Ameliorative potential of rosmarinic acid in a rat model of polycystic ovary syndrome: Targeting MCP-1 and VEGF: A histological, immunohistochemical, and biochemical study.

Polycystic ovary syndrome (PCOS) is a multidisciplinary endocrinopathy that affects women of reproductive age. It is characterized by menstrual complications, hyperandrogenism, insulin resistance, and cardiovascular issues. The current research investigated the efficacy of rosmarinic acid in letrozole-induced PCOS in adult female rats as well as the potential underlying molecular mechanisms. Forty female rats were divided into the control group, the rosmarinic acid group (50 mg/kg per orally, po) for 21 days, PCOS group; PCOS was induced by administration of letrozole (1 mg/kg po) for 21 days, and rosmarinic acid-PCOS group, received rosmarinic acid after PCOS induction. PCOS resulted in a marked elevation in both serum luteinizing hormone (LH) and testosterone levels and LH/follicle-stimulating hormone ratio with a marked reduction in serum estradiol and progesterone levels. A marked rise in tumor necrosis factor-α (TNF-α), interleukin-1ß, monocyte chemotactic protein-1, and vascular endothelial growth factor (messenger RNA) in the ovarian tissue was reported. The histological analysis displayed multiple cystic follicles in the ovarian cortex with markedly thin granulosa cell layer, vacuolated granulosa and theca cell layers, and desquamated granulosa cells. Upregulation in the immune expression of TNF-α and caspase-3 was demonstrated in the ovarian cortex. Interestingly, rosmarinic acid ameliorated the biochemical and histopathological changes. In conclusion, rosmarinic acid ameliorates letrozole-induced PCOS through its anti-inflammatory and antiangiogenesis effects.

Competence of Combined Low Dose of Human Chorionic Gonadotropin (HCG) and Clomiphene Citrate (CC) Versus Continued CC during Ovulation Induction in Women with CC-Resistant Polycystic Ovarian Syndrome: A Randomized Controlled Trial.

Background and Objectives: Polycystic ovarian syndrome (PCOS) is a widespread endocrine disorder affecting 5-18% of females in their childbearing age. The aim of this study is to assess the efficacy of combining a low dosage of human chorionic gonadotropin (HCG) along with clomiphene citrate (CC) for stimulating ovulation in infertile women diagnosed with CC-resistant PCOS. Materials and Methods: A randomized controlled trial was carried out on 300 infertile CC-resistant PCOS women. All participants were assigned to two groups: the CC-HCG group and the CC-Placebo group. Subjects in the CC-HCG group were given CC (150 mg/day for 5 days starting on the 2nd day of the cycle) and HCG (200 IU/day SC starting on the 7th day of the cycle). Subjects in the CC-Placebo group were given CC and a placebo. The number of ovarian follicles > 18 mm, cycle cancellation rate, endometrial thickness, ovulation rate, clinical pregnancy rate, and occurrence of early ovarian hyper-stimulation syndrome were all outcome variables in the primary research. Results: Data from 138 individuals in the CC-HCG group and 131 participants in the CC-Placebo group were subjected to final analysis. In comparison to the CC-Placebo group, the cycle cancellation rate in the CC-HCG group was considerably lower. The CC-HCG group exhibited a substantial increase in ovarian follicles reaching > 18 mm, endometrial thickness, and ovulation rate. The clinical pregnancy rate was higher in the CC-HCG group (7.2% vs. 2.3%; CC-HCG vs. CC-Placebo). Upon adjusting for BMI and age, the findings of our study revealed that individuals in the CC-HCG group who had serum prolactin levels below 20 (ng/mL), secondary infertility, infertility duration less than 4 years, baseline LH/FSH ratios below 1.5, and serum AMH levels more than 4 (ng/mL) had a higher likelihood of achieving pregnancy. In the CC-Placebo group, there was a greater prediction of clinical pregnancy for those with serum AMH (<4), primary infertility, serum prolactin ≤ 20 (ng/mL), baseline LH/FSH < 1.5, and infertility duration < 4 years. Conclusions: The use of a small dose of HCG along with CC appeared to be an effective treatment in reducing cycle cancelation, improving the clinical pregnancy rate and ovulation rate in CC-resistant PCOS patients. The trial was registered with Clinical Trials.gov, identifier NCT02436226.

TERFs aren't feminists: lesbians stand against trans exclusion.

In this article, I examine lesbians' solidarity with trans people in the United States. Trans exclusionary radical feminists (TERFs) are feminists who believe that there is a stark difference between the biological reality of sex and the socially constructed nature of gender. They argue that sex is essential and innate. This leads some feminists to the argument that trans people are trying to infiltrate sex exclusive spaces. While TERFs are not always lesbians, lesbians are assumed to make up a large proportion of TERFs. As Thomsen and Essig argue that current ideologies within the media are allowing for the slippage between the terms "lesbian," "feminist," and "TERFs." Some scholars are suggesting that equating lesbian identities with transphobia and trans exclusion is but a new form of lesbian marginalization. I utilize 49 in-depth, qualitative interviews with lesbians across the United States to interrogate the stereotype that lesbians are largely TERFs. Through the voices of lesbians across the United States, I illustrate how many lesbians despise TERF ideology and argue that lesbians must stand in solidarity with trans people in the fight for social justice.

Increased length-dependent activation of human engineered heart tissue after chronic α1A-adrenergic agonist treatment: testing a novel heart failure therapy.

Chronic stimulation of cardiac α1A-adrenergic receptors (α1A-ARs) improves symptoms in multiple preclinical models of heart failure. However, the translational significance remains unclear. Human engineered heart tissues (EHTs) provide a means of quantifying the effects of chronic α1A-AR stimulation on human cardiomyocyte physiology. EHTs were created from thin slices of decellularized pig myocardium seeded with human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and fibroblasts. With a paired experimental design, EHTs were cultured for 3 wk, mechanically tested, cultured again for 2 wk with α1A-AR agonist A61603 (10 nM) or vehicle control, and retested after drug washout for 24 h. Separate control experiments determined the effects of EHT age (3-5 wk) or repeat mechanical testing. We found that chronic A61603 treatment caused a 25% increase of length-dependent activation (LDA) of contraction compared with vehicle treatment (n = 7/group, P = 0.035). EHT force was not increased after chronic A61603 treatment. However, after vehicle treatment, EHT force was increased by 35% relative to baseline testing (n = 7/group, P = 0.022), suggesting EHT maturation. Control experiments suggested that increased EHT force resulted from repeat mechanical testing, not from EHT aging. RNA-seq analysis confirmed that the α1A-AR is expressed in human EHTs and found chronic A61603 treatment affected gene expression in biological pathways known to be activated by α1A-ARs, including the MAP kinase signaling pathway. In conclusion, increased LDA in human EHT after chronic A61603 treatment raises the possibility that chronic stimulation of the α1A-AR might be beneficial for increasing LDA in human myocardium and might be beneficial for treating human heart failure by restoring LDA.NEW & NOTEWORTHY Chronic stimulation of α1A-adrenergic receptors (α1A-ARs) is known to mediate therapeutic effects in animal heart failure models. To investigate the effects of chronic α1A-AR stimulation in human cardiomyocytes, we tested engineered heart tissue (EHT) created with iPSC-derived cardiomyocytes. RNA-seq analysis confirmed human EHT expressed α1A-ARs. Chronic (2 wk) α1A-AR stimulation with A61603 (10 nM) increased length-dependent activation (LDA) of contraction. Chronic α1A-AR stimulation might be beneficial for treating human heart failure by restoring LDA.

First Dark Matter Search Results from the LUX-ZEPLIN (LZ) Experiment.

The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross sections for WIMP masses above 9 GeV/c^{2}. The most stringent limit is set for spin-independent scattering at 36 GeV/c^{2}, rejecting cross sections above 9.2×10^{-48} cm at the 90% confidence level.

[Psychiatric problems in people with hearing loss]. / Psychiatrische aandoeningen bij mensen met een gehoorbeperking.

BACKGROUND: Hearing loss means a reduced access to a spoken language, depending on the severity and the possibility of hearing support. A sign language is on the other hand fully accessible. AIM: To describe the impact of hearing loss on mental health related to language ability. METHOD: From the literature a general picture will be presented of the impact of hearing loss on mental health. This is followed by a discussion of the influence of hearing loss on the prevalence and influence of diverse psychiatric conditions (schizophrenia, autism, depression/anxiety disorders). RESULTS: A relationship between mental health problems and hearing loss is evidenced. The use of a sign language seems to reduce the risk of a mental health problem in deaf individuals. CONCLUSION: The results have to be interpreted alongside the fact that research is based on relatively few countries. It is therefore not possible to generalize the results; cultural differences possibly exist. The relationship between language choice and language ability has not been studied in enough depth. More research and comparative research across countries is essential with full information on language choice/language ability.

Colorectal cancer outcomes determined by mode of presentation: analysis of population data in England between 2010 and 2014.

BACKGROUND: The purpose of this study was to investigate associations between mode of presentation; categorized as emergency, suspected cancer outpatient referral pathway (2-week wait or 2WW pathway), non-cancer suspected outpatient referral (non-2-week wait pathway) or following screening, and stage of diagnosis and survival in patients with colorectal cancer in England. METHODS: This was a retrospective cohort observational study of patients diagnosed with colorectal cancer between January 2010 and December 2014 in England using data from Public Health England collated from regional cancer registries. RESULTS: The most common route to diagnosis among 167,501 patients diagnosed with colorectal cancer was via the non-cancer suspect (non-2WW) outpatient referral pathway (35.1%) followed by the suspected cancer (2WW) referral pathway (31.6%), emergency presentation (22.8%) and most infrequently following screening (10.6%) (p < 0.01). Screening confers the greatest likelihood of early-stage diagnosis (61.6%) compared to other modes of presentation. The 5-year overall survival was 81.8%, 53.3%, 53.0% and 27.6% in those diagnosed via screening, 2WW, non-2WW pathway and emergency presentation, respectively. Patients from most deprived regions were more likely to be diagnosed following emergency presentation (27.7 vs 19.7%, p < 0.01) and less likely via screening (8.1 vs 12%, p < 0.01). CONCLUSIONS: Asymptomatic individuals diagnosed following screening have earlier stage cancers and better survival, the opposite was observed in those diagnosed following emergency presentation. Patients referred via the 2WW pathway do not have better survival outcomes when compared to those referred via the non-2WW pathway. In addition, this study has identified socio-economic groups that need to be targeted with public health campaigns to improve screening uptake.

Bronchiectasis is associated with delayed diagnosis and adverse outcomes in the New Zealand Common Variable Immunodeficiency Disorders cohort study.

Common variable immunodeficiency disorders (CVID) are multi-system disorders where target organ damage is mediated by infective, autoimmune and inflammatory processes. Bronchiectasis is probably the most common disabling complication of CVID. The risk factors for bronchiectasis in CVID patients are incompletely understood. The New Zealand CVID study (NZCS) is a nationwide longitudinal observational study of adults, which commenced in 2006. In this analysis, the prevalence and risk factors for bronchiectasis were examined in the NZCS. After informed consent, clinical and demographic data were obtained with an interviewer-assisted questionnaire. Linked electronic clinical records and laboratory results were also reviewed. Statistical methods were applied to determine if variables such as early-onset disease, delay in diagnosis and increased numbers of infections were associated with greater risk of bronchiectasis. One hundred and seven adult patients with a diagnosis of CVID are currently enrolled in the NZCS, comprising approximately 70% of patients known to have CVID in New Zealand. Fifty patients (46·7%) had radiologically proven bronchiectasis. This study has shown that patients with compared to those without bronchiectasis have an increased mortality at a younger age. CVID patients with bronchiectasis had a greater number of severe infections consequent to early-onset disease and delayed diagnosis. Indigenous Maori have a high prevalence of CVID and a much greater burden of bronchiectasis compared to New Zealand Europeans. Diagnostic latency has not improved during the study period. Exposure to large numbers of infections because of early-onset disease and delayed diagnosis was associated with an increased risk of bronchiectasis. Earlier diagnosis and treatment of CVID may reduce the risk of bronchiectasis and premature death in some patients.

The rapid assembly of an elliptical galaxy of 400 billion solar masses at a redshift of 2.3.

Stellar archaeology shows that massive elliptical galaxies formed rapidly about ten billion years ago with star-formation rates of above several hundred solar masses per year. Their progenitors are probably the submillimetre bright galaxies at redshifts z greater than 2. Although the mean molecular gas mass (5 × 10(10) solar masses) of the submillimetre bright galaxies can explain the formation of typical elliptical galaxies, it is inadequate to form elliptical galaxies that already have stellar masses above 2 × 10(11) solar masses at z ≈ 2. Here we report multi-wavelength high-resolution observations of a rare merger of two massive submillimetre bright galaxies at z = 2.3. The system is seen to be forming stars at a rate of 2,000 solar masses per year. The star-formation efficiency is an order of magnitude greater than that of normal galaxies, so the gas reservoir will be exhausted and star formation will be quenched in only around 200 million years. At a projected separation of 19 kiloparsecs, the two massive starbursts are about to merge and form a passive elliptical galaxy with a stellar mass of about 4 × 10(11) solar masses. We conclude that gas-rich major galaxy mergers with intense star formation can form the most massive elliptical galaxies by z ≈ 1.5.

Response and place learning in crayfish spatial behavior.

Previous studies have demonstrated that animals use both environmental cues and egocentric information when orienting in mazes or nature. These two strategies have been examined separately in some species, yielding information on the specific properties associated with each. We examined spatial learning in crayfish (Orconectes rusticus) using an apparatus that required animals to orient under four different conditions: using egocentric (response) cues alone, response cues with inconsistent external (place) cues present, place cues with inconsistent response cues present, and place cues with consistent response cues present. Results demonstrated that crayfish could successfully learn a maze task using response cues alone and when external visual and tactile cues provided inconsistent information. Animals were markedly less successful at learning the task using place cues while disregarding inconsistent response information. We also found that more animals learned successfully when response and external cues were presented in a redundant format where both cues indicated the correct turn. Finally, we found that some crayfish were able to learn a single reversal when trained using response information alone and when response and external cues were presented in the redundant format. We consider these results in the light of findings from other species, and ideas on learning strategy properties, ecological relevance of strategies, and the possible role of stress coping style in crayfish learning.

Dilution and microfiltration of particulate corticosteroids for spinal epidural injections: impact on drug concentration and agglomerate formation.

Particulate corticosteroids have been described to lead to greater pain improvement compared with their non-particulate counterparts when used in epidural injections. It is hypothesised that filtering may significantly impact their concentration and long-term efficacy. We investigated if passing particulate suspensions through different commonly-used filters affects drug dosage. Two particulate corticosteroid formulations, triamcinolone acetonide and methylprednisolone acetate, were mixed at different concentrations with either bupivacaine hydrochloride or 0.9% sodium chloride. Solutions were passed through a 5-µm and a 0.2-µm filter. Mass spectroscopy results indicated a complete loss of corticosteroid from the solutions using both filters, and light microscopy imaging demonstrated agglomerate formation, suggesting that filtering interferes with drug dosage. The choice of diluents must also be considered to reduce large agglomerate formation. Clinicians should be aware of the consequences of filtering particulate suspensions and carefully consider the selection of diluent when considering treatment plans.

'Summer of Sport': the development of a 6-week programme in increasing physical activity to improve public health outcomes.

OBJECTIVES: A population-based physical activity (PA) programme was implemented to increase PA levels and encourage individuals to join the local council leisure facility. STUDY DESIGN: This is a cross-sectional design. METHODS: The 6-week programme Summer of Sport (SOS) involved a total of 487 individuals registered for PA sessions. The sessions were held at three local council leisure facilities included badminton, swimming, table tennis, squash and group cycle. The programme was assessed using a survey based on the Theory of Planned Behaviour. Individuals were asked for their current fitness levels, whether the programme encouraged them to be more active and for their intentions to join the leisure centre after the programme. RESULTS: Of the 487 who originally registered for the programme, there were 161 users of SOS, with 112 not already members of the leisure facility. After the programme, 83% considered themselves already being active, with 78% stating that they partook in at least 30 min of exercise, 3 times per week. Although a large proportion of individuals were already physically active, 78% stated that taking part encouraged them to become more active. More than half suggested that they would not join the leisure facility, 30% said that they had joined after the programme and 17% stated their intention to join. Many individuals highlighted that the programme provided an opportunity to be active with their family. CONCLUSIONS: Public health teams should work with partner organisations to embed robust processes for measuring outcomes that impact on population health.

In situ study of sigma phase formation in Cr-Co-Ni ternary alloys at 800°C using the long duration experiment facility at Diamond Light Source.

The new long duration experiment facility on beamline I11 at Diamond Light Source has been used to study the kinetics of sigma phase formation in three Cr-Co-Ni alloys. Diffraction data acquired during in situ exposure at 800°C for 50 d showed progressive increases in the sigma fraction. This was accompanied by changes in the proportions of the other phases, which differed markedly between the alloys studied. These results demonstrate the capabilities of the long duration facility for the study of metallurgical phenomena over periods of months to years, a capability not previously available at a synchrotron source.

Does human endometrial LGR5 gene expression suggest the existence of another hormonally regulated epithelial stem cell niche?

STUDY QUESTION: Is human endometrial leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) gene expression limited to the postulated epithelial stem cell niche, stratum basalis glands, and is it hormonally regulated? SUMMARY ANSWER: LGR5 expressing cells are not limited to the postulated stem cell niche but LGR5 expression is hormonally regulated. WHAT IS KNOWN ALREADY: The human endometrium is a highly regenerative tissue; however, endometrial epithelial stem cell markers are yet to be confirmed. LGR5 is a marker of stem cells in various epithelia. STUDY DESIGN, SIZE, DURATION: The study was conducted at a University Research Institute. Endometrial samples from 50 healthy women undergoing benign gynaecological surgery with no endometrial pathology at the Liverpool Women's hospital were included and analysed in the following six sub-categories; proliferative, secretory phases of menstrual cycle, postmenopausal, those using oral and local progestagens and samples for in vitro explant culture. PARTICIPANTS/MATERIALS, SETTING, METHODS: In this study, we used the gold standard method, in situ hybridisation (ISH) along with qPCR and a systems biology approach to study the location of LGR5 gene expression in full thickness human endometrium and Fallopian tubes. The progesterone regulation of endometrial LGR5 was examined in vivo and in short-term cultured endometrial tissue explants in vitro. LGR5 expression was correlated with epithelial proliferation (Ki67), and expression of previously reported epithelia progenitor markers (SOX9 and SSEA-1) immunohistochemistry (IHC). MAIN RESULTS AND THE ROLE OF CHANCE: LGR5 gene expression was significantly higher in the endometrial luminal epithelium than in all other epithelial compartments in the healthy human endometrium, including the endometrial stratum basalis (P < 0.05). The strongest SSEA-1 and SOX9 staining was observed in the stratum basalis glands, but the general trend of SOX9 and SSEA-1 expression followed the same cyclical pattern of expression as LGR5. Stratum functionalis epithelial Ki67-LI and LGR5 expression levels correlated significantly (r = 0.74, P = 0.01), however, they did not correlate in luminal and stratum basalis epithelium (r = 0.5 and 0.13, respectively). Endometrial LGR5 demonstrates a dynamic spatiotemporal expression pattern, suggesting hormonal regulation. Oral and local progestogens significantly reduced endometrial LGR5 mRNA levels compared with women not on hormonal treatment (P < 0.01). Our data were in agreement with in silico analysis of published endometrial microarrays. LARGE SCALE DATA: We did not generate our own large scale data but interrogated publically available large scale data sets. LIMITATIONS, REASONS FOR CAUTION: In the absence of reliable antibodies for human LGR5 protein and validated lineage markers for the various epithelial populations that potentially exist within the endometrium, our study does not formally characterise or examine the functional ability of the resident LGR5+ cells as multipotent. WIDER IMPLICATIONS OF THE FINDINGS: These data will facilitate future lineage tracing studies in the human endometrial epithelium; to identify the location of stem cells and further complement the in vitro functional studies, to confirm if the LGR5 expressing epithelial cells indeed represent the epithelial stem cell population. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by funding from the Wellbeing of Women project grant (RTF510) and Cancer Research UK (A14895). None of the authors have any conflicts of interest to disclose.

Acute West Nile Virus Meningoencephalitis Diagnosed Via Metagenomic Deep Sequencing of Cerebrospinal Fluid in a Renal Transplant Patient.

Solid organ transplant patients are vulnerable to suffering neurologic complications from a wide array of viral infections and can be sentinels in the population who are first to get serious complications from emerging infections like the recent waves of arboviruses, including West Nile virus, Chikungunya virus, Zika virus, and Dengue virus. The diverse and rapidly changing landscape of possible causes of viral encephalitis poses great challenges for traditional candidate-based infectious disease diagnostics that already fail to identify a causative pathogen in approximately 50% of encephalitis cases. We present the case of a 14-year-old girl on immunosuppression for a renal transplant who presented with acute meningoencephalitis. Traditional diagnostics failed to identify an etiology. RNA extracted from her cerebrospinal fluid was subjected to unbiased metagenomic deep sequencing, enhanced with the use of a Cas9-based technique for host depletion. This analysis identified West Nile virus (WNV). Convalescent serum serologies subsequently confirmed WNV seroconversion. These results support a clear clinical role for metagenomic deep sequencing in the setting of suspected viral encephalitis, especially in the context of the high-risk transplant patient population.

Assessing Adherence to Antihypertensive Therapy in Primary Health Care in Namibia: Findings and Implications.

INTRODUCTION: Namibia has the highest burden and incidence of hypertension in sub-Sahara Africa. Though non-adherence to antihypertensive therapy is an important cardiovascular risk factor, little is known about potential ways to improve adherence in Namibia following universal access. The objective of this study is to validate the Hill-Bone compliance scale and determine the level and predictors of adherence to antihypertensive treatment in primary health care settings in sub-urban townships of Windhoek, Namibia. METHODS: Reliability was determined by Cronbach's alpha. Principal component analysis (PCA) was used to assess construct validity. RESULTS: The PCA was consistent with the three constructs for 12 items, explaining 24.1, 16.7 and 10.8% of the variance. Cronbach's alpha was 0.695. None of the 120 patients had perfect adherence to antihypertensive therapy, and less than half had acceptable levels of adherence (≥ 80%). The mean adherence level was 76.7 ± 8.1%. Three quarters of patients ever missed their scheduled clinic appointment. Having a family support system (OR = 5.4, 95% CI 1.687-27.6, p = 0.045) and attendance of follow-up visits (OR = 3.1, 95% CI 1.1-8.7, p = 0.03) were significant predictors of adherence. Having HIV/AIDs did not lower adherence. CONCLUSIONS: The modified Namibian version of the Hill-Bone scale is reliable and valid for assessing adherence to antihypertensives in Namibia. There is sub-optimal adherence to antihypertensive therapy among primary health cares in Namibia. This needs standardized systems to strengthen adherence monitoring as well as investigation of other factors including transport to take full advantage of universal access.

Heads Up: a pilot trial of a psychological intervention to improve nutrition in head and neck cancer patients undergoing radiotherapy.

Malnutrition in head and neck cancer (HNC) patients is common and associated with poorer radiotherapy outcomes including increased mortality. This pilot trial investigates the feasibility and effectiveness of a psychological intervention to improve nutritional status, depression and mortality in HNC patients undergoing radiotherapy. Fifty-nine intervention patients received motivational interviewing and cognitive behavioural therapy compared to 70 historical controls who received treatment as usual. Participants were assessed for nutrition, depression and mortality. There were no significant differences between groups in nutritional status, depression or mortality. Subgroup analyses among patients at greater nutritional risk (cancers of the oral cavity, pharynx, larynx) revealed a potentially clinically important reduction on the PG-SGA and lower mortality (31% of controls vs. 16% intervention; P = 0.03) in favour of the intervention condition. Potential benefits in nutritional status and in mortality in this pilot trial of a psychological intervention among HNC patients at high nutritional risk suggest that a larger randomised controlled trial is warranted.

Comparison of clinical and radiographic status around immediately loaded versus conventional loaded implants placed in patients with type 2 diabetes: 12- and 24-month follow-up results.

There are no studies that have compared the clinical and radiographic status around immediately loaded (IL) and conventional loaded (CL) implants placed in patients with type 2 diabetes mellitus (T2DM). The aim was to compare the clinical and radiographic status around IL and CL implants placed in T2DM patients. One hundred and eight diabetic patients [55 with IL implants (Group 1) and 53 with CL implants (Group 2)] were included in this cross-sectional study. All implants were placed in healed sites in the maxillary and mandibular premolar and molar regions and supported single restorations. All patients underwent full mouth mechanical debridement biannually. Haemoglobin A1c (HbA1c) levels, clinical [bleeding on probing (BOP) and probing depth (PD) ≥ 4 mm] and radiographic [crestal bone loss (CBL)] peri-implant parameters were measured for both groups at 12- and 24-month follow-up. Group comparisons were performed using the Mann-Whitney U-test (P < 0·05). The mean age and duration of T2DM in groups 1 and 2 were 50·6 ± 2·2 and 51·8 ± 1·7 years, and 9·2 ± 2·4 and 8·5 ± 0·4 years, respectively. At 12- and 24-month follow-up, the mean HbA1c levels in groups 1 and 2 were 5·4% (4·8-5·5%) and 5·1% (4·7-5·4%) and 5·1% (4·7-5·2%) and 4·9% (4·5-5·2%), respectively. At 12- and 24-month follow-up, there was no statistically significant difference in peri-implant BOP, PD and CBL in both groups. It was concluded that clinical and radiographic status is comparable around IL and CL implants placed in patients with T2DM. The contribution of careful case selection, oral hygiene maintenance and glycaemic control is emphasised.

The relevance of coagulation factor X protection of adenoviruses in human sera.

Intravenous delivery of adenoviruses is the optimal route for many gene therapy applications. Once in the blood, coagulation factor X (FX) binds to the adenovirus capsid and protects the virion from natural antibody and classical complement-mediated neutralisation in mice. However, to date, no studies have examined the relevance of this FX/viral immune protective mechanism in human samples. In this study, we assessed the effects of blocking FX on adenovirus type 5 (Ad5) activity in the presence of human serum. FX prevented human IgM binding directly to the virus. In individual human sera samples (n=25), approximately half of those screened inhibited adenovirus transduction only when the Ad5-FX interaction was blocked, demonstrating that FX protected the virus from neutralising components in a large proportion of human sera. In contrast, the remainder of sera tested had no inhibitory effects on Ad5 transduction and FX armament was not required for effective gene transfer. In human sera in which FX had a protective role, Ad5 induced lower levels of complement activation in the presence of FX. We therefore demonstrate for the first time the importance of Ad-FX protection in human samples and highlight subject variability and species-specific differences as key considerations for adenoviral gene therapy.