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STUDY QUESTION Is there an increase in the total number of metaphase II (MII) oocytes between a conventional ovarian stimulation (OS) and a double uninterrupted stimulation? SUMMARY ANSWER There is no increase in the total number of MII oocytes when comparing one conventional OS to a continuous stimulation with double oocyte aspiration. WHAT IS KNOWN ALREADY Based on the concept of multiple follicular waves, the combination of two stimulations in the same ovarian cycle has gained interest in patients with a low ovarian reserve. This so-called dual stimulation approach is usually characterized by a discontinuation of FSH administration for ∼5 days and appears to have a favourable impact on the number of retrieved oocytes without affecting the embryo quality or ploidy status. The outcomes of dual uninterrupted OS have not yet been studied. STUDY DESIGN, SIZE, DURATION This was an open-label randomized controlled trial (RCT) with superiority design, performed in a single tertiary centre. Subjects were randomized with a 1:1 allocation into two groups between October 2019 and September 2021. All patients underwent a conventional stimulation with recombinant FSH. When two or more follicles of 17 mm were present, the final inclusion criterion was assessed; randomization occurred only in the presence of ≤9 follicles of ≥11 mm. In Group A, ovulation was triggered with hCG, and oocyte retrieval (OR) was performed 34–36 h later, followed by a fresh single or double embryo transfer (SET or DET) on Day 3/5. In Group B, ovulation was triggered with GnRH agonist, followed by another OS, without discontinuation of the FSH administration. In the presence of one or more follicles of ≥17 mm, the second stimulation was completed with hCG. A freeze-all strategy (Day 3/5) was applied for both retrievals, followed by transfer of one or two embryos in an artificially prepared frozen-thawed cycle. In the absence of one or more follicles of ≥17 mm after 13 additional days of stimulation, the second cycle was cancelled. All ORs were executed by a senior fertility specialist who was blinded for the first treatment, and all follicles >10 mm were aspirated, according to routine clinical practice. The primary outcome was the total number of MII oocytes. Patients were followed up until all embryos were transferred, or until live birth was achieved. Other secondary outcomes included the number of cumulus–oocyte complexes (COCs), the number of good quality embryos (Day 3/5), the ongoing pregnancy rate, and gonadotropin consumption. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients between 25 and 40 years old, with an anti-Müllerian hormone level of ≤1.5 ng/ml, antral follicle count of ≤6, or ≤5 oocytes after a previous stimulation, were included. At the start, 70 patients were eligible for participation in the trial, of whom 48 patients fulfilled the final inclusion criterium and were randomized. After drop-out of two patients, 23 patients were randomized to a single round of OS (Group A), and 23 patients were randomized to two uninterrupted rounds of OS (Group B). MAIN RESULTS AND THE ROLE OF CHANCE Baseline characteristics were similar between both groups. The cumulative number of COCs and MII oocytes after completion of the second OR was similar in Group A and Group B [5.3 ± 2.7 versus 5.3 ± 3.0 (P  = 0.95); 4.1 ± 2.4 versus 4.3 ± 2.7 (P  = 0.77)]. Likewise, a comparable number of excellent and good quality embryos was available on Day 3 (3.0 ± 2.0 versus 2.7 ± 2.0; P  = 0.63). In Group B, the cancellation rate due to insufficient response to the second round of stimulation was 39.1% (9/23). When focusing on the first stimulation in both groups, there were no significant differences regarding basal FSH, gonadotropin consumption, and the number of preovulatory follicles. After the first OR, the mean number of COC and MII oocytes was significantly higher in Group A (who had hCG triggering), compared to Group B (who had GnRH agonist triggering) [5.3 ± 2.7 versus 3.3 ± 2.2; difference 95% CI (0.54 to 3.45), P  = 0.004 and 4.1 ± 2.4 versus 3.0 ± 2.2; difference 95% CI (−0.15 to 2.6), P  = 0.05, respectively]. Likewise, the number of excellent and good quality embryos on Day 3 was significantly higher (3.0 ± 2.0 versus 1.9 ± 1.7; P  = 0.02) in Group A. LIMITATIONS, REASONS FOR CAUTION This study was powered to demonstrate superiority for the number of MII oocytes after dual stimulation. Investigating the impact of dual stimulation on pregnancy rates would have required a larger sample size. Furthermore, the heterogeneity in embryo vitrification and transfer policies precluded a correct comparison of embryologic outcomes between both groups. WIDER IMPLICATIONS OF THE FINDINGS This is the first RCT investigating the role of continuous stimulation with double aspiration in low responders. Our results show no statistically significant differences in the cumulative number of MII oocytes between one conventional stimulation with fresh ET and two consecutive stimulations with a freeze-only approach. Furthermore, the observed suboptimal oocyte yield after agonist ovulation triggering in low responders in the dual uninterrupted OS group is a reason for concern and further scrutiny, given that previous RCTs have shown similar outcomes in normal and high responders after hCG and GnRH agonist triggers. STUDY FUNDING/COMPETING INTEREST(S) This work was supported in part by a research grant from Organon. H.T. received honoraria for lectures and presentations from Abbott, Cooper Surgical, Gedeon-Richter, Cook, Goodlife, and Ferring. L.B. received fees for lectures from Merck & Organon and support for attending ESHRE 2023. M.D.V. reports fees for lectures from Ferring, Merck, Organon, IBSA, Gedeon Richter, and Cooper Surgical and support for attending ASRM 2023. S.M. received honoraria for lectures and presentations from Abbott, Cooper Surgical, Gedeon-Richter, IBSA, and Merck. C.B. was on the Advisory board and received consulting fees from Theramex and received honoraria for lectures and presentations from Abbott, Ferring, Gedeon-Richter, IBSA, and Merck. TRIAL REGISTRATION NUMBER NCT03846544 TRIAL REGISTRATION DATE 19 February 2019 DATE OF FIRST PATIENT'S ENROLMENT 28 October 2019 [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the added value of enzymatic processing of testicular biopsies on testicular sperm retrieval (SR) rates for patients with non-obstructive azoospermia (NOA)? SUMMARY ANSWER In addition to mechanical mincing, enzymatic digestion increased SR rates in testicular biopsies of NOA patients. WHAT IS KNOWN ALREADY Many studies focus on the surgical approach to optimize recovery of testicular sperm in NOA, and in spite of that, controversy still exists about whether the type of surgery makes any difference as long as multiple biopsies are taken. Few studies, however, focus on the role of the IVF laboratory and the benefit of additional lab procedures, e.g. enzymatic digestion, in order to optimize SR rates. STUDY DESIGN, SIZE, DURATION This retrospective single-center cohort study included all patients who underwent their first testicular sperm extraction (TESE) by open multiple-biopsy method between January 2004 and July 2022. Only patients with a normal karyotype, absence of Y-q deletions and a diagnosis of NOA based on histology were included. The primary outcome was SR rate after mincing and/or enzymes. The secondary outcome was cumulative live birth (CLB) after ICSI with fresh TESE and subsequent ICSI cycles with frozen TESE. PARTICIPANTS/MATERIALS, SETTING, METHODS Multiple biopsies were obtained from the testis, unilaterally or bilaterally, on the day of oocyte retrieval. Upon mechanical mincing, biopsies were investigated for 30 min; when no or insufficient numbers of spermatozoa were observed, enzymatic treatment was performed using Collagenase type IV. Multivariable regression analysis was performed to predict CLB per TESE by adjusting for the following confounding factors: male FSH level, female age, and requirement of enzymatic digestion to find sperm. MAIN RESULTS AND THE ROLE OF CHANCE We included 118 patients, of whom 72 (61.0%) had successful SR eventually. Spermatozoa were retrieved after mechanical mincing for 28 patients (23.7%; 28/118) or after additional enzymatic digestion for another 44 patients (37.2%; 44/118). Thus, of the 90 patients requiring enzymatic digestion, sperm were retrieved for 44 (48.9%). Male characteristics were not different between patients with SR after mincing or enzymatic digestion, in regard to mean age (34.5 vs 34.5 years), testis volume (10.2 vs 10.6 ml), FSH (17.8 vs 16.9 IU/l), cryptorchidism (21.4 vs 34.1%), varicocele (3.6 vs 4.6%), or histological diagnosis (Sertoli-cell only 53.6 vs 47.7%, maturation arrest 21.4 vs 38.6%, sclerosis/atrophy 25.0 vs 13.6%). Of the 72 patients with sperm available for ICSI, 23/72 (31.9%) achieved a live birth (LB) after the injection with fresh testicular sperm (and fresh or frozen embryo transfers). Of the remaining 49 patients without LB, 34 (69.4%) had supernumerary testicular sperm frozen. Of these 34 patients, 19 (55.9%) continued ICSI with frozen testicular sperm, and 9/19 (47.4%) had achieved an LB after ICSI with frozen testicular sperm. Thus, the total CLB was 32/118 (27.1%) per TESE or 32/72 (44.4%) per TESE with sperm retrieved. Of the female characteristics (couples with sperm available), only female age (30.3 vs 32.7 years; P  = 0.042) was significantly lower in the group with a LB, compared to those without. The CLB with testicular sperm obtained after enzymatic digestion was 31.8% (14/44), while the CLB with sperm obtained after mincing alone was 64.3% (18/28). Multivariable logistic regression analysis showed that when enzymatic digestion was required, it was associated with a significant decrease in CLB per TESE (OR: 0.23 (0.08–0.7); P  = 0.01). LIMITATIONS, REASONS FOR CAUTION Limitations of the study are related to the retrospective design. However, the selection of only patients with NOA, and specific characteristics (normal karyotype and absence Y-q deletion) and having their first TESE, strengthens our findings. WIDER IMPLICATIONS OF THE FINDINGS Enzymatic processing increases the SR rate from testicular biopsies of NOA patients compared to mechanical mincing only, demonstrating the importance of an appropriate laboratory protocol. However, NOA patients should be counseled that when sperm have been found after enzymatic digestion, their chances to father a genetically own child may be lower compared to those not requiring enzymatic digestion. STUDY FUNDING/COMPETING INTEREST(S) None reported. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Background Promoter methylation of N-myc Downstream-Regulated Gene 4 ( NDRG4) in fecal DNA is an established early detection marker for colorectal cancer ( CRC). Despite its connection to CRC, NDRG4 is predominantly studied in brain and heart, with little to no knowledge about its expression or role in other organs. In this study, we aimed to determine the whole-body expression of NDRG4, with a focus on the intestinal tract. Methods We investigated NDRG4 expression throughout the body by immunohistochemistry, Western Blotting and in situ mRNA hybridization using tissues from NDRG4 wild-type, heterozygous and knockout mice and humans. In addition, we explored cell-specific expression of NDRG4 in murine whole-mount gut preparations using immunofluorescence and confocal microscopy. Key Results NDRG4 is specifically expressed within nervous system structures throughout the body. In the intestinal tract of both mouse and man, NDRG4 immunoreactivity was restricted to the enteric nervous system ( ENS), where it labeled cell bodies of the myenteric and submucosal plexuses and interconnecting nerve fibers. More precisely, NDRG4 expression was limited to neurons, as NDRG4 always co-localized with HuC/D (pan-neuronal marker) but never with GFAP (an enteric glial cell marker). Furthermore, NDRG4 was expressed in various neuropeptide Y positive neurons, but was only found in a minority (~10%) of neurons expressing neuronal nitric oxide synthase. Conclusions and Inferences NDRG4 is exclusively expressed by central, peripheral and enteric neurons/nerves, suggesting a neuronal-specific role of this protein. Our findings raise the question whether NDRG4, via the ENS, an understudied component of the tumor microenvironment, supports CRC development and/or progression. [ABSTRACT FROM AUTHOR]

Objective To investigate the impact of childhood trauma on the clinical course of panic disorder and possible contributing factors. Method Longitudinal data of 539 participants with a current panic disorder were collected from the Netherlands Study of Depression and Anxiety (NESDA). Childhood trauma was assessed with a structured interview and clinical course after 2 years with a DSM-IV-based diagnostic interview and the Life Chart Interview. Results At baseline, 54.5% reported childhood trauma, but this was not predictive of persistence of panic disorder. Emotional neglect and psychological abuse were associated with higher occurrence of anxiety disorders other than panic disorder (social phobia) and with higher chronicity of general anxiety symptoms (anxiety attacks or episodes and avoidance). Baseline clinical features (duration and severity of anxiety and depressive symptoms) and personality traits (neuroticism and extraversion) accounted for roughly 30-60% of the total effect of childhood trauma on chronicity of anxiety symptoms and on occurrence of other anxiety disorders. Conclusion After two years, childhood trauma is associated with chronicity of anxiety symptoms and occurrence of social phobia, rather than persistence of panic disorder. These relationships are partially accounted for by duration and severity of anxiety and depressive symptoms, and neuroticism and extraversion. [ABSTRACT FROM AUTHOR]

Dysphagia affects the most cardinal of human functions: the ability to eat and drink. The aim of this prospective study was to evaluate swallowing dysfunction in patients diagnosed with Zenker's diverticulum using the Swallowing Quality of Life (SWAL-QOL) questionnaire preoperatively. In addition, SWAL-QOL was used to assess changes in the outcome of swallowing function after endoscopic treatment of Zenker's diverticulum compared to baseline. Pre- and postoperative SWAL-QOL data were analyzed in 25 patients who underwent endoscopic treatment of Zenker's diverticulum between January 2011 and December 2013. Patients were treated by different endoscopic techniques, depending on the size of the diverticulum: CO2 laser technique or stapler technique, or the combination of both techniques used in larger diverticula. Their mean age was 69 years, and 28% of patients were female. The mean interval between endoscopic surgery and completion of the postoperative SWAL-QOL was 85 days. The median (min-max) preoperative total SWAL-QOL score was 621 (226-925) out of 1100, indicating the perception of oropharyngeal dysphagia and diminished quality of life. Following endoscopic treatment of Zenker's diverticulum, significant improvement was demonstrated in the postoperative total SWAL-QOL score of 865 (406-1072) out of 1100 (p < 0.001). On the majority of subscales of SWAL-QOL there was significant improvement between pre- and postoperative scores. To the authors' knowledge, this is the first report in the literature on the changes in pre- and postoperative SWAL-QOL scores for patients with Zenker's diverticulum before and after treatment. The results of this study indicate that endoscopic treatment of Zenker's diverticulum leads to significant symptom relief as documented by significant changes in the majority of the SWAL-QOL domains. [ABSTRACT FROM AUTHOR]

Accessible summary What is known on the subject? To stimulate reminiscence of older adults with dementia performed individually or through group sessions is a well-known practice in nursing homes resulting in effects on behaviour and well-being as an alternative for medication., Robust scientific proof of the effectiveness of individual reminiscence therapy performed in nursing homes is sparse., What this paper adds to existing knowledge? We have provided individual standardized reminiscence therapy to residents with dementia. The therapy was developed and tested in a previous study and performed in this study by trained nursing home volunteers., In comparison with a control group who received usual care, residents who received the reminiscence therapy showed significant less depressive symptoms. Moreover, residents were, in general, attentive, open and collaborative during the sessions and volunteers experienced the sessions as useful and pleasant., What are the implications for practice? Individual reminiscence therapy can be learned and used by nursing home volunteers to improve care in nursing homes., Abstract Aim To investigate the effect of a standardized individualized intervention based on the SolCos transformational reminiscence model on depressive symptoms (primary outcome), cognition and behaviour (secondary outcomes) for older people with mild to moderate dementia, performed by trained nursing home volunteers as facilitators. Background Because of limited pharmacological treatment options for older adults with dementia relevant physical, sensory, psychological or social interventions offer alternative opportunities. Method Randomized controlled trial (ISRCTN74355073) was set up in two nursing homes with 29 and 31 residents in the intervention and the control groups respectively. Eighteen nursing home volunteers were trained to perform the reminiscence therapy. Various assessment scales were measured pre- and post-sessions. Results Linear regression analysis showed an impact on depressive symptoms. However, no impact was identified on cognition and behaviour. Facilitators experienced the sessions as useful and pleasant, and study participants were, in general, attentive, open and collaborative. Discussion Study results showed that organizing standardized individual reminiscence therapy with nursing home volunteers was feasible and study participants' attention and participation were overall good. Further study initiatives to explore the potential of individual reminiscence therapy within a person-centred framework are recommended in order to improve care in nursing homes. [ABSTRACT FROM AUTHOR]

Objective: To compare the diagnostic value of cone-beam computed tomography (CBCT) and conventional radiography (CR) after acute small bone or joint trauma. Materials and methods: Between March 2013 and January 2014, 231 patients with recent small bone or joint trauma underwent CR and subsequent CBCT. CR and CBCT examinations were independently assessed by two readers, blinded to the result of the other modality. The total number of fractures as well as the number of complex fractures were compared, and inter- and intraobserver agreement for CBCT was calculated. In addition, radiation doses and evaluation times for both modalities were noted and statistically compared. Results: Fracture detection on CBCT increased by 35 % and 37 % for reader 1 and reader 2, respectively, and identification of complex fractures increased by 236 % and 185 %. Interobserver agreement for CBCT was almost perfect, as was intraobserver agreement for reader 1. The intraobserver agreement for reader 2 was substantial. Radiation doses and evaluation time were significantly higher for CBCT. Conclusion: CBCT detects significantly more small bone and joint fractures, in particular complex fractures, than CR. In the majority of cases, the clinical implication of the additionally detected fractures is limited, but in some patients (e.g., fracture-dislocations), the management is significantly influenced by these findings. As the radiation dose for CBCT substantially exceeds that of CR, we suggest adhering to CR as the first-line examination after small bone and joint trauma and keeping CBCT for patients with clinical-radiographic discordance or suspected complex fractures in need of further (preoperative) assessment. [ABSTRACT FROM AUTHOR]

Purpose: To study the treatment patterns, effectiveness and safety of zoledronic acid (ZOL) beyond 2 years of therapy, given the paucity of data on long-term treatment in daily clinical practice.Methods: Patients with multiple myeloma (MM) or solid tumor bone metastases (STM) and at least 24 months of regular q3-4w ZOL therapy were followed prospectively for an additional 18 months beyond the 24 months required for study entry. End-points included ZOL exposure, incidence of skeletal related events (SRE), and safety.Results: In all, 298 evaluable patients were enrolled. The mean continuation rate of ZOL was 90.6%. Exposure to ZOL decreased with time in all patients, but was lower (50.0% vs. 67.6%; p<0.001) and with higher discontinuation rates (incidence rate ratio [IRR]=1.95; p=0.002) in MM compared to the STM group. ZOL suppressed the rate of SREs similarly during the study as compared to before inclusion (0.12 vs. 0.13 events per person-year; p=0.7). At 18 months, 84.5% remained SRE-free. In STM patients, persistent ZOL therapy was associated with lower SRE risk (hazard ratio [HR]=0.42; p=0.01), but not in MM. Renal deterioration occurred in 3.7% and osteonecrosis of the jaw (ONJ) developed in 6.0%, with dental trauma increasing ONJ risk (HR=4.67; p=0.002).Conclusions: Beyond 2 years of therapy, treatment patterns of ZOL were heterogeneous and SRE rates were low. The safety profile of ZOL was acceptable, and interrupting ZOL in patients with solid tumors was associated with a higher risk of SREs. [ABSTRACT FROM AUTHOR]

Accessible summary Burnout and work engagement are two sides of one coin, two opposite poles related not only to how workers personally experience their jobs but also to how they experience their jobs within the context of work teams/groups., Engaged workers have a lot of energy, are very enthusiastic about their jobs and are absorbed by their work., Nurses' job performance in hospitals, including psychiatric hospitals, is dependent upon their relationships with physicians and other healthcare workers and their superiors, how they are involved in the decisions about their work and whether or not they are provided with the right resources and adequate support., When nursing teams are able to perform well, nurses tend to be more engaged and satisfied with their jobs and are more willing to stay in their positions., Engaged nursing teams report better quality of patient care in psychiatric hospitals., Abstract Research in healthcare settings reveals important links between work environment factors, burnout and organizational outcomes. Recently, research focuses on work engagement, the opposite (positive) pole from burnout. The current study investigated the relationship of nurse practice environment aspects and work engagement (vigour, dedication and absorption) to job outcomes and nurse-reported quality of care variables within teams using a multilevel design in psychiatric inpatient settings. Validated survey instruments were used in a cross-sectional design. Team-level analyses were performed with staff members ( n = 357) from 32 clinical units in two psychiatric hospitals in Belgium. Favourable nurse practice environment aspects were associated with work engagement dimensions, and in turn work engagement was associated with job satisfaction, intention to stay in the profession and favourable nurse-reported quality of care variables. The strongest multivariate models suggested that dedication predicted positive job outcomes whereas nurse management predicted perceptions of quality of care. In addition, reports of quality of care by the interdisciplinary team were predicted by dedication, absorption, nurse-physician relations and nurse management. The study findings suggest that differences in vigour, dedication and absorption across teams associated with practice environment characteristics impact nurse job satisfaction, intention to stay and perceptions of quality of care. [ABSTRACT FROM AUTHOR]

Purpose: Type D personality, defined as a combination of social inhibition and negative affectivity, has been associated with poor medication adherence and lower adherence to continuous positive airway pressure in patients with sleep-disordered breathing. Up to this date, the association of patient's personality with adherence with a mandibular advancement device (MAD) has not been studied. The purposes of this study were to examine the association between type D personality and poor adherence to MAD treatment and to examine the impact of type D personality on perceived side effects during this treatment. Methods: Eighty-two patients out of 113 patients with a known baseline type D scale who have started MAD treatment between June 2006 and December 2009 were included. Information about side effects and adherence were collected via a postal questionnaire. Thirty-three patients were using a monobloc MAD and 49 patients were using a duobloc MAD. Results: Forty-five percent of type D patients discontinued MAD treatment, whereas only 15 % of non-type D patients reported treatment discontinuation. The odds ratio for treatment discontinuation was 6.03 (95 % confidence interval 1.22-29.81; p = 0.027) for type D personality, adjusted for age, gender, MAD type (monobloc or duobloc), and decrease in apnea severity. In continuing MAD users, no significant difference in perceived side effects was reported between the personality types. Conclusion: This is the first study to examine the relationship between type D personality and adherence to MAD treatment. Type D patients reported a significantly higher discontinuation rate when compared to patients without type D personality. [ABSTRACT FROM AUTHOR]

Purpose: This prospective clinical study investigates the efficacy of a specific custom-made titratable mandibular advancement device (MAD) for the treatment of obstructive sleep apnea (OSA). This MAD has attachments in the frontal teeth area that allow for progressive titration of the mandible. Methods: Sixty-one adult OSA patients were included (age, 46.7 ± 9.0 years; male/female ratio, 45/16; apnea-hypopnea index (AHI), 23.2 ± 15.4 events/h sleep; body mass index, 27.9 ± 4.1 kg/m²). After an adaptation period, titration started based on a protocol of symptomatic benefit or upon reaching the physiological limits of protrusion. As a primary outcome, treatment response was defined as an objective reduction in AHI following MAD treatment of ≥50 % compared to baseline, and treatment success as a reduction in AHI with MAD to less than 5 and 10 events/h sleep. Compliance failure was defined as an inability to continue treatment. Results: A statistically significant decrease was observed in AHI, from 23.4 ± 15.7 at baseline to 8.9 ± 8.6 events/h with MAD ( p < 0.01). Treatment response was achieved in 42 out of 61 patients (68.8 %), whereas 42.6 % met criteria of AHI < 5 and 63.9 % achieved an AHI < 10 events/h sleep, respectively. Four patients (6.6 %) were considered as 'compliance failures.' Conclusions: The present study has evaluated the efficacy of a specific custom-made titratable MAD in terms of sleep apnea reduction. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Human adipose tissue macrophages (ATMs) display an alternatively activated (M2) phenotype, but are still able to produce excessive inflammatory mediators. However, the processes driving this particular ATM phenotype are not understood. Genome-wide association studies associated the CDKN2A locus, encoding the tumour suppressor p16, with the development of type 2 diabetes. In the present study, p16 levels in human ATMs and the role of p16 in acquiring the ATM phenotype were assessed. Methods: Gene expression of p16 in ATMs was analysed and compared with that in monocyte-derived macrophages (MDMs) from obese patients or with macrophages from human atherosclerotic plaques (AMs). Additionally, p16 levels were studied during macrophage differentiation and polarisation of monocytes isolated from healthy donors. The role of p16 in MDMs from healthy donors was investigated by small interfering (si)RNA-mediated silencing or adenovirus-mediated overproduction of p16. Results: Compared with MDMs and AMs, ATMs from obese patients expressed lower levels of p16. In vitro, IL-4-induced M2 polarisation resulted in lower p16 protein levels after differentiation of monocytes from healthy donors in macrophages. Silencing of p16 in MDMs mediated by siRNA increased the expression of M2 marker genes and enhanced the response to lipopolysaccharide (LPS), to give a phenotype resembling that of ATM. By contrast, adenovirus-mediated overproduction of p16 in MDMs diminished M2 marker gene expression and the response to LPS. Western blot analysis revealed that p16 overproduction inhibits LPS- and palmitate-induced Toll-like receptor 4 (TLR4)-nuclear factor of κ light polypeptide gene enhancer in B cells (NF-κB) signalling. Conclusions/interpretation: These results show that p16 inhibits the acquisition of the ATM phenotype. The age-related increase in p16 level may thus influence normal ATM function and contribute to type 2 diabetes risk. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess the necessity of post-marketing safety monitoring focused on osteonecrosis of the jaw (ONJ) in patients with bone metastatic cancer treated with denosumab (AMG162).Methods: The ONJ safety data from three randomized phase III trials were pooled, and risk ratios and power were computed using traditional methods and simulation.Results: A total of 89 ONJ cases (1.57%; 95% CI, 1.26-1.92) were reported with 52 (1.83%; 95% CI, 1.37-2.39) occurring in the denosumab group (n = 2,841) and 37 (1.30%; 95% CI, 0.92-1.79) in the zoledronic acid group (n = 2,836). Overall, the pooled risk ratio (RR) for ONJ was 1.40 (95% CI, 0.92-2.13; p = 0.11). In the trials reporting superior therapeutic efficacy of denosumab, the RR for ONJ was 1.61 (95% CI, 0.99-2.62; p = 0.052). However, neither separately nor pooled had any trial adequate power (>80%) to detect excess relative risks of ONJ of up to 76%, assuming fixed ONJ rates in the control arms. The joint power of the trials to detect the observed excess relative risk of 40% was only 36%. The rate of mucosal healing in patients with ONJ appeared similar in both groups (RR, 1.28; 95% CI, 0.66-2.45; p = 0.5).Conclusions: Although the overall frequency of ONJ was low, post-marketing risk-benefit studies with this novel compound appear warranted focusing specifically on this rare toxicity, which can potentially have a high impact on quality of life. [ABSTRACT FROM AUTHOR]

Contingency plans for hazards are based on scenarios at different scales. The most extreme scenarios reflect the idea of ‘think the unthinkable’. For large-scale floods in the Netherlands, this idea has been given an upper limit called ‘worst credible floods’: an upper limit for floods that are still considered realistic or credible by experts. Considering the enormous impact of a worst credible flood in the Netherlands and the uncertainty of how a disaster might unfold, a realistic preparation for flood disasters should leave room for improvisation and should be based on relatively simple plans, and on public awareness. The huge consequences of worst credible floods show that the country's safety will continue to depend on pro-active and preventive measures. [ABSTRACT FROM AUTHOR]

The objective of this study was to describe the prevalence of sexually transmitted infections (STI), sociodemographic and behavioural characteristics in a population of male sex workers (MSW) in Antwerp, Belgium. Between September 1999 and March 2004, 129 MSW were reached by Gh@pro, an outreach programme providing preventive health care, free STI check-up and hepatitis B vaccination, to sex workers (SW). Sera were collected from 121 men, urine samples from 115 men and a questionnaire was filled in by 43 MSW. In 45.5% of MSW one or more STI were diagnosed (including hepatitis B), 76% on laboratory testing at first screening, 9% through symptomatology at first visit. The prevalence of HIV was 10.8%, hepatitis B virus (HBV) infection 28.9%, syphilis 12.5%, gonorrhoea 1.7% and Chlamydia trachomatis 9.7%. More than 50% of non-immune MSW completed their three-dose hepatitis B vaccination course. Prevalence of STI is concordant with published data on MSW; this population clearly requests and deserves particular attention and approach. There is an important difference in sociodemographic and behavioural characteristics between MSW working in the red light district and those working on the street. Health promotion should be tailored to the different subpopulations and outreach appears to be a successful tool. [ABSTRACT FROM AUTHOR]

A 43-year-old man presented with abdominal discomfort caused by relapsing pancreatitis. Radiological examination revealed a multilocular cystic mass in the tail of the pancreas, which was resected. Gross examination showed a multilocular cystic lesion measuring 2.5 cm in diameter and containing clear fluid. Microscopically, a mucinous cystadenoma with mesenchymal stroma was diagnosed. The lesion showed two different components: a cyst lined by a columnar, mucin-secreting epithelium and a moderate cellular stroma composed of spindle cells. The stromal element appeared similar to primitive mesenchyme. Immunohistochemical staining confirmed this origin through vimentin expression and showed moderate to strong nuclear staining with oestrogen and progesterone receptor antibodies. Cystadenomas are rare tumours of the pancreas, but mesenchymal stroma is uncommon in such tumours; it is more frequently described in the liver and the bile ducts, and primarily in women. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Offering the vaccine and accepting it: an audit of hepatitis B vaccination in West Midlands region," by H. Jaleel, P. S. Allan, M. Huengsberg and D. Natin that was published in a previous issue of the periodical.

This article focuses on a study related to HPV in cervix and vagina. Cervical cancer screening by Papanicolaou smear has shown its use in reducing both incidence and mortality. Nowadays, cervical tumors are mostly diagnosed in women who were not, or not properly, screened. The invasive sampling method of screening is one of the reasons why women do not participate. The efficiency of cervical cancer screening could be increased if a less invasive test were available. This study aimed to investigate HPV prevalence in cervix and vagina on samples taken by a professional.

Presents information on the clinical case of an 11-year-old girl with ethosuximide associated systemic lupus erythematosus. Results of the laboratory investigation; Analysis of urine samples; Relationship between anticonvulsants and the appearance of lupus.