severe liver damage with cardiac repercussions. Other anti-angiogenic agents are currently being investigated, including tyrosine kinase inhibitors.

A critical evaluation of the EU-virtual consultation platform (CPMS) within the European Reference Network on Rare Endocrine Conditions.

In 2017, the European Commission installed 24 European Reference Networks (ERNs) for different categories of rare and complex conditions to facilitate cross-border health care via virtual case consultations in a secure Clinical Patient Management System (CPMS). The ERN for rare endocrine conditions (Endo-ERN) previously reviewed the CPMS, in which they detailed the difficulties physicians encountered with the system and proposed solutions to these that should enable the system to be used to a greater extent. This paper will further the endeavor of the first by performing a critical evaluation of the CPMS, assessing how these suggested improvements have been implemented, and if these have affected the usage of the system. The evaluation involves an assessment of CPMS usage statistics since its conception that takes into consideration the technical updates and the external factors that may have affected these, including data from a review survey following a training workshop for our new healthcare providers (HCPs) added in January 2022. It appears that the improvements made to the system since the first review, in particular the implementation of the Operational Helpdesk, have had a positive effect in increasing CPMS membership; however, the regular usage of the system continues to fluctuate. Several suggestions are made on how to further facilitate the use of CPMS by our members both individually and network-wide, by integrating CPMS activities with other network initiatives and further integrating these into national health care systems as well as looking for ways to measure patient satisfaction from the CPMS discussions outcomes.

Durable memories and efficient neural coding through mnemonic training using the method of loci.

Mnemonic techniques, such as the method of loci, can powerfully boost memory. We compared memory athletes ranked among the world's top 50 in memory sports to mnemonics-naïve controls. In a second study, participants completed a 6-week memory training, working memory training, or no intervention. Behaviorally, memory training enhanced durable, longer-lasting memories. Functional magnetic resonance imaging during encoding and recognition revealed task-based activation decreases in lateral prefrontal, as well as in parahippocampal and retrosplenial cortices in both memory athletes and participants after memory training, partly associated with better performance after 4 months. This was complemented by hippocampal-neocortical coupling during consolidation, which was stronger the more durable memories participants formed. Our findings advance knowledge on how mnemonic training boosts durable memory formation through decreased task-based activation and increased consolidation thereafter. This is in line with conceptual accounts of neural efficiency and highlights a complex interplay of neural processes critical for extraordinary memory.

Does advanced age affect treatment of early glottic carcinoma?

AIMS: Early glottic carcinoma is currently managed by radiation therapy or endoscopic surgery. Both are effective in elderly patients, but their respective indications are poorly determined. The present study assessed our management of very elderly patients with early glottic carcinoma. MATERIAL AND METHODS: A retrospective single-center study included all patients aged 75 years and older at diagnosis, treated by radiation therapy or endoscopic surgery with curative intent for T1 or T2 glottic carcinoma between 2004 and 2018. RESULTS: Records of 33 patients (27 men and 6 women; mean age, 82.2 years (range, 76.1-93.1 years)) were reviewed. 24 patients received radiation therapy and 9 endoscopic resection. The only factor for choice of treatment was anterior commissure involvement. Overall survival was 87% at 2 years and 62% at 5 years. 19% of patients relapsed within 5 years and had to undergo further treatment. There were no treatment-related deaths. Radiation therapy was associated with more acute local complications, with two temporary treatment interruptions and one uncompleted treatment. Surgical treatment was more likely to result in dysphonia, found in 80% of cases. CONCLUSION: Treatment of early glottic cancer in elderly subjects can consist in either radiotherapy or endoscopic surgery. Age should not affect management. Surgical treatment is shorter and better tolerated, although with poorer vocal outcome, and may be preferred in the most comorbid patients.

Adipocytokines may delay pubertal maturation of human Sertoli cells.

Reproduction is an important target of obesity complications, including adverse effects on spermatogenesis and steroidogenesis. Adipocytokines are key mediators in various complications of obesity. Our aim was to study the potential of adipocytokines to affect Sertoli cell function, which is crucial for spermatogenesis, and possibly link these findings to the observed attenuation of spermatogenesis in obese males. Testicular biopsies were obtained from healthy donors. Highly purified adult human Sertoli cells (HSCs) were isolated by fluorescence-activated cell sorting. Cells were cultured and exposed to different concentrations of adipocytokines (10-1000ngmL-1 ) for 2-7 days. Expression of selected Sertoli cell genes was quantified by quantitative polymerase chain reaction. Long-term treatment (7 days) of HSCs with higher concentrations of chemerin, irisin, nicotinamide phosphoribosyltransferase (Nampt), resistin and progranulin significantly suppressed FSH receptor expression (by 79%, 83%, 64%, 71% and 26% respectively; P P invitro , may negatively affect Sertoli cell maturation and retain these cells in a more prepubertal stage. This could negatively affect testis function and add to fertility problems in obese adults.

Normal and resonant Auger spectroscopy of isocyanic acid, HNCO.

In this paper, we investigate HNCO by resonant and nonresonant Auger electron spectroscopy at the K-edges of carbon, nitrogen, and oxygen, employing soft X-ray synchrotron radiation. In comparison with the isosteric but linear CO2 molecule, spectra of the bent HNCO molecule are similar but more complex due to its reduced symmetry, wherein the degeneracy of the π-orbitals is lifted. Resonant Auger electron spectra are presented at different photon energies over the first core-excited 1s → 10a' resonance. All Auger electron spectra are assigned based on ab initio configuration interaction computations combined with the one-center approximation for Auger intensities and moment theory to consider vibrational motion. The calculated spectra were scaled by a newly introduced energy scaling factor, and generally, good agreement is found between experiment and theory for normal as well as resonant Auger electron spectra. A comparison of resonant Auger spectra with nonresonant Auger structures shows a slight broadening as well as a shift of the former spectra between -8 and -9 eV due to the spectating electron. Since HNCO is a small molecule and contains the four most abundant atoms of organic molecules, the reported Auger electron decay spectra will provide a benchmark for further theoretical approaches in the computation of core electron spectra.

Sequential Sedimentation-Biofiltration System for the purification of a small urban river (the Sokolowka, Lodz) supplied by stormwater.

The study analyses the efficiency of a Sequentional Sedimentation-Biofiltration System (SSBS) built on the Sokolowka river in Lodz (Poland). It was constructed to purify a small urban river whose hydrological regime is dominated by stormwater and meltwater. The SSBS was constructed on a limited area as multi-zone constructed wetlands. The SSBS consists of three zones: sedimentation zone with structures added to improve sedimentation, a geochemical barrier made of limestone deposit and biofiltration zone. The purification processes of total suspended solids (TSS), total phosphorus (TP), total nitrogen (TP) and other nutrients: phosphates (PO43-), ammonium (NH4+) and nitrates (NO3-) of the SSBS were analyzed. Chloride (Cl-) reduction was investigated. Monitoring conducted in the first two hydrological years after construction indicated that the SSBS removed 61.4% of TSS, 37.3% of TP, 30.4% of PO43-, 46.1% of TN, 2.8% of NH4+, 44.8% of NO3- and 64.0% of Cl-. The sedimentation zone played a key role in removing TSS and nutrients. The geochemical barrier and biofiltration zone each significantly improved overall efficiency by 4-10% for TSS, PO43-, TN, NO3- and Cl-. Although the system reduced the concentration of chloride, further studies are needed to determine the circulation of Cl- in constructed wetlands (CWs), and to assess its impact on purification processes.

Preliminary evaluation of cytosine-phosphate-guanine oligodeoxynucleotides bound to gelatine nanoparticles as immunotherapy for canine atopic dermatitis.

Cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN) are a promising new immunotherapeutic treatment option for canine atopic dermatitis (AD). The aim of this uncontrolled pilot study was to evaluate clinical and immunological effects of gelatine nanoparticle (GNP)-bound CpG ODN (CpG GNP) on atopic dogs. Eighteen dogs with AD were treated for 8 weeks (group 1, n=8) or 18 weeks (group 2, n=10). Before inclusion and after 2 weeks, 4 weeks, 6 weeks (group 1+2), 8 weeks, 12 weeks and 16 weeks (group 2) 75 µg CpG ODN/dog (bound to 1.5 mg GNP) were injected subcutaneously. Pruritus was evaluated daily by the owner. Lesions were evaluated and serum concentrations and mRNA expressions of interferon-γ, tumour necrosis factor-α, transforming growth factor-ß, interleukin (IL) 10 and IL-4 (only mRNA expression) were determined at inclusion and after 8 weeks (group 1+2) and 18 weeks (group 2). Lesions and pruritus improved significantly from baseline to week 8. Mean improvements from baseline to week 18 were 23 per cent and 44 per cent for lesions and pruritus, respectively, an improvement of ≥50 per cent was seen in six out of nine and three out of six dogs, respectively. IL-4 mRNA expression decreased significantly. The results of this study show a clinical improvement of canine AD with CpG GNP comparable to allergen immunotherapy. Controlled studies are needed to confirm these findings.

Cancer Risk after Fat Transfer: A Multicenter Case-Cohort Study.

BACKGROUND: Fat transfer is an increasingly popular method for refining postmastectomy breast reconstructions. However, concern persists that fat transfer may promote disease recurrence. Adipocytes are derived from adipose-derived stem cells and express adipocytokines that can facilitate active breast cancer cells in laboratory models. The authors sought to evaluate the association between fat transfer to the reconstructed breast and cancer recurrence in patients diagnosed with local or regional invasive breast cancers. METHODS: A multicenter, case-cohort study was performed. Eligible patients from four centers (Memorial Sloan Kettering, M. D. Anderson Cancer Center, Alvin J. Siteman Cancer Center, and the University of Chicago) were identified by each site's institutional tumor registry or cancer data warehouse. Eligibility criteria were as follows: mastectomy with immediate breast reconstruction between 2006 and 2011, age older than 21 years, female sex, and incident diagnosis of invasive ductal carcinoma (stage I, II, or III). Cases consisted of all recurrences during the study period, and controls consisted of a 30 percent random sample of the study population. Cox proportional hazards regression was used to evaluate for association between fat transfer and time to recurrence in bivariate and multivariate models. RESULTS: The time to disease recurrence unadjusted hazard ratio for fat transfer was 0.99 (95 percent CI, 0.56 to 1.7). After adjustment for age, body mass index, stage, HER2/Neu receptor status, and estrogen receptor status, the hazard ratio was 0.97 (95 percent CI, 0.54 to 1.8). CONCLUSION: In this population of breast cancer patients who had mastectomy with immediate reconstruction, fat transfer was not associated with a higher risk of cancer recurrence. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Prepubertal onset of obesity negatively impacts on testicular steroidogenesis in rats.

Obesity is a global health problem and impacts negatively on levels of testosterone and quality of sperm production. At present little is known about mechanisms that attenuate testicular function in obese males. Our study characterized testicular steroidogenesis and explored levels of relevant paracrine and hormonal factors in rats with short- and long-term obesity. We have found that obesity state increased serum levels of estradiol and leptin in both groups of obese rats and inhibited the expression of StAR and Cyp11a1 associated with low levels of intratesticular testosterone in rats with long-term obesity. Further, long-term obesity reduced the number of Leydig cells, increased the testicular levels of the proinflammatory adipocytokine TNFα and the number of testicular macrophages. All together, our data indicate that long-term obesity may cause chronic inflammation in the testis and negatively impacts on Leydig cell steroidogenesis.

Insulin-Like Peptide 5 Interacts with Sex Hormones and Metabolic Parameters in a Gender and Adiposity Dependent Manner in Humans.

Insulin-like peptide 5 (INSL5) is a gut hormone produced by L-cells in the colorectal epithelium and may play a role in the regulation of metabolic processes. The biological role of INSL5 is poorly investigated and nothing is known about the role of this hormone in obese and lean humans. Two cohorts were analyzed in the study. In the first cohort (n=76) the relationship between serum levels of INSL5 and different metabolic and hormonal parameters in obese and lean men and women were investigated. In the second cohort 14 male subjects underwent bariatric surgery. Circulating levels of INSL5 were then measured before and after interventions.We report for the first time that circulating INSL5 interacts with multiple metabolic and hormonal variables in lean and obese men and women and is affected by bariatric surgery. Serum levels of INSL5 negatively correlated with testosterone and blood lipids but positively with cortisol in obese men. In contrast to males, obese women had a strong negative correlation of plasma levels of INSL5 with C-reactive protein (CRP). We observed that adipose tissue loss after bariatric surgery significantly reduced serum levels of INSL5 in obese men with and without Type 2 Diabetes Mellitus (T2DM) that was associated with the restoration of circulating levels of testosterone. All together, our data demonstrated that INSL5 may interact with some metabolic parameters in obese humans and this process is dependent of gender and obesity state.

Comparison of radial forearm flap and thoracodorsal artery perforator flap donor site morbidity for reconstruction of oral and oropharyngeal defects in head and neck cancer.

INTRODUCTION: Reconstruction of the oral cavity and oropharynx after tumour resection often involves the use of free flaps, but donor site morbidity must be taken into account. The radial forearm flap, the flap most commonly used in this setting, leaves a readily visible scar on an exposed region of the body. The thoracodorsal artery perforator flap (TDAP), which possesses the same plastic qualities as the radial forearm flap, leaves a scar that is hidden in the axilla. The purpose of this study was to evaluate the cosmetic results of radial forearm and thoracodorsal artery perforator free flap donor sites. MATERIAL AND METHODS: The medical charts of all patients undergoing reconstruction by a radial forearm or thoracodorsal artery perforator free flap between January 2011 and December 2011 were retrospectively reviewed. The Patient and Observer Scar Assessment Scales and the Vancouver Scar Scale were used to evaluate the quality of the scars. RESULTS: Reconstruction was performed by radial forearm flap in 4 cases and TDAP flap in 7 cases. The PSAS score was significantly lower in the TDAP group than in the radial forearm group (P=0.03), and the OSAS score was higher in the radial forearm group (21.5 versus 14). The Vancouver Scar Scale was significantly higher for radial forearm flap scars than for TDAP scars (8 versus 2.7, P=0.005). CONCLUSION: This is the first study to compare radial forearm and thoracodorsal artery perforator free flap donor site scars. It demonstrates the minimal TDAP donor site morbidity and the high level of patient satisfaction.

Principles of nerve repair in complex wounds of the upper extremity.

Peripheral nerve injuries are common in the setting of complex upper extremity trauma. Early identification of nerve injuries and intervention is critical for maximizing return of function. In this review, the principles of nerve injury, patient evaluation, and surgical management are discussed. An evidence-based approach to nerve reconstruction is reviewed, including the benefits and limitations of direct repair and nerve gap reconstruction with the use of autografts, processed nerve allografts, and conduits. Further, the principles and indications of commonly used nerve transfers in proximal nerve injuries are also addressed.

Extranodal lymphoma of the head and neck: a 67-case series.

UNLABELLED: The present study sought to describe clinical presentation in extranodal lymphoma of the head and neck (ELHN), with the aim of improving diagnostic management. MATERIAL AND METHODS: A single-center retrospective observational study was conducted over the period 2001-13. Age, gender, histologic type, location, type of clinical presentation, time interval between symptom onset and histologic diagnosis and presence of specific symptoms were recorded, as were the specialty of the physician initially consulted and of the physician taking the diagnostic sample. RESULTS: Sixty-seven cases of ELHN were diagnosed: 39 male and 28 female patients, with a median age of 68 years. B-cell lymphoma (84%) was more frequent than plasmacytoma (7%) or T-cell lymphoma (6%). Location was mainly palatine tonsil (28%), nasal fossa and sinus (19%), nasopharynx (14%) or parotid (13%). Revelation often involved a mass (33%), and only rarely any specific symptoms (9%). Time interval from symptom onset to diagnosis was short in aggressive lymphoma and longer in low-grade lymphoma (mean 4 and 10 months respectively). The physician initially consulted was an ENT specialist in 67% of cases, and an ENT specialist performed diagnostic sampling in 97% of cases. CONCLUSION: ELHN is a rare pathology (5 cases per year in our department) of highly variable clinical presentation depending on location and histologic type. The ENT physician should be prepared for diagnosis regardless of anatomic location, so as to optimize diagnostic management.

The microbiotest battery as an important component in the assessment of snowmelt toxicity in urban watercourses--preliminary studies.

The aim of the study was to use a battery of biotests composed of producers (Selenastrum capricornutum, Sorghum saccharatum, Lepidium sativum, and Sinapis alba), consumers (Thamnocephalus platyurus), and decomposers (Tetrahymena thermophila) to evaluate the toxicity of snowmelt and winter storm water samples. The toxicity of the samples collected in the winter period December to February (2010-2011), in one of the largest agglomerations in Poland, the city of Lodz, was compared to that of storm water samples taken under similar conditions in June. The most toxic snowmelt samples were found to be high acute hazard (class IV), while the remaining samples were rated as slight acute hazard (class II). L. sativum (in the Phytotox test) was the most sensitive test organism, giving 27 % of all toxic responses, followed by S. capricornutum with 23 % of all responses. T. thermophila was the least sensitive, with only 2 % of all toxic responses. The greatest range of toxicity was demonstrated by samples from the single family house catchment: no acute hazard (class I) to high acute hazard (class IV).

An electronic oral health record to document, plan and educate.

The University of British Columbia (UBC) in collaboration with a software developer (Planmeca Oy, Finland) created an electronic oral health record based on the principles of cognitive ergonomics rooted in the European research and development project 'ORQUEST' to guide students through medical, dental, social histories, examinations, treatment planning and progress notes. Clinicians in each dental specialty of the Faculty of Dentistry and software engineers cooperated to define the clinical content and workflow of clinical procedures in three phases: (i) development of a radiographic module, (ii) development of medical, dental, social and family histories, intra- and extra-oral examinations, progress notes and treatment planning and (iii) development of the orthodontic section accompanied by an optimisation phase to correct technical problems and clinical content issues. From a practical perspective, this EOHR enhances the clinical performance of students and the quality assurance capacity of the institution. It facilitates audits of clinical productivity and research, and it can be modified with relative ease to suit similar educational and clinical environments in either public or private healthcare settings.

Velopharyngeal function after free thoracodorsal artery perforator flap in lateral and superior oropharyngeal cancer.

The purpose of this study was to report our experience with the free thoracodorsal artery perforator flap for reconstruction of the oropharynx and soft palate in head and neck cancer using a retrospective review of the medical charts of all patients undergoing oropharyngeal reconstruction by free thoracodorsal artery perforator flap during the same procedure as cancer resection between January 2011 and April 2013. Evaluation of speech, feeding and the presence of nasal emissions was performed 6 months after treatment in accordance with the Declaration of Helsinki. Nine patients were evaluated. Clear understanding of the patient was reported by the family and the examiner for seven patients, while understanding difficulties were reported for two patients (1 case of flap dehiscence and 1 technical error of flap fixation). The results indicated that, due to its complex anatomy and function, reconstruction of the soft palate remains a delicate procedure. The free thoracodorsal artery perforator flap allows functional soft palate reconstruction, while limiting donor site morbidity.