Training of young medical professionals: implementation of modern training concepts, taking into account the changed framework conditions for training-a pilot project for operational subjects.

INTRODUCTION: For years, generations of medical students have complained that practice-oriented learning is neglected in medical studies. Further training assistants also complain about limited opportunities to learn subject-specific practical activities. MATERIAL AND TECHNIQUES: We are presenting a pilot project at the University Women's Hospital in Homburg, in which medical students complete an endoscopic hands-on course as part of the block internship gynaecology and obstetrics. During the course the students perform classic skills training and hand-eye coordination exercises and learn the first steps in endoscopic suturing (suture and rows of knots). The training concepts used can be implemented on simple boxing trainers and can therefore also be reproduced in clinics or in a private setting. OUTCOME: Altogether, 73 medical students did participate in the laparoscopy course. We were able to prove that the knotting time for a simple knot can be reduced from an average of 247 s to 40 s (80%) after completing our training programme. Based on the evaluation sheet that the students filled out after the course, we found a very-high acceptance for surgical simulation training within the student cohort. DISCUSSION: Practical surgical exercises can complement the curriculum well and, as we can show with our work, are rated very positively by the students. For students in higher semesters, such practical courses can also provide an insight into the respective subject area and thus counteract the lack of skilled workers in surgical subjects. The practical year should not be the first contact with these practical courses, as at this timepoint a certain favoured subject has often already being chosen by the students.

The impact of gardening on well-being, mental health, and quality of life: an umbrella review and meta-analysis.

BACKGROUND: Gardening and horticultural therapy (HT) has been widely recognised as a multicomponent approach that has affected a broad range of health and well-being outcomes. The aim of this umbrella review and meta-analysis was to compare the findings of previous reviews on the impact of multiple gardening interventions and gardening attributes on different well-being constructs. METHODS: Electronic databases including PubMed, Web of Science, Science Direct, the Cochrane Library, and Google Scholar were searched from inception to December 2022. Interventional and observational reviews were eligible for inclusion in this umbrella review. Outcome measures included mental well-being, health status and quality of life. The key exposure variables were gardening and horticultural therapy. Narrative synthesis was used to evaluate the overall impact of gardening and HT on study outcomes. For a subsample of studies with available quantitative data, a random effect meta-analysis was conducted. RESULTS: This umbrella review included 40 studies (10 interventional studies, 2 observational studies, and 28 mixed interventional and observational studies). The reviewed studies reported an overall positive impact of gardening activities on several measures of mental well-being, quality of life, and health status. Meta-analysis showed a significant and positive effect of gardening and HT activities on well-being (effect size (ES) 0.55, 95% confidence interval (CI) 0.23, 0.87, p < 0.001). CONCLUSIONS: Evidence from observational and interventional studies supports a positive role for gardening and HT activities on well-being and general health. Interventional studies with horticultural-based therapies were effective in improving well-being and quality of life both in the general population and vulnerable subgroups. The high degree of heterogeneity in the included studies cautions against any direct clinical implications of the study findings.

SPONTANEOUS CONCEPTION AFTER CYCLE PROGRAMMING WITH DROSPIRENONE - A NEW OPTION FOR FERTILITY TREATMENTS.

More and more couples are postponing their desire to have children until later periods in life. This is accompanied by a variety of both, medical and social problems. It is known that fertility in women begins to decline gradually from the age of 25 and decreases rapidly from the age of 35. On the other hand, many couples in the fourth decade of life are significantly involved in their careers and are sometimes even physically separated. This means that the probability of conception is inherently reduced, because sexual intercourse cannot take place regularly on fertile days. We report on a 35-year-old patient in whom we programmed the cycle with the progestin pill drospirenone, which resulted in a spontaneous conception and the birth of a healthy child.

WOMEN AND MEN WITH CANCER AND A FUTURE DESIRE FOR CHILDREN - WHAT SHOULD CLINICIANS CONSIDER IN COVID-19 PANDEMIC TIMES?

The topic of fertility preservation has been gaining increasing importance since the beginning of this century. The reasons for this development are the advances in oncological therapy over the past few decades, with cure rates of approximately over 90%, and the fact that starting families is increasingly postponed in later periods of life in industrialized countries. Since March 2020 the whole medical and non-medical world experiences a pandemic due to Covid-19 (coronavirus disease 2019) which has never been seen before. This created a plenty of challenges for both, the patients and healthcare providers. This review article presents the fertility-protective methods currently available for women and men suffering from cancer with their clinical approach, value, advantages and disadvantages. Besides, it focuses on the changes and special considerations which have to be taken into account during pandemic times including preventive measures as well as the patient's access to the fertility preserving options. In conclusion every premenopausal woman and every man with incomplete family planning suffering from cancer should be counselled about the existing fertility preserving techniques before commencing cancer therapy.

Investigating BB0405 as a novel Borrelia afzelii vaccination candidate in Lyme borreliosis.

BB0405 is a surface exposed Borrelia burgdorferi protein and its vaccination protected mice against B. burgdorferi infection. As BB0405 is highly conserved across different B. burgdorferi sensu lato species, we investigated whether vaccination with recombinant BB0405 or through intradermal bb0405 DNA tattoo vaccination could provide protection against different Borrelia species, specifically against Borrelia afzelii, the predominant B. burgdorferi sensu lato genospecies causing Lyme borreliosis across Eurasia. We immunized C3H/HeN mice with recombinant BB0405 or with a codon-optimized bb0405 DNA vaccine using the pVAC plasmid and immunized corresponding control groups mice with only adjuvant or empty vectors. We subsequently subjected these immunized mice to a tick challenge with B. afzelii CB43-infected Ixodes ricinus nymphs. Upon vaccination, recombinant BB0405 induced a high total IgG response, but bb0405 DNA vaccination did not elicit antibody responses. Both vaccine formulations did not provide protection against Borrelia afzelii strain CB43 after tick challenge. In an attempt to understand the lack of protection of the recombinant vaccine, we determined expression of BB0405 and showed that B. afzelii CB43 spirochetes significantly and drastically downregulate the expression of BB0405 protein at 37 °C compared to 33 °C, where as in B. burgdorferi B31 spirochetes expression levels remain unaltered. Vaccination with recombinant BB0405 was previously shown to protect against B. burgdorferi sensu stricto. Here we show that vaccination with either recombinant BB0405 (or non-immunogenic bb0405 DNA), despite being highly conserved among B. burgdorferi sl genospecies, does not provide cross-protection against B. afzelii, mostly likely due to downregulation of this protein in B. afzelii in the mammalian host.

Depressive and anxiety symptomatology among people with asthma or atopic dermatitis: A population-based investigation using the UK Biobank data.

The present study investigated the association of depression and anxiety symptomatology (DAS) with asthma and atopic dermatitis (AD) diagnosis during mid-adult years. The study employed data from 502,641 participants in the UK Biobank. Neutrophils to Lymphocytes Ratios (NLRs) of patients with asthma and AD were calculated and evaluated in relation to DAS, measured via the Patient Health Questionnaire-4 (PHQ-4). Age of asthma or AD onset association with DAS were also estimated. Multivariable regression analyses were implemented among participants with asthma or AD, compared to those without these disorders. Out of 58,833 participants with asthma and 13,462 with AD, the prevalence of DAS was 11.7% and 2.7%, respectively. DAS increased among participants with either asthma or AD, being highest within patients having both (ß = 0.41, 95% confidence interval (95%CI), 0.34,0.49). NLR showed a linear increase with PHQ scores in asthma patients, (tertile 1, ß = 0.30, 95% CI, 0.27,0.34; tertile 2, ß = 0.36, 95%CI, 0.32,0.39, and tertile 3, ß = 0.43, 95%CI, 0.39,0.46). An inverted U-shaped association was seen between age of asthma onset and PHQ, with the 40-59 age group (ß = 0.54, 95%CI, 0.48,0.59) showing the highest risk followed by the 60+ (ß = 0.43, 95%CI, 0.34,0.51 and 20-39 groups (ß = 0.32, 95%CI, 0.27,0.38). Similar patterns emerged within AD. Asthma and AD were associated with increased DAS during mid-adult years, being strongest among participants reporting both disorders. A dose-response relationship between NLR and DAS was observed. Asthma or AD onset during mid-adult years (40-59) were associated with the highest increment in DAS.

Defining the Anatomy of the Tendinous Intersections of the Rectus Abdominis Muscle and Their Clinical Implications in Functional Muscle Neurotization.

PURPOSE: Little is known about the definitive course of the tendinous intersections from anterior to posterior through the rectus abdominis (RA) muscle. The implications of a full thickness intersection may have effects on the ability to neurotize the RA. We hypothesized that these tendinous inscriptions would be fully adherent to the anterior rectus sheath, but there would be an incomplete penetrance into the posterior surface, thereby allowing for muscle fibers and neurovascular structures to run the entire course of the RA muscle. METHODS: Fifty-five cadaveric, hemiabdominal walls were evaluated. Measurements were taken of RA muscle thickness, depth of penetrance of the tendinous intersections, and intersection thickness. RESULTS: Of the 32 cadavers, 2 had 4 paired tendinous intersections and the remaining 30 cadavers had 3 paired tendinous intersections. Rectus abdominis muscle belly tended to be thicker at midbelly, between intersections than at the level of the corresponding intersection. A total of 168 tendinous intersections were assessed. Thirty (18%) of these inscriptions proved to be full thickness extending from anterior rectus sheath to posterior rectus sheath without any intervening muscle or neurovascular structures. Twenty-three (42%) of the 55 hemiabdomens assessed had at least one full-thickness tendinous intersection. CONCLUSIONS: The majority of RA muscles have 3 paired tendinous intersections. Most intersections are incomplete and only encompass the anterior rectus sheath. However, there may be a higher percentage of full-thickness intersections than previously appreciated and the clinical relevance behind these remains unclear.

Discovery of the CCR1 antagonist, BMS-817399, for the treatment of rheumatoid arthritis.

High-affinity, functionally potent, urea-based antagonists of CCR1 have been discovered. Modulation of PXR transactivation has revealed the selective and orally bioavailable CCR1 antagonist BMS-817399 (29), which entered clinical trials for the treatment of rheumatoid arthritis.

Laparoscopic myomectomy.

Uterine leiomyoma is the most common benign tumour occurring in women in the reproductive age. It is typically found during the middle and later reproductive years. The prevalence quoted in literature ranges from 20-50% based on post mortem studies. The symptoms usually reported by women with fibroids are the following: abnormal gynaecologic haemorrhage, chronic pelvic pain, dyspareunia, as well as urinary and bowel symptoms, urinary frequency or retention and, in some cases, infertility. During pregnancy, premature labor might be caused, interfering with the position of the fetus or abortion could be induced. However, only 30% of the women develop symptoms, most of them being asymptomatic. It was proved that the factors that can cause fibroids are the following: genetic, hormonal, and growth factors, especially transforming the growth factor beta (TGFb)-related cellular changes. As diagnosis tools, studies are revealing that ultrasound has been shown to be an insufficient method of myoma mapping, and magnetic resonance imaging should be preferred for surgical therapy planning. The contour of the endometrial cavity is delineated by using trans vaginal ultrasound and saline infusion hysterosonography, but hysteroscopy is the gold standard to evaluate the uterine cavity.

The discovery of BMS-457, a potent and selective CCR1 antagonist.

A series of compounds which exhibited good human CCR1 binding and functional potency was modified resulting in the discovery of a novel series of high affinity, functionally potent antagonists of the CCR1 receptor. Issues of PXR activity, ion-channel potency, and poor metabolic stability were addressed by the addition of a hydroxyl group to an otherwise lipophilic area in the molecule resulting in the discovery of preclinical candidate BMS-457 for the treatment of rheumatoid arthritis.

Peripheral neuropathy in Whipples disease: a case report.

Whipples disease is a chronic multisystem inflammatory disease with predominantly gastrointestinal manifestations due to Tropheryma whipplei infection. Typical neurological abnormalities include dementia, eye movement abnormalities, hypothalamic dysfunction and oculomasticatory myorhythmias. The literature on peripheral neuropathy in Whipples disease is sparse and the involvement of peripheral nerves in Whipples disease has not been documented convincingly so far. We present a case of Whipples disease presenting by axonal peripheral neuropathy without gastrointestinal involvement. The diagnosis was confirmed by a sural nerve biopsy and consequent PCR of the sample. All clinical signs disappeared progressively during the antibiotic therapy. Two years after the T. whipplei infection, the patient developed dopa-sensitive Parkinson's disease, although these two events seem to be unrelated. This case illustrates the value of peripheral nerve biopsy in cases of axonal neuropathy of unexplained origin and extends the clinical spectrum of Whipples disease to a new modality.

[Carney complex]. / Carneyho komplex.

Carney complex is a clinically and genetically heterogeneous disease, with at least two genetic loci including the PRKAR1A gene located on chromosome 17 and the CNC2 locus mapped to chromosome 2. Clinically this syndrome is characterized by multiple myxomas occurring in different anatomic sites, mucocutaneous pigmentary lesions, and a variety of non-endocrine and endocrine tumors, often causing endocrine abnormalities, involving various organs. Knowledge of morphological findings in CNC patients with their typical locations is necessary to raise suspicion of this syndrome by pathologists. Confirmation of the diagnosis allows regular clinical check-ups and early treatment of these patients.

Leukaemia inhibitory factor (LIF) gene mutations in women diagnosed with unexplained infertility and endometriosis have a negative impact on the IVF outcome. A pilot study.

The frequency of functionally relevant mutations of the leukaemia inhibitory factor (LIF) gene in infertile women is significantly enhanced in comparison with fertile controls. The objective of this retrospective cohort study was to evaluate the impact of LIF gene mutations on the outcome of the treatment in women with various causes of infertility. Fifteen infertile women with the G to A transition at position 3400 leading to the valine to methionine exchange at codon 64 were analysed. Group A was made up of women with diagnoses that are frequently accompanied by changes in humoral as well as cell-mediated immunity - idiopathic infertility and endometriosis (N = 7). Group B consisted of patients with polycystic ovary syndrome (PCOS), andrological factor, tubal factor and hyperprolactinaemia (N = 8). The control group comprised 136 infertile women with no LIF gene mutation diagnosed with idiopathic infertility and endometriosis (N = 37) (group C) and patients with PCOS, tubal and andrological factor (N = 99) (group D). Seven of the mutation-positive patients were successfully treated by in vitro fertilization (IVF), but nobody in this group was diagnosed with idiopathic infertility and only one with endometriosis, which means that there is a statistically significant difference in the pregnancy rates between groups A and B (P = 0.01, Fisher's 2 by 2 exact test) but no statistically significant difference when comparing patients with the LIF gene mutation (group A+B) to no LIF gene mutation (group C+D). The results suggest that in mutation-positive women the idiopathic infertility and endometriosis have a negative impact on the outcome of IVF treatment.

Renal angiomyoadenomatous tumor: morphologic, immunohistochemical, and molecular genetic study of a distinct entity.

We present a series of a distinct tumorous entity named renal angiomyoadenomatous tumor (RAT). Five cases were retrieved from the consultation files of the authors. Histologic and immunohistochemical features were evaluated. Sequencing analysis of coding region of the VHL gene was carried out in all cases. The tumors were composed of admixture of an epithelial clear cell component and prominent leiomyomatous stroma. Epithelial cells formed adenomatous tubular formations endowed with blister-like apical snouts. All tubular/glandular structures were lined by a fine capillary network. The epithelial component was positive for epithelial membrane antigen, CK7, CK20, AE1-AE3, CAM5.2, and vimentin in all cases. In all analyzed samples, no mutation of the VHL gene was found. RAT is a distinct morphologic entity, being different morphologically, immunohistochemically, and genetically from all renal tumors including conventional clear cell carcinoma and mixed epithelial and stromal tumor of kidney.

[Intraneural perineurioma: clinical and morphological characteristics and a molecular genetic study of the neurofibromatosis type 2 gene].

The authors describe 4 cases of clinically, morphologically, and immunohistochemically typical intraneural perineuriomas that occurred in women aged 17 to 24 years. The tumors involved median, radial, ulnar, and palmar nerves and were 3, 2.5, 1.5, and 1.2 cm in the largest diameter. None patients had signs ofneurofibromatosis type 2 (NF2). One case was studied for mutation of the NF2 gene and heterozygous splice-site mutation at the acceptor splice site between exons 12 and 13 (agGG --> aaGG) was revealed. Two patients were followed up: they were disease-free for 10 and 15 years.

Endolymphatic sac tumor (aggressive papillary tumor of middle ear and temporal bone): report of two cases with analysis of the VHL gene.

Endolymphatic sac tumor (Heffner tumor) (ELST) is a very rare nonmetastasizing, locally aggressive low-grade adenocarcinoma of endolymphatic sac origin, which is linked to von-Hippel-Lindau disease (VHLD). VHLD is an autosomal dominant disorder characterized by an inherited genetic abnormality of the VHL gene located on the short arm of chromosome 3 (3p26-p25). VHL gene mutations have been shown both in ELSTs associated with VHLD and in sporadic cases. Because of the rarity of ELST, only a small number of cases have been subjected to molecular genetic analysis. We have encountered two patients with ELST, one of whom presented with a medical and family history of VHLD. The second was a sporadic case, the patient having no symptoms of VHLD. The tissues obtained from Heffner tumor and cerebellar hemangioblastoma from the patient with inherited VHLD possess a point mutation in exon 1 of VHL gene. This mutation is a C to T exchange at position 194, resulting in amino acid exchange S65L. No mutation was found in any of the three exons analyzed and in the exon-intron junctions of the VHL gene in the sporadic case.

[The leukemia inhibitory factor gene mutations in the population of infertile women: the heterozygote transition G to A on the position 3400 does not affect the outcome of the infertility treatment]. / Mutace v genu pro leukemický inhibicní faktor v populaci neplodných zen: heterozygotní bodová zámena G za A na pozici 3400 neovlivnuje úspesnost lécby.

OBJECTIVE: The leukemia inhibitory factor (LIF) is one of the most important signaling factors in the embryo-maternal cross talk during the embryo implantation. We investigated the prevalence of the LIF gene mutations in the population of infertile women and their impact on infertility treatment. DESIGN: A cohort study. SETTING: Department of Obstetrics and Gynecology, Faculty of Medicine and University Hospital of Charles University, Pilsen. SUBJECTS AND METHODS: The population to screen consisted of 399 infertile women. The control population was comprised of 202 healthy fertile subjects. For the mutational analysis, the temperature gradient gel electrophoresis (TGGE) followed by subsequent sequencing of the positive samples, had been used. The groups of fertile controls and infertile patients were compared for statistically significant difference using the Fisher's 2 by 2 Exact test. RESULTS: Twelve potentially functional LIF gene mutations, the G to A transversion at the position 3400 leading to the valin to methionin exchange at codon 64 (V64M) were detected in the group of infertile women. No mutations were identified in the control group, which means that the frequency of functionally relevant mutations of the LIF gene in infertile women is significantly enhanced in comparison with controls (P = 0.01, Fisher's 2 by 2 Exact test ). Seven of these patients were successfully treated by in vitro fertilization (IVF). CONCLUSION: The results suggest that the LIF gene mutation, the heterozygote G to A transition on the position 3400, affects fertility but the infertility treatment can succeed. Even though LIF gene mutations occur infrequently and can be overcome by infertility treatment, their impact on molecular events during early phases of pregnancy should be further elucidated.

Diaryl substituted pyrazoles as potent CCR2 receptor antagonists.

We have identified and synthesized a series of diaryl substituted pyrazoles as potent antagonists of the chemokine receptor subtype 2. Structure-activity relationship studies directed toward improving the potency led to the discovery of 23 (IC50 = 6 nM).

Association of the leukemia inhibitory factor gene mutation and the antiphospholipid antibodies in the peripheral blood of infertile women.

To characterize the impact of the potentially functional mutation--the G to A transition at the position 3400 of the leukemia inhibitory factor (LIF; a pluripotent cytokine that plays a central role in the control of the embryo implantation) gene that leads to the exchange of valine with methionine at codon 64 we evaluated the association of the LIF gene mutation and the levels of antiphospolipid antibodies (aPLs) in the peripheral blood of infertile women (the aPLs examination was part of our routine immunological test during the infertility check-up). Eight infertile mutation-positive women were diagnosed with idiopathic infertility (n=5) and endometriosis (n=3) and their levels of aPLs in serum were compared with 115 infertile women without any LIF gene mutation. Enzyme-linked immunosorbent assay was used for the detection of seven antiphospholipid antibodies; the results were statistically assessed by the Fisher's 2 by 2 exact test to evaluate the association of the LIF gene mutations and aPLs in serum of infertile patients. The presence of aPLs was significantly higher in our study group (100%) than in 30% of aPLs-positives in control infertile patients (p = 0.0035) which indicates that the aPLs are elevated in women with LIF gene mutations.