Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Selected amino acids, dipeptides and arylalkylamine derivatives do not act as allosteric modulators at GABAB receptors.

Based on recent reports describing enhancing actions of arylalkylamines (fendiline [N-(3,3-diphenylpropyl)-alpha-methylbenzylamine] and prenylamine [N-(3,3-diphenylpropyl)-alpha-methylphenethylamine]), amino acids (L-phenylalanine, L-leucine and L-isoleucine), and dipeptides (L-Phe-Phe and L-Phe-Leu) on baclofen-induced responses in cortical slices, we have examined whether these compounds might act as positive allosteric modulators at GABA(B) receptors. Unlike the previously described allosteric GABA(B) receptor modulator CGP7930 (2,6-Di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol), these compounds did not enhance GABA(B) receptor-mediated guanosine 5'-O-(3-thiotriphosphate) [GTP(gamma)35S] binding in native or recombinant cell membrane preparations. Similarly, in a competition binding assay using the antagonist radioligand [3H]CGP62349, CGP7930, but not the other compounds, enhanced the affinities of gamma-aminobutyric acid (GABA) for native GABA(B) receptors from rat brain cortex. Finally, in a cellular assay (Ca(2+) signaling in a recombinant cell line), CGP7930 was again the only compound found to enhance the GABA response. It is concluded that the arylalkylamines, amino acids and dipeptides tested do not act as allosteric modulators at native and recombinant GABA(B) receptors

Mucosal immune environment in colonic carcinogenesis: CD80 up-regulation in colonic dysplasia in ulcerative colitis

Abstract: Background: In patients with ulcerative colitis (UC) the inconsistency between the rate of dysplasia and actual cancer incidence suggests the presence of an immunosurveillance mechanism. The aim of our study was to analyse the expression of CD80 and CD86 during the different stages of UC-associated and in non-inflammatory carcinogenesis. Patients and methods: Sixty-two patients affected with UC, UC with colonic dysplasia, UC and cancer, colonic adenoma, or colonic cancer and 11 healthy subjects were enroled in our study. Tissue samples were taken from surgical specimens during colonic resection or during colonoscopy. Mucosal mRNA expression of CD80 and CD86 was quantified with real time polymerase chain reaction (RT-PCR). CD80, CD86 and p53 expressions and lamina propria mononuclear cell populations (CD3, CD20 and CD68) were analysed by immunohistochemistry. Mucosal levels of IL-1 beta, IL-2 and IFN-gamma were measured with immunometric assays. Results: Among UC patients, CD80 protein expression was higher in those with dysplasia (p = 0.017). In non-inflammatory carcinogenesis pathway CD80 protein and mRNA expressions were lower compared to the corresponding steps in the UC pathway. CD80 expression was directly correlated with the lamina propria mononuclear cell populations (T and B lymphocytes and monocytes). CD80 protein, but not CD80 mRNA, expression was significantly and directly correlated with IL-2 expression. Conclusion: CD80 resulted to be up-regulated in UC with dysplasia, while it was down-regulated in cancer. CD80 mucosal levels correlate with lamina propria T-cell and with IL-2 expression suggesting that it may elicit an active role in the immunosurveillance mechanis

Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity. Science 304:1021–1024

Activation of N-methyl-D-aspartate subtype glutamate receptors (NMDARs) is required for long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic transmission at hippocampal CA1 synapses, the proposed cellular substrates of learning and memory. However, little is known about how activation of NMDARs leads to these two opposing forms of synaptic plasticity. Using hippocampal slice preparations, we showed that selectively blocking NMDARs that contain the NR2B subunit abolishes the induction of LTD but not LTP. In contrast, preferential inhibition of NR2A-containing NMDARs prevents the induction of LTP without affecting LTD production. These results demonstrate that distinct NMDAR subunits are critical factors that determine the polarity of synaptic plasticity. The molecular mechanisms underlying activity-dependent modification of synaptic strength have been under intensive investigation because of their fundamental importance in brain function and dysfunction (1, 2). Homosynaptic long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission mediated by ␣-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid subtype glutamate receptors (AMPARs) at Schaffer collateral-CA1 synapses of the hippocampus are by far the best-characterized cellular models of synaptic plasticity. Both LTP and LTD require N-methyl-D-aspartate subtype glutamate receptor (NMDAR) activation (1, 3). However, the detailed mechanisms by which the activation of the same class of receptor can produce two opposing forms of synaptic modification remain unclear. A long-held belief has been that the degree of NMDAR activation, and hence the level of postsynaptic calcium elevation during the induction period, dictates the direction of NMDAR-dependent synaptic modification. The strongest evidence for this hypothesis comes from the conversion of LTP to LTD by a partial blockade of NMDARs with low concentrations of the NMDAR antagonist D,L-2-amino-5-phosphophonovaleric acid (APV) (4, 5 ). NMDARs are assembled from NMDAR subunit 1 (NR1) and at least one type of NR2 subunit (6). In the adult rat hippocampus, NR2A and NR2B are the predominant NR2 subunits We first investigated the effect of blocking NR2B-containing NMDARs on LTP and LTD of CA1 field excitatory postsynaptic potentials (fEPSPs) induced by high-and low-frequency stimulation (HFS and LFS), respectively (15). The NR2B subunitselective antagonist ifenprodil (3 M) (16) completely abolished the induction of LTD by LFS, suggesting that LTD requires the activation of NR2B-containing NMDARs It is unlikely that the selective blockade of LTD by NR2B-specific antagonists is due merely to a partial inhibition of NMDARs, because LTP rather than LTD is more sensitive to the partial NMDAR blockade produced by low concentrations of APV (4, 5). To rule out such a possibility, we tested the effect of low-dose APV that generated a partial blockade of NMDAR-mediated excitatory postsynaptic currents (EPSCs) similar to that produced by NR2B antagonist

INFLUENCE OF PHYSIOLOGICAL DIETARY SELENIUM SUPPLEMENTATION ON THE NATURAL COURSEOF AUTOIMMUNE THYROIDITIS

Our study aimed to investigate whether physiological doses of selenium (Se) influence the natural course of autoimmune thyroiditis (AIT). DESIGN AND PATIENTS: A total of 76 consecutive patients (65 F, 11 M, median 43, range 15-75 years) with AIT, normal or slightly elevated TSH and fT4 within the normal range were divided into two groups: Group 0 (30 cases) was given no treatment while Group 1 (46 cases) was treated with sodium selenite 80 \u3bcg/day as a single oral dose for 12 months. Thyroperoxidase and thyroglobulin autoantibodies (TPO-Ab; Tg-Ab), TSH, fT4 and urine iodine concentrations (UIC) were measured at baseline and after 6 and 12 months of follow-up. Thyroid ultrasonography (US) was performed at each follow-up point. Echogenicity was measured by histographic analysis of gray-scale pixels (gsp) ranging from 0 = black to 255 = white. RESULTS: Thyroid echogenicity decreased significantly in both groups after 6 months, but after 12 months, it had changed no more in Group 1, whereas it had dropped further in Group 0. No significant variation in TPO-Ab or Tg-Ab levels was observed between the two groups after 6 months, but both values decreased significantly after 12 months in Group 1, and five patients in this group became negative for TPO-Ab. TSH and FT4 showed no significant variations in either group. CONCLUSIONS: Dietary supplementation with physiological doses of Se seems to be effective in preventing a reduction in thyroid echogenicity after 6 months of treatment and in reducing TPO-Ab and Tg-Ab after 12 months, but does not modify TSH or FT4

Cytokine Network in Rectal Mucosa in Perianal Crohn's Disease: Relations with Inflammatory Parameters and Need for Surgery

Abstract BACKGROUND: Nowadays anti-TNF-alpha antibodies are used for the treatment of perianal Crohn's disease (CD). Nevertheless, this treatment is effective in only a part of these patients and recent studies suggested a role for other cytokines in chronic bowel inflammation. The aim of this study was to assess the cytokine profile in the rectal mucosa of patients affected by perianal CD and to understand its relations with the systemic cytokine profile and inflammatory parameters and the need for surgery. METHODS: Seventeen patients affected by perianal CD, 7 affected by CD without perianal involvement, and 17 healthy controls were enrolled and underwent blood sampling and endoscopy. During endoscopy rectal mucosal samples were taken and the expression of TNF-alpha, IL-6, IL-1 beta, IL-12, and TGF-beta1 was quantified with enzyme-linked immunosorbent assay (ELISA). Local cytokine levels were compared and correlated with diagnosis, therapy, phenotype (fistulizing and stenosing), and disease activity parameters. RESULTS: In the group with perianal CD, rectal mucosal IL-1 beta, IL-6, and serum IL-6 and TNF-alpha were higher than in patients with small bowel CD and healthy controls. IL-12 and TGF-beta1 mucosal levels did not show any differences among the 3 groups. Mucosal IL-6 significantly correlated with the Perianal Crohn's Disease Activity Index and mucosal TNF-alpha and IL-1 beta. Mucosal TNF-alpha and IL-1 beta showed a direct correlation with the histological grade of disease activity. CONCLUSIONS: The cytokines network analysis in perianal CD shows the important involvement of IL-1 beta, IL-6, and TNF-alpha. Furthermore, mucosal levels of IL-6 and IL-12 are predictors of recurrence and of need for surgery in perianal CD patients

Sentinel node biopy in breast cancer.

Axillary lymph node dissection (ALND) is an important tool in staging patients with breast cancer. However, this procedure has several sequelae and complications and improvement in early diagnosis has led to an increasing number of cases of ALND in which axillary nodes are found to be negative. Sentinel node (SN) biopsy appears to be a less invasive alternative to ALND. The aim of the present study was to assess whether SN is a reliable indicator for axillary staging. We studied 126 consecutive patients with T1-T2 breast cancer and clinically negative axilla. In each case, 30-70 MBq of 99mTC-labelled colloidal albumin was injected subdermally close to the tumour and SN was visualised by lymphoscintigraphy. Surgery was performed 24 h after injection and the SN was removed under the guidance of a gamma ray-detecting probe. ALND was then undertaken in all cases. A histopathologic examination of the SNs was then made and the findings compared with the status of the other axillary nodes. SNs were identified and biopsied in 115/126 patients (91.3%) and correctly predicted the axillary status in 110/115 cases (95.6%). In five cases (4.4%), SNs were found to be negative, but other axillary nodes were positive. Our data confirm that SN biopsy is a good method for staging the axilla in patients with breast cancer. However, before SN biopsy can replace ALND in daily clinical practice, some technical aspects must be standardized, and clinical trials are required in order to clarify the prognostic impact of false-negative cases