Empowering Women Researchers in the New Century: IADR's Strategic Direction.

Gender inequality in science, medicine, and dentistry remains a central concern for the biomedical research workforce today. Although progress in areas of inclusivity and gender diversity was reported, growth has been slow. Women still face multiple challenges in reaching higher ranks and leadership positions while maintaining holistic success in these fields. Within dental research and academia, we might observe trends toward a more balanced pipeline. However, women continue to face barriers in seeking leadership roles and achieving economic equity and scholarship recognition. In an effort to evaluate the status of women in dental research and academia, the authors examined the role of the International Association for Dental Research (IADR), a global research organization, which has improved awareness on gender inequality. The goal of this article is to review five crucial issues of gender inequality in oral health research and academics-workforce pipeline, economic inequality, workplace harassment, gender bias in scholarly productivity, and work-life balance-and to discuss proactive steps that the IADR has taken to promote gender equality. Providing networking and training opportunities through effective mentoring and coaching for women researchers, the IADR has developed a robust pipeline of women leaders while promoting gender equality for women in dental academia through a culture shift. As knowledge gaps remained on the levels of conscious and unconscious bias and sexist culture affecting women advancement in academics, as well as the intersectionality of gender with race, gender identity, ability status, sexual orientation, and cultural backgrounds, the IADR has recognized that further research is warranted.

Study of the use of antidepressants for depression in dementia: the HTA-SADD trial--a multicentre, randomised, double-blind, placebo-controlled trial of the clinical effectiveness and cost-effectiveness of sertraline and mirtazapine.

OBJECTIVE: Depression is common in dementia, causing considerable distress and other negative impacts. Treating it is a clinical priority, but the evidence base is sparse and equivocal. This trial aimed to determine clinical effectiveness of sertraline and mirtazapine in reducing depression 13 weeks post randomisation compared with placebo. DESIGN: Multicentre, parallel-group, double-blind placebo-controlled randomised controlled trial of the clinical effectiveness of sertraline and mirtazapine with 13- and 39-week follow-up. SETTING: Nine English old-age psychiatry services. PARTICIPANTS: A pragmatic trial. Eligibility: probable or possible Alzheimer's disease (AD), depression (4+ weeks) and Cornell Scale for Depression in Dementia (CSDD) score of 8+. EXCLUSIONS: clinically too critical (e.g. suicide risk); contraindication to medication; taking antidepressants; in another trial; and having no carer. INTERVENTIONS: (1) Sertraline; (2) mirtazapine; and (3) placebo, all with normal care. Target doses: 150 mg of sertraline or 45 mg of mirtazapine daily. OUTCOME: CSDD score. Randomisation: Allocated 1 : 1 : 1 through Trials Unit, independently of trial team. Stratified block randomisation by centre, with randomly varying block sizes; computer-generated randomisation. Blinding: Double blind: medication and placebo identical for each antidepressant. Referring clinicians, research workers, participants and pharmacies were blind. Statisticians blind until analyses completed. RESULTS: Numbers randomised: 326 participants randomised (111 placebo, 107 sertraline and 108 mirtazapine). OUTCOME: Differences in CSDD at 13 weeks from an adjusted linear-mixed model: mean difference (95% CI) placebo-sertraline 1.17 (-0.23 to 2.78; p = 0.102); placebo-mirtazapine 0.01 (-1.37 to 1.38; p = 0.991); and mirtazapine-sertraline 1.16 (-0.27 to 2.60; p = 0.112). HARMS: Placebo group had fewer adverse reactions (29/111, 26%) than sertraline (46/107, 43%) or mirtazapine (44/108, 41%; p = 0.017); 39-week mortality equal, five deaths in each group. CONCLUSIONS: This is a trial with negative findings but important clinical implications. The data suggest that the antidepressants tested, given with normal care, are not clinically effective (compared with placebo) for clinically significant depression in AD. This implies a need to change current practice of antidepressants being the first-line treatment of depression in AD. From the data generated we formulated the following recommendations for future work. (1) The secondary analyses presented here suggest that there would be value in carrying out a placebo-controlled trial of the clinical effectiveness and cost-effectiveness of mirtazapine in the management of Behavioural and Psychological Symptoms of Dementia. (2) A conclusion from this study is that it remains both ethical and essential for trials of new medication for depression in dementia to have a placebo arm. (3) Further research is required to evaluate the impact that treatments for depression in people with dementia can have on their carers not only in terms of any impacts on their quality of life, but also the time they spend care-giving. (4) There is a need for research into alternative biological and psychological therapies for depression in dementia. These could include evaluations of new classes of antidepressants (such as venlafaxine) or antidementia medication (e.g. cholinesterase inhibitors). (5) Research is needed to investigate the natural history of depression in dementia in the community when patients are not referred to secondary care services. (6) Further work is needed to investigate the cost modelling results in this rich data set, investigating carer burden and possible moderators to the treatment effects. (7) There is scope for reanalysis of the primary outcome in terms of carer and participant CSDD results.

Palaeogenetic evidence supports a dual model of Neolithic spreading into Europe.

The peopling of Europe is a complex process. One of the most dramatic demographic events, the Neolithic agricultural revolution, took place in the Near East roughly 10000 years ago and then spread through the European continent. Nevertheless, the nature of this process (either cultural or demographic) is still a matter of debate among scientists. We have retrieved HVRI mitochondrial DNA sequences from 11 Neolithic remains from Granollers (Catalonia, northeast Spain) dated to 5500 years BP. We followed the proposed authenticity criteria, and we were also able, for the first time, to track down the pre-laboratory-derived contaminant sequences and consequently eliminate them from the generated cloning dataset. Phylogeographic analysis shows that the haplogroup composition of the Neolithic population is very similar to that found in modern populations from the Iberian Peninsula, suggesting a long-time genetic continuity, at least since Neolithic times. This result contrasts with that recently found in a Neolithic population from Central Europe and, therefore, raises new questions on the heterogeneity of the Neolithic dispersals into Europe. We propose here a dual model of Neolithic spread: acculturation in Central Europe and demic diffusion in southern Europe.

The genetics of the pre-Roman Iberian Peninsula: a mtDNA study of ancient Iberians.

The Iberians developed a surprisingly sophisticated culture in the Mediterranean coast of the Iberian Peninsula from the 6th century BC until their conquest by the Romans in the 2nd century BC. They spoke and wrote a non-Indo-European language that still cannot be understood; their origins and relationships with other non-Indo-European peoples, like the Etruscans, are unclear, since their funerary practices were based on the cremation of bodies, and therefore anthropology has been unable to approach the study of this people. We have retrieved mitochondrial DNA (mtDNA) from a few of the scarce skeletal remains that have been preserved, some of them belonging to ritualistically executed individuals. The most stringent authentication criteria proposed for ancient DNA, such as independent replication, amino-acid analysis, quantitation of template molecules, multiple extractions and cloning of PCR products, have been followed to obtain reliable sequences from the mtDNA hypervariable region 1 (HVR1), as well as some haplogroup diagnostic SNPs. Phylogeographic analyses show that the haplogroup composition of the ancient Iberians was very similar to that found in modern Iberian Peninsula populations, suggesting a long-term genetic continuity since pre-Roman times. Nonetheless, there is less genetic diversity in the ancient Iberians than is found among modern populations, a fact that could reflect the small population size at the origin of the population sampled, and the heterogenic tribal structure of the Iberian society. Moreover, the Iberians were not especially closely related to the Etruscans, which points to considerable genetic heterogeneity in Pre-Roman Western Europe.

Unravelling migrations in the steppe: mitochondrial DNA sequences from ancient central Asians.

This study helps to clarify the debate on the Western and Eastern genetic influences in Central Asia. Thirty-six skeletal remains from Kazakhstan (Central Asia), excavated from different sites dating between the fifteenth century BC to the fifth century AD, have been analysed for the hypervariable control region (HVR-I) and haplogroup diagnostic single nucleotide polymorphisms (SNPs) of the mitochondrial DNA genome. Standard authentication criteria for ancient DNA studies, including multiple extractions, cloning of PCR products and independent replication, have been followed. The distribution of east and west Eurasian lineages through time in the region is concordant with the available archaeological information: prior to the thirteenth-seventh century BC, all Kazakh samples belong to European lineages; while later an arrival of east Eurasian sequences that coexisted with the previous west Eurasian genetic substratum can be detected. The presence of an ancient genetic substratum of European origin in West Asia may be related to the discovery of ancient mummies with European features in Xinjiang and to the existence of an extinct Indo-European language, Tocharian. This study demonstrates the usefulness of the ancient DNA in unravelling complex patterns of past human migrations so as to help decipher the origin of present-day admixed populations.

Mitochondrial DNA from pre-Columbian Ciboneys from Cuba and the prehistoric colonization of the Caribbean.

To assess the genetic affinities of extinct Ciboneys (also called Guanajuatabeys) from Cuba, 47 pre-Columbian skeletal samples belonging to this group were analyzed using ancient DNA techniques. At the time of European contact, the center and east of Cuba were occupied by agriculturalist Taino groups, while the west was mainly inhabited by Ciboneys, hunter-gatherers who have traditionally been considered a relic population descending from the initial colonization of the Caribbean. The mtDNA hypervariable region I (HVR-I) and haplogroup-specific markers were amplified and sequenced in 15 specimens using overlapping fragments; amplification from second extractions from the same sample, independent replication in different laboratories, and cloning of some PCR products support the authenticity of the sequences. Three of the five major mtDNA Amerindian lineages (A, C, and D) are present in the sample analyzed, in frequencies of 0.07, 0.60, and 0.33, respectively. Different phylogenetic analyses seem to suggest that the Caribbean most likely was populated from South America, although the data are still inconclusive, and Central American influences cannot be discarded. Our hypothesis is that the colonization of the Caribbean mainly took place in successive migration movements that emanated from the same area in South America, around the Lower Orinoco Valley: the first wave consisted of hunter-gatherer groups (ancestors of the Ciboneys), a subsequent wave of agriculturalists (ancestors of the Tainos), and a latter one of nomadic Carib warriors. However, further genetic studies are needed to confirm this scenario.

Phytic acid (IP6), novel broad spectrum anti-neoplastic agent: a systematic review.

INTRODUCTION: Phytic acid or IP6 has been extensively studied in animals and is being promoted as an anti-cancer agent in health food stores. It is naturally found in legumes, wheat bran, and soy foods. It is believed to be the active ingredient that gives these substances their cancer fighting abilities. Proposed mechanisms of action include gene alteration, enhanced immunity, and anti-oxidant properties. METHODS: A Medline search from 1966 to May 2002 using the keywords phytic acid and cancer, and limiting the search to the subheadings of therapeutic uses, prevention, and adverse effects revealed 28 studies. These studies were included in the review. RESULTS: A great majority of the studies were done in animals and showed that phytic acid had anti-neoplastic properties in breast, colon, liver, leukemia, prostate, sarcomas, and skin cancer. There were no human studies. Side effects included chelation of multivalent cations, and an increase in bladder and renal papillomas. This increase in papilloma formation only occurred with the sodium salt of phytic acid. It did not occur with either the potassium or magnesium salts. CONCLUSIONS: There is a large body of animal evidence to show that phytic acid may have a role in both the prevention and treatment of many forms of cancer. There is clearly enough evidence to justify the initiation of Phase I and Phase II clinical trials in humans.

Short-cycle structured intermittent treatment of chronic HIV infection with highly active antiretroviral therapy: effects on virologic, immunologic, and toxicity parameters.

Although continuous highly active antiretroviral therapy (HAART) is effective for many HIV-infected patients, it can be toxic and prohibitive in cost. By decreasing the total amount of time patients receive medications, intermittent HAART could reduce toxicity and cost. Therefore, we initiated a pilot study in which 10 HIV-infected individuals receiving effective therapy that resulted in levels of HIV RNA <50 copies per ml of plasma and CD4(+) T cell counts >300 cells per mm(3) of whole blood received repeated cycles of 7 days on HAART followed by 7 days off of HAART. Patients maintained suppression of plasma viremia for 32-68 weeks. There was no significant increase in HIV proviral DNA or replication-competent HIV in peripheral CD4(+) T cells or HIV RNA in peripheral blood or lymph node mononuclear cells. There was no significant change in CD4(+) T cell counts, no significant increase in CD4(+) or CD8(+) T cells expressing activation markers or producing IFN-gamma in response to HIV, no increase in CD4(+) T cell proliferation to p24 antigen, and no evidence for the development of resistance to HAART medications. There was a significant decrease in serum cholesterol and triglyceride levels. Thus, in this proof-of-concept study, short-cycle intermittent HAART maintained suppression of plasma viremia as well as HIV replication in reservoir sites while preserving CD4(+) T cell counts. In addition, there was a decrease in serum cholesterol and triglyceride levels. Intermittent therapy may be an important strategy to reduce cost and toxicity for HIV-infected individuals.

Measurement of in situ hybridization.

Hybridization of labeled specific molecular probes to nucleic acids in tissues allows geometric and functional location of gene expression or of foreign genome sequences. Estimates of amounts and location of target nucleic acid sequence can be made with phosphor storage imaging and molecular controls.

Magnesium: its proven and potential clinical significance.

Magnesium is the fourth most abundant cation in the body and is present in more than 300 enzymatic systems, where it is crucial for adenosine triphosphate (ATP) metabolism. Deficiency states result in increased insulin resistance, as well as increased smooth muscle and platelet reactivity. Magnesium deficiency has been shown to correlate with a number of chronic cardiovascular diseases, including hypertension, diabetes mellitus, and hyperlipidemia. Intravenous magnesium has been used therapeutically in critical situations such as status asthmaticus, torsades de pointes, and preeclampsia. Few controlled studies exist regarding the therapeutic uses of oral magnesium supplementation in chronic cardiovascular diseases. Randomized clinical trials are urgently needed to determine whether magnesium supplementation will alter the natural history of these disease states.

The effects of guided imagery on comfort of women with early stage breast cancer undergoing radiation therapy.

PURPOSE/OBJECTIVES: To measure the effectiveness of customized guided imagery for increasing comfort in women with early stage breast cancer. DESIGN: Experimental longitudinal, random assignment to groups. SETTING: Two urban radiation oncology departments. SAMPLE: 53 women (26 in the experimental group, 27 in the control group) aged 37-81; 80% European and 10% African American with stage I or II breast cancer about to begin radiation therapy. METHODS: The experimental group was to listen to a guided imagery audiotape once a day for the duration of the study. The Radiation Therapy Comfort Questionnaire was self-administered at three time points: prior to the introduction of intervention and the beginning of radiation therapy (Time 1), three weeks later (Time 2), and three weeks after completing radiation therapy (Time 3). The State Anxiety Inventory was administered at Time 1 only. MAIN RESEARCH VARIABLES: The effect of use of guided imagery on comfort with anxiety as a control variable. FINDINGS: Pooled data indicated a significant overall increase in differences in comfort between the treatment and control group, with the treatment group having higher comfort over time. The data also revealed a significant linear trend in differences between groups. No significant interaction of group and time existed. CONCLUSIONS: Guided imagery is an effective intervention for enhancing comfort of women undergoing radiation therapy for early stage breast cancer. The intervention was especially salient in the first three weeks of therapy. IMPLICATIONS FOR NURSING PRACTICE: Guided imagery audiotapes specifically designed for this population were resource effective in terms of cost, personnel, and time.

Cranial variation in the Iberian Peninsula and the Balearic Islands: inferences about the history of the population.

A multivariate analysis of four prehistoric and nine historic populations from the Iberian Peninsula and Balearic Islands with large sample sizes (n > 30 individuals for the neurocranium and n > 15 for the facial skeleton) is presented, considering 874 male and 557 female skulls and using 20 craniometric measurements. Cluster analyses have been undertaken using the squared Euclidean distance as a measure of proximity and the average linkage between groups (UPGMA), and neighbor-joining algorithms as a branching method, and a bootstrap analysis was used to assess the robustness of the clustering topology. The study was complemented with a principal coordinate analysis and with the application of the Mantel test to measure the degree of correspondence between the information furnished by the female and the male samples. The analyses show that the main source of morphometric variability in the Iberian Peninsula is the Basque population. The second source of variation is provided by two populations (Muslims and Jews), different from the rest from an archaeological and cultural point of view, and can probably be attributed to influences from sub-Saharan Africa. The massive deportations of the Jews in 1492 and of the Moors between the 15th and 17th centuries may have erased this source of variability from the present population of the Iberian Peninsula. The remaining studied populations, including samples from Castile, Cantabria, Andalusia, Catalonia and Balearic Islands, are grouped together, showing a notable morphological homogeneity, despite their temporal and geographic heterogeneity. These results are in general agreement with those obtained in synthetic maps, by analyzing multiple genetic markers. In such studies, the Basque population is described as the main source of genetic variability, not only in the Iberian Peninsula, but also in Western Europe.

Comparative evaluation of zinc sulfadiazine and silver sulfadiazine in burn wound infection.

One percent silver sulfadiazine has been commonly used as a topical antimicrobial agent after a burn injury. Incidence of burn wound colonization by Staphylococcus aureus in patients treated with silver sulfadiazine has spurred research for other agents. A topical preparation that contains zinc and sulfadiazine (Zad-G) was evaluated for in vitro antibacterial spectrum and in vivo efficacy. Muscle biopsy specimens of rats treated with Zad-G appear to have fewer colonies of S. aureus than groups treated with silver sulfadiazine. Topical therapy with Zad-G for patients with burns was comfortable, reduced wound infection, and was comparable to therapy with silver sulfadiazine. A topical Zad-G preparation that contains zinc sulfadiazine appears to be an effective alternative to silver sulfadiazine in the treatment of burn wounds.

Chylous cyst of the transverse colon.

A patient, who proved to have a chylous cyst of the colon, presented with bright red rectal bleeding and an abnormality on barium enema suggesting a colonic polyp. We review such an unusual presentation and other reported cases.

Norfloxacin and silver norfloxacin in the treatment of Pseudomonas corneal ulcer in the rabbit.

Norfloxacin is a new synthetic antibiotic with a broad spectrum of activity against gram-positive and gram-negative bacteria, and is more effective than the aminoglycosides against P aeruginosa. In this study norfloxacin was particularly effective in treatment of P aeruginosa infection of the rabbit cornea, and caused no toxicity in normal rabbit eyes after prolonged administration. The addition of silver to norfloxacin enhances its antipseudomonal activity, and broadens its spectrum to include antifungal activity. In this study, silver norfloxacin appears to be the most effective antibiotic against P aeruginosa corneal ulcer in the rabbit. Because of its broad antibacterial spectrum, silver norfloxacin may be useful in the initial treatment of bacterial corneal ulcer before the identity of the bacteria is known. Because of its low toxicity in topical administration, and its antifungal and antibacterial activity, silver norfloxacin may be helpful in prophylaxis against infection in chronic corneal ulcers.

Metal sulfonamides as antibacterial agents in topical therapy.

The apparent efficacy of zinc and cerium sulfadiazine and the metabolic role of other trace metals suggested that sulfonamide salts of these might be of therapeutic value. There is also a possibility that metal salts of other sulfonamides might be useful. Accordingly other sulfonamide salts of zinc were prepared and studied in vitro and in vivo. Only zinc sulfathiazole and zinc methoxazole were as effective as zinc sulfadiazine in animal studies. The sulfadiazines of aluminum, chromium, cobalt, copper and iron were prepared and compared in vitro and in vivo. Only cobalt sulfadiazine appeared comparable to zinc and cerium sulfadiazine in healing burn wounds in rats. Studies on the molecular structure of silver sulfonamides disclosed the polymeric structure peculiar to silver sulfadiazine which appears to account for its unique properties. It is not yet known whether other metal sulfadiazines have this attribute.

A comparison of three methods for predicting hearing loss from acoustic reflex thresholds.

Previously reported acoustic reflex threshold data from normal and hearing-impaired subjects indicate that the effect of stimulus bandwidth on reflex thresholds is altered by sensorineural hearing loss. It is this change in the "bandwidth effect" that forms the basis for predicting hearing loss from reflex threshold data. Three predictive procedures were compared for 17 normal and 60 hearing-impaired ears. All methods correctly identified most hearing losses but none of the methods accurately estimated magnitude of hearing loss. Two methods were characterized by a high rate of false positives. The third was tailored to minimize false positives (6%) and maintain a high rate (93%) of predicting hearing losses greater than 32 dB while making no attempt to make finer discriminations. This more conservative approach minimizes serious predictive errors while identifying a high proportion of clinically significant hearing losses.