Measurement protocols and determinants of peak oxygen consumption in adults with Down syndrome: a systematic review.

This systematic review aimed to provide an overview of test protocols used to measure peak oxygen uptake (VO2peak) in adults with Down syndrome (DS) and to determine how generalisable the outcomes are for the entire population of adults with DS by describing the sample characteristics of these studies and their impact on VO2peak. A literature search (PROSPERO CRD42022309560) was performed (18 July 2023) using the following databases: PubMed, CINAHL, APA PsycINFO, Web of Science, Embase and SPORTDiscus. For articles to be included, they had to be peer-reviewed pubications, reporting VO2peak or VO2max for individuals with DS separately, with a sample of n ≥ 5 and a mean age ≥18 years. Systematic reviews and meta-analyses were excluded but their reference lists were searched for additional papers to include. Studies were evaluated for risk of bias following the guidelines of Kmet et al. The results were summarised with frequency statistics. Forty-three studies were included in this systematic review. Sample sizes of included adults with DS ranged from n = 4-226, with a total of n = 1498 adults with DS being included. Most studies (29/43) used the same standardised maximal exercise treadmill protocol to measure VO2peak in adults with DS, and 33 out of 43 studies used at least one objective criterion to determine a valid maximal effort. Participants were predominantly male, under 40 years old, and overweight or obese. Additionally, the diversity of study samples was lacking or not reported. The most widely used, standardised, maximal exercise test treadmill protocol is recommended for future use in research and practice, including objective criteria to determine valid maximal effort. The current study samples are not representative of the population of adults with DS in terms of sex, age and diverse backgrounds and therefore likely overestimate VO2peak of this population.

Comprehensive cardiopulmonary profile of individuals with Down syndrome.

BACKGROUND: Individuals with Down syndrome (DS) have low levels of cardiorespiratory fitness and previous studies have shown that these low levels of fitness have a physiological cause. During exercise, the cardiovascular, ventilatory and muscular systems are simultaneously active. While individual parameters of these systems have been investigated in DS before, the interaction between these parameters and systems have not been discussed in detail. Doing so may provide important insight regarding the aetiology of low cardiorespiratory fitness and which parameters of the cardiovascular, pulmonary and muscular systems are altered in individuals with DS compared with their peers without DS. METHODS: Cardiopulmonary exercise tests were performed in healthy adults with and without DS. Parameters related to the cardiovascular, ventilatory and muscular systems were collected until VO2peak . In total, 51 participants were included in analysis, of which 21 had DS. RESULTS: Individuals with DS showed lower peak values for all collected outcomes (P ≤ 0.001) compared with those without DS, except for ventilatory threshold as a percentage of maximal oxygen uptake and VE /VCO2 slope, which were similar. CONCLUSIONS: Our results show that individuals with DS present impairments across the cardiovascular, ventilatory and muscular aspects of the cardiopulmonary system.

Anthropometry does not fully explain low fitness among adults with Down syndrome.

BACKGROUND: Cardiorespiratory fitness, expressed as peak oxygen uptake during exercise (VO2 peak), is an important predictor of cardiovascular health and is related to anthropometry in the general population. Individuals with Down syndrome (DS) have reduced cardiorespiratory fitness and often exhibit different anthropometrics compared with the general population. Interestingly, the relation between anthropometry and cardiorespiratory fitness found in the general population is not apparent in individuals with DS. However, accurate measures with dual energy X-ray absorptiometry (DEXA) scan have not been used to investigate this relationship in this population. The purpose of this paper was to investigate the relationship between accurate measures of anthropometry and cardiorespiratory fitness in adults with DS compared with an age-matched and sex-matched control group. METHODS: Anthropometrics (height, weight, waist and hip circumference, body composition via DEXA) and cardiorespiratory fitness (VO2 peak, measured during a graded maximal exercise test) were assessed in adults with (n = 9; 25 ± 3 years; 6 male patients) and without DS (n = 10, 24 ± 4 years; 5 male patients). RESULTS: Participants with DS were shorter (P < 0.01) than without DS and had a higher body mass index (P < 0.01), waist circumference (WC) (P = 0.026) and waist/height ratio (WHtR) (P < 0.01), but similar weight, body surface area (BSA), waist/hip ratio and body composition (P > 0.05). Participants with DS had significantly lower relative VO2 peak and VO2 peak corrected for total lean mass (TLM), but similar absolute VO2 peak, compared with without DS. In participants with DS, only WC and WHtR were associated with VO2 peak, whereas in participants without DS, height, weight, BSA, TLM, leg lean mass and body fat percentage were associated with VO2 peak. CONCLUSIONS: These results suggest that the relation between anthropometry and cardiorespiratory fitness found in the general population is not the same in adults with DS and that anthropometrics do not fully explain cardiorespiratory fitness in adults with DS. Further research into potential alternative explanations is required.

The remains of the taboo: experiences, attitudes, and knowledge about menopause in the workplace.

Objectives: This study explored experiences of, attitudes to, and knowledge about menopause in the workplace among participants from the UK to assess the extent to which menopause remains a taboo in this context.Method: An online survey was distributed via Trades Union Congress, UK networks and social media, and was completed by 5399 respondents. Questions explored three key issues relating to menopause at work: respondents' own experiences of menopause transition; disclosure at work; and availability of information on menopause at work.Result: The largest group (43.4%) of respondents were perimenopausal and 16.8% were postmenopausal; 12.3% indicated that they might be experiencing menopause but were not sure. Only 45.8% had disclosed their menopause status at work. Fewer than 20% were provided with information about menopause in their workplace but the majority would like such information to be available.Conclusion: The survey findings suggest some progress has been made to raise awareness about menopause in the workplace but that substantial work remains to be done to ensure women transitioning through menopause are supported.

[Management of ureteral injuries]. / Management von Harnleiterverletzungen.

Ureteral injuries account for less than 3% of genitourinary injuries. Most of them are caused iatrogenically during abdominal surgery. The symptoms are often non-specific and do not aid in diagnosis. The later the injury is detected, the more often complications occur. Therefore, in such situations it is important to consider the possibility of ureteral injury and initiate further diagnostic steps as soon as possible. A variety of diagnostic tests are available. In addition to the direct inspection of the ureters and retrograde ureteropyelography, computed tomography (CT) urography is routinely used. Based on the time of diagnosis as well as the extent and the localization of the injury, the further procedure can be determined. For minor injuries, the insertion of a ureteral splint is usually the treatment of choice. In the case of higher grade damage, operative reconstruction by one of several possible surgical procedures is indicated.

[Stricture of the vesicourethral anastomosis after radical prostatectomy]. / Die Striktur der vesikourethralen Anastomose nach radikaler Prostatektomie.

BACKGROUND: The development of a stricture of the vesicourethral anastomosis is a serious complication after radical prostatectomy. Strictures occur in 5-8% of patients after radical prostatectomy. SYMPTOMS: Usually the clinical symptoms include an irritative and obstructive component similar to benign prostatic hyperplasia. In rare cases, patients suffer from partial or complete stress incontinence as a result of the anastomotic stricture. DIAGNOSTICS: The diagnostic workup is similar to the procedure for urethral strictures. In addition to uroflowmetry, a cystourethrogram (CUG) or, if necessary, a micturating cystourethrogram (MCU) can be performed. A urethrocystoscopy can be performed to ensure the diagnosis. THERAPY: In most cases, endoscopic procedures were performed for treatment. Beside a transurethral dilation of the stricture or the Sachse urethrotomy, the most common procedure is transurethral resection to treat the stricture. However, all procedures are associated with a high recurrence rate. In recurrent strictures, open surgical procedures, usually a perineal reanastomosis, should performed early. CONCLUSION: Endourological procedures like transurethral resection are a good treatment option, but due to the high recurrence rates, open surgical procedures should be discussed and if necessary should be performed early.

[Diagnostic workup of urethral strictures]. / Diagnostischer Workup bei der Harnröhrenstriktur.

Urethral stricture is a narrowing of the urethra due to scar tissue. It causes obstructive voiding dysfunction and can lead to long-term damage of the entire urinary tract. The probability of therapeutic success is dampened by a high rate of recurrence. Therefore, a careful taking of the patient's history and further diagnostics are crucial for finding the appropriate form of therapy. This review highlights the clinical presentation and diagnostic workup of urethral strictures.

[Urethral stricture : From diagnostics to appropriate treatment]. / Urethrastriktur : Von der Diagnostik bis zur sinnvollen Therapie.

Before making a treatment decision for patients presenting with a urethral stricture, following anamnesis and general examinations, appropriate diagnostics are necessary. This includes at least uroflowmetry and cystourethrography and the use of ultrasound and cystoscopy may be of additional help. The curative treatment of a urethral stricture is always an operation. Besides endourological procedures, open surgery for urethral reconstruction is also performed. This article aims to give an overview about the necessary diagnostic measures and the pros and cons of the different operative therapies.

[Current Aspects on the Pathogenesis of Urinary Tract Infections]. / Aktuelle Aspekte zur Pathogenese der Harnwegsinfektion.

Urinary tract infections are among the most common bacterial infectious diseases worldwide. Every second woman will experience at least one urinary tract infection in her lifetime. The administration of antibiotics has been a safe and efficient treatment modality so far. However, due to the emergence of multi-resistant pathogens and the developmental void of new antimicrobial drugs, the therapy of infections mighty become more challenging in the near future. So, knowledge of the complex host-pathogen interaction is of great importance. Common phenotypes observed in clinical practice suggest basic principles, which are relevant for the development of novel antimicrobial strategies. With invading pathogens forming intracellular bacterial communities they evade host response and provide a nidus for recurrent infection. A plethora of virulence factors allow uropathogenic bacteria to colonize and to establish infections in the urinary tract. In response, host responses seem to address specific virulence mechanisms that are essential to pathogenicity. Deciphering the molecular mechanisms underlying the complex host-pathogen interaction is critical to devise novel treatment options.

Factors associated with pain induced by orthodontic separators.

Pain resulting from the application of orthodontic forces varies markedly across individuals. The reasons of this variability are still largely unknown. To investigate factors that may be associated with orthodontic pain following the application of orthodontic separators. One hundred and seven participants were screened for pain response over 48 h following placement of orthodontic elastomeric separators. The highest (n = 10) and lowest (n = 10) pain responders were identified, and data collected on tooth pain sensitivity to electrical stimulation in conjunction with using the Pain Catastrophising Scale (PCS), Dental Anxiety Scale (DAS) and cold pressor test (CPT). There were statistically significant differences between high- and low-pain responders in catastrophising score (P ≤ 0.023). For every PCS magnification score of 1 unit higher, the relative risk of being a high-pain responder was 1.6 (P = 0.002); those scoring higher on helplessness had a lower risk of being so. DAS scores of high-pain responders were twice as high as those of low-pain responder (P = 0.043). During the first 2 min of CPT, the high-pain responders experienced more pain than the low-pain responders (P ≤ 0.029). Tooth pain thresholds did not differ between the two different pain responder groups. Pain catastrophising, dental anxiety and cold sensitivity appear to modify the pain experienced following placement of orthodontic separators. Further research is needed to determine the validity of screening questions to identify at-risk patients prior to commencing orthodontic treatment.

Impact of malocclusion on quality of life among New Zealand adolescents.

OBJECTIVES: To determine whether malocclusion is associated with oral-health-related quality of life (OHRQoL) in New Zealand adolescents. METHODS: Data from two cross-sectional epidemiological studies of adolescents in Taranaki and Otago were used. Each participant completed a self-administered questionnaire and underwent a clinical examination. Information collected included sociodemographic characteristics (sex, ethnicity and household deprivation), and clinical measures (caries and malocclusion, the latter measured with the Dental Aesthetic Index, or DAI). OHRQoL was measured using the validated 16-item impact short-form Child Perceptions Questionnaire (CPQ11-14). Linear regression was used to model the CPQ11-14 score. RESULTS: 783 adolescents (52.6% male) took part. One-fifth had a handicapping malocclusion and one-third had a minor malocclusion or none. The overall mean DMFS was 2.3 (SD, 3.8), with slightly more than 50% being caries-free. With the exception of the oral symptoms domain, females presented with higher mean CPQ11-14 and domain scores, while Mãori had lower scores. There was a distinct gradient in mean CPQ11-14 and domain scores across the categories of malocclusion severity, whereby those in the 'handicapping' category of the DAI had the highest CPQ11-14 score. Linear regression modeling of the CPQ11-14 score showed that, after controlling for DMFS and socio-demographic characteristics, malocclusion category and being female were positively associated with higher CPQ11-14 scores. CONCLUSION: A severe malocclusion appears to have a negative impact on the OHRQoL of New Zealand adolescents.

[Activity trails, risk of falling, and health-related quality of life. Effects of a 12-week guided intervention]. / Bewegungsparcours, Sturzrisiko und gesundheitsbezogene Lebensqualität : Effekte einer 3-monatigen Bewegungsintervention.

BACKGROUND: The purpose was to evaluate the interventional effects of activity trails (courses) on fall risk factors and health-related quality of life (hrQoL). MATERIALS AND METHODS: A total of 94 subjects (67.7 ± 5.7 years; 29 men, 65 women) completed the following measurements prior to and 12 weeks after the initiation of the activity trail intervention: maximum isometric leg extensors force (Fmax, m3 diagnoses©), gait velocity (GV), and static postural stability (STAB, Zebris FDM©), fall-associated self-efficacy (FALL, FES-I), and hrQoL (SF-36). RESULTS: During the 12-week intervention period, the participants increased Fmax (1.63 ± 0.6 vs. 1.70 ± 0.6 N•kg(-1)) and GV (1.06 ± 0.25 vs. 1.11 ± 0.18m•s(-1); p < 0.05). Neither FALL (19.44 ± 3.6 vs. 19.41 ± 4.3 points) nor STAB (84.3 ± 56.4 vs. 79.7 ± 63.1 mm(2)) changed. Additionally, significant improvements in hrQoL regarding vitality (56.3 ± 17.2 vs. 63.2 ± 18.3 points) and mental health (69.4 ± 18.7 vs. 75.5 ± 16.5 points; p < 0.05) were found. CONCLUSION: The improvements in fall-related risk factors and hrQoL may be expected to contribute to fall prevention and psychosocial quality of life.

Chicago aberration correction work.

The author describes from his personal involvement the many improvements to electron microscopy Albert Crewe and his group brought by minimizing the effects of aberrations. The Butler gun was developed to minimize aperture aberrations in a field emission electron gun. In the 1960s, Crewe anticipated using a spherical aberration corrector based on Scherzer's design. Since the tolerances could not be met mechanically, a method of moving the center of the octopoles electrically was developed by adding lower order multipole fields. Because the corrector was located about 15 cm ahead of the objective lens, combination aberrations would arise with the objective lens. This fifth order aberration would then limit the aperture of the microscope. The transformation of the off axis aberration coefficients of a round lens was developed and a means to cancel anisotropic coma was developed. A new method of generating negative spherical aberration was invented using the combination aberrations of hexapoles. Extensions of this technique to higher order aberrations were developed. An electrostatic electron mirror was invented, which allows the cancellation of primary spherical aberration and first order chromatic aberration. A reduction of chromatic aberration by two orders of magnitude was demonstrated using such a system.

Ontogenic expression profiles of thyroid-specific genes in embryonic and hatching chicks.

The last trimester of the embryonic life of chickens is marked by a steady increase in circulating thyroxine (T(4)) levels, reaching a maximum around hatching. We have measured thyroidal mRNA expression levels of several genes involved in the biosynthesis of T(4), namely sodium/iodine symporter (NIS), thyroglobulin (Tg), thyroid peroxidase (TPO), thyrotropin receptor (TSHR), and thyroid transcription factor 1 (TTF-1), during this period. Subsequently, we measured the expression of these genes in more detail during the entire hatching process and compared the gene expression profiles with concomitant changes in intrathyroidal and circulating thyroid hormone levels. We found that NIS and TPO mRNA expression increased significantly in the perinatal period, whereas Tg mRNA expression rose gradually throughout the last week of embryogenesis but was stable during hatching. TSHR and TTF-1 mRNA levels did not change significantly during the last week of embryonic development and hatching. Our results suggest that the elevated plasma T(4) levels observed in the developmental period studied are caused by an increased synthesis and secretion of T(4) by the thyroid gland. Augmented expression of Tg may play an important role in the increasing T(4) production during the last week of embryonic development, whereas increased NIS and TPO expression around hatching allows the thyrocytes to boost T(4) synthesis even further.

Bisphosphonate-induced osteonecrosis of the jaw (ONJ): Incidence and risk factors in patients with breast cancer and gynecological malignancies.

OBJECTIVE: Since 2003, multiple cases of bisphosphonate-induced osteonecrosis of the jaw (ONJ) were reported. The aim of this study was to describe the incidence and risk factors of ONJ in patients with breast cancer or gynecological malignancies receiving bisphosphonates (BP). METHODS: ONJ was recorded for all patients with breast cancer or gynecological malignancies treated with intravenous bisphosphonates at the Department of Gynecology and Obstetrics, University Hospital Tuebingen during April, 1999 and May, 2006. RESULTS: 10 of 345 (2.9%) patients with breast cancer or gynecological malignancies developed ONJ while receiving bisphosphonate therapy. Six patients with ONJ had a history of recent dental procedures. All patients had received zoledronic acid as part of their bisphosphonate regimen. Time of exposure to bisphosphonates and the number of treatment cycles were significant risk factors for the development of ONJ (p<0.001). In patients diagnosed with ONJ the mean number of treatment cycles was 27+/-18 cycles. However, the mean number of treatment cycles in patients without manifestation of ONJ was 12+/-12 cycles. CONCLUSION: Length of exposure to BPs and the cumulative dose of given BPs seem to be the most important risk factors for the development of ONJ followed by dental procedures.

Detection of disseminated tumor cells in patients with gynecological cancers.

OBJECTIVES: The presence of disseminated tumor cells (DTC) in breast cancer patients is associated with poor prognosis. However, there are limited data about the prevalence and prognostic impact of DTC in patients with gynecological tumors. The aim of this study was to evaluate the presence of DTC in the bone marrow (BM) of patients with gynecological cancers and to correlate their presence with established prognostic factors. METHODS: BM aspirates of 201 patients with primary ovarian (n=69), cervical (n=54) and endometrial cancer (n=78), undergoing surgery at the Department of Gynecology and Obstetrics, University Hospital, Tuebingen, Germany between 1/2002 and 01/2006, were included into the study. Cytokeratin (CK)-positive cells were identified by immunocytochemistry using the pancytokeratin antibody A45B/B3. RESULTS: The bone marrow positivity rate was 36% in ovarian, 26% in cervical and 17% in endometrial cancer, respectively. Presence of DTC was significantly correlated with FIGO (International Federation of Gynecology and Obstetrics) tumor stage (p<0.05). The recurrence rate was 14% in patients with CK-positive cells compared to 8% in CK-negative patients (p=0.2). There was no correlation between DTC and other established prognostic factors including nodal status or grading except for cervical cancer. Patients with positive lymph node status were more likely to be bone marrow positive compared to those with negative lymph node status (p<0.05). CONCLUSIONS: Disseminated tumor cells seem to be a general phenomenon in epithelial tumors even though their clinical impact remains to be evaluated. The hypothesis that bone marrow is the homing site of disseminated tumor cells is further supported by these data since gynecological tumors only rarely metastasize to the skeletal system.

Phytoestrogens derived from red clover: an alternative to estrogen replacement therapy?

The benefits of plant extracts from soy and red clover as alternatives to conventional hormone replacement therapy (HRT) have been debated in the past. Here, an attempt has been made to summarize the biochemical and pharmacological data in the light of clinical aspects. Red clover and soy extracts contain isoflavones, which have a high affinity to estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), progesterone receptor (PR) and androgen receptor (AR). The higher affinity to ERbeta compared to ERalpha has been used as an explanation why red clover extracts function as food additives to treat menopausal disorders and may reduce risk of breast cancer. Biochemical analysis shows that these representatives of phytoestrogens have multiple actions beside selective estrogen receptor modulator (SERM)-activity. They act as selective estrogen enzyme modulators (SEEMs), have antioxidant activity and interact with transcription factors such as NF-kappaB. Furthermore, it is indicated that they have protective effects on osteoporosis and the cardiovascular system. Currently 40-50mg of isoflavones (biochanin A, daidzein, formononetin and genistein) are recommended as daily dose. This recommendation is based on the daily intake of phytoestrogens in a traditional Japanese diet.

Interaction of PCBs with thyroid hormone levels and time of hatching in chicken embryos.

The effects of polychlorinated biphenyls (PCB 77, PCB 153, and the mixture Aroclor 1242) on circulating and intracellular thyroid hormone (TH) levels were studied during chicken embryonic development. We observed no influences of PCB 153 on TH availability. Aroclor 1242 caused a transient increase in the T(3) level in the cerebellum at day 16. Clear effects were only seen with PCB 77 around the period of hatching: a severely reduced TH peak, which normally coincides with the stage of internal pipping, and a considerable delay in the moment of hatching.

Neurotoxicity of polychlorinated biphenyls (PCBs) by disturbance of thyroid hormone-regulated genes.

PCBs are known as neurotoxic compounds. Part of this neurotoxicity could be due to an alteration of the expression of TH-regulated genes in brain. To identify such genes, brain protein extracts of hypo- and hyperthyroid as well as PCB-treated embryos were compared by fluorescent 2D-DIGE. In total, we observed 109 differentially expressed proteins, of which 17 differed with both PCB and hypo- or hyperthyroid treatment. It was found that the interaction of PCBs with the expression of TH-regulated genes is congener-specific and that both hyperthyroidism- and hypothyroidism-related effects occur.