Efficacy and Safety of an Ophthalmic DMPC-Based Nanoemulsion in Patients with Dry Eye Disease: A Phase I/II Randomized Clinical Trial.

Purpose: The goals of this study were to evaluate the safety and efficacy of an ophthalmic 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-based nanoemulsion (Nanodrop®) in patients with dry eye disease (DED). Methods: This was a randomized phase I/II multicentric, prospective, double-blind clinical trial. Patients (phase I: n = 25 and phase II: n = 101) were assigned to receive either PRO-176 (Nanodrop®) or Systane Balance® (control) for 29 days. Once the visits of the first 25 subjects were completed, if there were less than 20% of unexpected adverse events (AEs), related to PRO-176, recruitment was continued until the sample was completed for noninferiority (efficacy) analysis (phase II, n = 126). Efficacy endpoints were the ocular surface disease index (OSDI), tear break-up time (TBUT), epithelial defects, best corrected visual acuity (BCVA), and the incidence of expected AE. Results: For the phase I portion of the study, there were no differences between groups regarding the incidence of AE. All related-AE symptoms in both groups were mild and expected. For the phase II subset, there was a significant reduction in OSDI scores at day 29 and noninferiority between treatments was confirmed (p=0.650, CI 95% [-8.7, 5.5]). Similar improvement was observed for TBUT although no significant intergroup differences were found (p=0.518, CI 95% [-0.08, 1.6]). There were no significant differences between treatments for epithelial staining or safety parameters. Conclusions: Topical application of PRO-176 is as safe and effective as the controls. Both groups were clinically similar in terms of efficacy and safety. The results support the hypothesis that ophthalmic DMPC-based nanoemulsion may improve clinical parameters and symptoms in patients with DED. This trial is registered with NCT04111965.

Systematic Review of the Clinical and Experimental Research Assessing the Effects of Craniosynostosis on the Brain.

Although neurocognitive impairment has been considered as the main argument for the surgical treatment of craniosynostosis (CS), recent studies reported subtle deficits in neurological function even in operated patients. However, the cause of these deficits remains poorly understood. This systematic review sought to examine the impact of CS on the brain microstructure, mainly on functional connectivity, and comprehensively summarize the clinical and experimental research available on this topic. A systematic review was performed considering the publications of the last 20 years in PubMed and Web of Science, including relevant human and animal studies of the types of brain-microstructure disturbances in CS. Among the 560 papers identified, 11 were selected for analysis. Seven of those were conducted in humans and 4 in animal models. Resting-state functional magnetic resonance imaging, task-based magnetic resonance imaging, and diffusion tensor imaging were the main instruments used to investigate brain connectivity in humans. The main findings were increased connectivity of the posterior segment of cingulum gyri, reduced interconnectivity of the frontal lobes, and reduced diffusivity on diffusion tensor imaging, which were associated with hyperactivity behaviors and poorer performance on neurocognitive tests. Conversely, despite the lack of evidence of brain dysfunction in animal studies, they reported a tendency toward the development of hyperactive behaviors and impairment of neurocognitive function. Skull restriction caused by CS apparently chronically increases the intracranial pressure and produces white matter injuries. The current evidence supports the contention that an early surgical approach could minimize brain-connectivity impairment in this context.

Evaluation of the Rheological Properties, Preclinical Safety, and Clinical Effectiveness of a New Dispersive Ophthalmic Viscoelastic Device for Cataract Surgery.

Purpose: To evaluate the rheological properties of the ophthalmic viscoelastic device (OVD) PRO-149, its preclinical safety, and its effectiveness when used during cataract surgery in patients with age-related cataract. Material and Methods: Control (HEC) and test (PRO-149) OVDs were compared through rheological measures, by two preclinical safety studies in rabbits, and under normal-use conditions during cataract removal and lens implantation in a parallel randomized clinical trial. Results: Rheological properties were determined. Preclinical studies did not find any evidence of safety issues or toxicity. In the clinical trial, 36 subjects were included. After 29 days, there were no statistically significant differences in mean percentage of endothelial cell count change or in the postoperative intraocular pressure between groups. There were no significant differences between OVDs for any safety parameter studied. Finally, PRO-149 showed a statistically significant improvement in surgeon rating for ease of use during extraction (p < 0.05). Conclusion: PRO-149 is a dispersive OVD. The rabbit models did not find evidence of clinical alterations or toxicity. The results of the clinical study support that the two studied OVDs were clinically similar in terms of safety and effectiveness for cataract surgery. Trial Registration: The trial is registered at Clinical Trials.gov at NCT04702802 (21-01-11).

Reexamining Ophthalmic Drugs, Safety and Tolerability in Phase 1 Clinical Trials.

PURPOSE: The purpose of this study was to evaluate the safety and tolerability profile of drugs used for treating common eye disorders when applied to normal healthy volunteers (NHVs) as explored in phase 1 trials. SUBJECTS AND METHODS: A total of 166 NHVs were identified in six phase 1 trials, examined in a retrospective analysis. The primary endpoints were visual comfort (by ocular comfort index, OCI) and safety (laboratory evaluations, vital signs (VS), visual acuity (VA), intraocular pressure (IOP), lissamine green and fluorescein staining, conjunctival hyperemia, chemosis, and adverse events' incidence (AE)). RESULTS: Compared to baseline, 75.9%, 40.4% and 73.7% of NHV (for lubricant, hypotensive and antibiotic treatments, respectively) improved their OCI score by their final visit. Laboratory evaluations and VS were within normal ranges in 88% of NHV. Similar results were found for VA, corneal and conjunctival staining, and chemosis. IOP decreased significantly in the hypotensive agents' group, trace to mild hyperemia was reported in 32.1%, 27.1%, and 6.8%, respectively. Additionally, lubricant and hypotensive investigational drugs (ID) had a lower risk of incidence of AE than approved drugs (OR 0.856, 95% CI [0.365, 1.999] and 0.636, 95% CI [0.096, 4.197], respectively). Meanwhile, on antibiotic drugs, the risk for ID-related AE was higher (OR 1.313, 95% CI [0.309, 5.583]). CONCLUSION: Phase 1 trials are important in order to ensure the safety and tolerability of ophthalmic medications. This study demonstrates that NHVs do not face a significant risk of harm in these studies, since 98% of the reported AE were mild, and all AE were resolved by the end of the study in which they appeared. TRIAL REGISTRATION: This is a retrospective study of six previously conducted clinical trials, registered on clinicaltrials.gov with the following registration IDs: NCT04081610, NCT03524157, NCT03520348, NCT03966365, NCT03965052 and, NCT03519516.

Annotated world checklist of the Trombiculidae and Leeuwenhoekiidae (17582021) (Acari: Trombiculoidea), with notes on nomenclature, taxonomy, and distribution.

The superfamily Trombiculoidea is a large and diverse group of acarines that comprises six families; of these, the families Trombiculidae and Leeuwenhoekiidae are characterized by larvae commonly known as chiggers that are parasites of terrestrial vertebrates, including humans, and some species are of medical importance as vectors of chigger-borne rickettsiosis (scrub typhus), caused by the rickettsia Orientia tsutsugamushi. This paper presents an annotated checklist of 3,013 generally accepted chigger species, together with their distribution by zoogeographic region, and a non-comprehensive list of synonyms. A total of 58 new combinations are proposed by transferring species to different genera, treating some subgenera as genera, or updating current generic names. The checklist updates earlier catalogs of the world chigger fauna, but because the literature on chigger taxonomy is voluminous and scattered, similar, regional monographs were utilized in constructing the classificatory foundation. This list may not contain every species, synonym or taxonomic rearrangement that has been published, but it reflects the most recent arrangement of chigger taxa. Distribution records are primarily drawn from collection sites listed in the original species descriptions, together with subsequently published geographical records.

Survey Outcomes of Lipedema Reduction Surgery in the United States.

BACKGROUND: Lipedema is a loose connective tissue disease affecting the limbs of women, that is difficult to lose by diet, exercise, or bariatric surgery. Publications from Europe demonstrate that lipedema reduction surgery improves quality of life for women with lipedema. There are no comparable studies in the United States (USA). The aim of this study was to collect data from women with lipedema in the USA who have undergone lipedema reduction surgery in the USA to determine if quality of life, pain, and other measures improved after lipedema reduction surgery. METHODS: Subjects were recruited and consented online for a 166-item questionnaire in REDCap. In total, 148 women answered the questionnaire after undergoing lipedema reduction surgery in the USA. Significance set at P < 0.05 was determined by ANOVA, Tukey's multiple comparison test, or paired t-test. RESULTS: Quality of life improved in 84% and pain improved in 86% of patients. Ambulation improved most in lipedema Stage 3 (96%). Weight loss occurred in all stages by 3 months after surgery. Complications included growth of loose connective tissue within and outside treated areas, tissue fibrosis, anemia, blood clots, and lymphedema. CONCLUSIONS: Women with lipedema noticed significant benefits after lipedema reduction surgery in the USA. Prospective studies are needed to assess benefits and complications after lipedema reduction surgery in the USA.

Effect of different doses of phytase and protein content of soybean meal on growth performance, nutrient digestibility, and bone characteristics of broilers.

This study evaluated the effects of high phytase doses and soybean meal (SBM) with different CP content on growth performance, ileal nutrient digestibility, digestible energy, plasmatic myo-inositol, phosphate release in vitro, and bone composition of broiler chickens. One thousand two hundred 1-day-old broilers were distributed in a 2 × 2 completely randomized factorial arrangement, with 2 phytase doses (1,000 and 2,500 phytase units [FYT]/kg of feed) and 2 SBM with different CP concentrations (45 and 47%), totaling 4 treatments with 12 replicates of 25 birds each. The chickens received feed and water ad libitum. Diets were based on corn and SBM, with different inclusions of soybean hull used to dilute the CP content of SBM according to each treatment. The inclusion of 2,500 FYT increased weight gain from 0 to 21 d (P < 0.05), whereas growth performance from 22 to 42 d was not affected, and SBM had no effect on growth performance. At day 21, ileal digestibility of dry matter, ash, and P, and digestible energy were greater in diets with 2,500 FYT/kg (P < 0.05), as well as phosphate in vitro release (P < 0.01) compared to the lower dose. At day 42, diets with SBM 47% CP and 2,500 FYT/kg promoted greater digestibility of dry matter, ash, CP, Ca, P, and digestible energy (P < 0.001), and greater phosphate release (P < 0.05) in comparison to other treatments. myo-inositol level in the plasma at 21 and 42 d was higher with the use of 2,500 FYT compared to 1,000 FYT (P < 0.05). The higher phytase dose increased tibia ash, toe ash, and Seedor Index (P < 0.05) at day 21, and the Ca content in tibia was higher with 2,500 FYT and SBM 47% CP at day 42. In conclusion, higher phytase doses for broilers improve weight gain, myo-inositol provision, and bone mineral composition. Nutrient ileal digestibility can be enhanced by higher phytase doses when in combination with SBM of greater nutritional quality.

Validation and Analysis of the European Quality Questionnaire in Italian Language.

The European Quality Questionnaire (euroQ2) is the culturally-adapted version to the European context of the Family Satisfaction in Intensive Care Unit (FS-ICU) and Quality of Dying and Death (QODD) tools in a single instrument divided into three parts (the last is optional). These tools were created for an adult setting. The aim of this study was the Italian validation and analysis of the euroQ2 tool. The Italian version of euroQ2 questionnaire was administered to the relatives, over 18 years of age, of adult intensive care unit patients, with the Hospital Anxiety and Depression Scale (HADS) and the Impact of Event Scale-Revised (IES-r). For the re-test phase the questionnaire was administered a second time. One hundred questionnaires were filled in. The agreement between test and retest was between 17-19 out of 20 participants with an upward trend in the re-test phase. A measure of coherence and cohesion between the euroQ2 variables was given by Cronbach's alpha: in the first part of the questionnaire alpha was 0.82, in the second part it was 0.89. The linear Pearson's correlation coefficients between all questions showed a weak positive correlation. The results obtained agreed with the original study. This study showed a good stability of the answers, an indication of an unambiguous understanding of the Italian translation.

Wing size and parity as markers of cohort demography for potential Anopheles (Culicidae: Diptera) malaria vectors in the Republic of Korea.

Wing lengths of parous (P) and nulliparous (NP) PCR-identified female Anopheles belenrae, An. kleini, An. pullus, and An. sinensis were determined from weekly trap collections at Camp Humphreys (CH), Ganghwa Island (GH), and Warrior Base (WB), Republic of Korea (ROK) during Jun-Oct, 2009. Wing length was greatest at the beginning and end of the study period. Wing length of NPs tended to be less than that of Ps before the period of maximum greening (Jul-Aug) but greater thereafter. Larger specimens tended to be Ps, and weekly wing length of Ps appeared less variable than NPs, possibly due to selection. A bimodal wing length frequency distribution of An. sinensis suggested two forms comprising small- (≤4.5 mm, SW) and large-winged females (>4.5 mm, LW). LW comprised the majority of peaks in abundance, however %SW, while still a minority, often increased during these times suggesting a density-dependent effect. At WB and GH, a two to three-week periodicity in %SW was obvious for An. sinensis and An. kleini. Analyses of weather station and satellite data showed that smaller-winged An. sinensis were associated with warmer, more humid, and greener times of the year. SW and LW specimens possibly result from agricultural practices that are common across large areas; regular synchronous peaks of SW and LW were observed from different sites. Peaks in SW Ps followed peaks in NPs in a 'ripple effect' one to two weeks apart, suggesting that wing length combined with parity could be used to follow the emergence and survival of mosquito cohorts.

Psychological preparation reduces preoperative anxiety in children. Randomized and double-blind trial / Preparação psicológica reduz ansiedade pré-operatória de crianças. Ensaio randomizado e duplamente encoberto

Abstract Objective: To verify the effect of psychological preparation on the relief of preoperative anxiety in children and to correlate parents' and children's levels of anxiety. Method: After the approval of the institutional Research Ethics Committee and written consent of the children's parents or guardians, 118 children of both genders were prospectively selected, aged between 2 and 8 years, physical condition classification ASA I, who were treated in the pre-anesthetic evaluation ambulatory of the University Hospital and who underwent ambulatory surgeries at the same hospital. Two controlled groups of 59 children were randomized: control group basic preparation and psychological preparation group. On the day of surgery, all selected children were evaluated regarding their level of anxiety using the modified Yale Preoperative Anxiety Scale and their parents were evaluated regarding their level of anxiety through the Visual Analog Scale. The evaluator was blinded to which study group the child and family member belonged to. Results: Nine children and their family members were excluded per group when the results were analyzed. Children from the prepared group showed significant reductions in their level of anxiety in relation to the control group (p = 0.04). There was no correlation between the level of anxiety of children and their parents' levels (p = 0.78). Conclusion: The psychological preparation was effective in reducing the level of anxiety of children. However, there was no relation between the level of anxiety of children and their parents' level.

Resumo: Objetivos: Verificar o efeito da preparação psicológica no alívio da ansiedade pré-operatória de crianças e avaliar se há correlação com a ansiedade dos pais. Método: Após a aprovação do Comitê de Ética e Pesquisa da Faculdade de Medicina e obtenção do consentimento pelos responsáveis dos pacientes, foram selecionadas prospectivamente 118 crianças, de ambos os sexos, entre dois e oito anos, classificação de estado físico ASA I, atendidas no ambulatório de avaliação pré-anestésica do Hospital Universitário e submetidas a cirurgias ambulatoriais. Foram randomizados dois grupos controlados de 59 crianças: grupo de preparação básica e grupo de preparação psicológica. No dia da cirurgia, todas as crianças foram avaliadas em relação ao seu grau de ansiedade através da Escala de Ansiedade Pré-operatória de Yale Modificada e seus pais, avaliados quanto ao seu nível de ansiedade pela Escala Visual Analógica. O avaliador era cego sobre qual grupo do estudo a criança e seu familiar pertenciam. Resultados: Na análise dos resultados, foram excluídas nove crianças e familiares de cada grupo. As crianças do grupo preparado tiveram reduções significativas no grau de ansiedade em relação ao grupo controle, (p = 0,04). Não houve correlação entre os graus de ansiedade das crianças e seus pais (p = 0,78). Conclusão: A preparação psicológica foi eficaz na redução do grau de ansiedade das crianças no momento da cirurgia. Não houve, entretanto, relação entre os graus de ansiedade dos pais e seus filhos.

Evaluation of embryo collection and transfer days on pregnancy rate of Mangalarga Marchador mares during the breeding season / Evaluación de los días de recolección y transferencia de embriones sobre las tasas de preñez en yeguas Mangalarga Marchador durante la estación de monta / Avaliação do dia da colheita e da transferência de embriões equino da raça Mangalarga Marchador durante a estação de monta

Abstract Background: Proper timing for embryo collection and transfer in horses -which is critical for the success of this biotechnology- is still debated. Additionally, there is little information on this technology under tropical conditions. Objective: To determine the best day for collection and transfer of embryos in Mangalarga Marchador mares under Brazilian northeast's conditions. Methods: Donors (n= 30) and recipients (n= 76) in diestrus phase were selected based on both clinical and gynecology examinations. Estrus was induced on both donor and recipient mares by intramuscular injection of 5 mg Dinoprost, aiming to obtain an ovulation interval of -1 to +3 between recipient and donor. Ovulation was induced with buserelin acetate when the largest follicle reached at least 35 mm in diameter. At this time, mares were subjected to artificial insemination at 48-hour intervals until ovulation. The embryos were collected on days 7, 8, and 9 after ovulation. Results: The embryo collection on day 8 was more efficient (p<0.05) than on day 7, but it was not more effective (p>0.05) than day 9, which presented the same efficiency (p>0.05) as day 7. From a total of 76 embryos transferred to the recipients, that were between days 4 and 9 after ovulation, there was no influence (p>0.05) of the day of transfer on pregnancy rate. Conclusions: The embryo collection must be performed on day 8 after ovulation, and transfer can be performed on any day of that interval (4-9) without affecting the pregnancy rate.

Resumen Antecedentes: El momento mas apropiado para la recolección y transferencia de embriones en equinos -que es fundamental para el éxito de esta biotecnología- continua siendo sujeto de estudio. Además, es escasa la información sobre esta tecnología en condiciones tropicales. Objetivo: Determinar el momento mas adecuado para la recolecta y transferencia de embriones en yeguas Mangalarga Marchador, en las condiciones del nordeste Brasileño. Métodos: Donadoras (n= 30) y receptoras (n= 76) en la fase de diestro se seleccionaron con base en los exámenes clínicos y ginecológicos. El estro de las yeguas donadoras y receptoras fue inducido con 5 mg de Dinoprost, vía intramuscular, intentando obtener un intervalo de ovulación de -1 a +3 entre la receptora y la donadora. La ovulación fue inducida con acetato de buserelina cuando el folículo mayor alcanzó 35 mm de diámetro. En ese momento, las yeguas fueron sometidas a inseminación artificial en intervalos de 48 horas hasta la ovulación. Los embriones fueron recolectados en los días 7, 8 y 9 después de la ovulación. Resultados: La recolecta de embriones en el día 8 fue más eficiente (p<0,05) que en el día 7, pero no fue más efectivo (p>0,05) que en el día 9, el cuál presentó la misma eficiencia (p>0,05) que en el día 7. De un total de 76 embriones transferidos a las receptoras, que se encontraban entre el día 4 y 9 después de la ovulación, no se registró influencia (p>0,05) del día de la transferencia en la tasa de preñez. Conclusiones: La recolecta embrionaria debe ser realizada el día 8 después de la ovulación, y la transferencia puede ser realizada en cualquier día de este intervalo (4 a 9) sin que se afecte la tasa de preñez.

Resumo Antecedentes: A importância do momentoda colheita e da transferência do embrião equino para o sucesso dessa biotécnica em equino continua sem ser completamente entendida. Adicionalmente, existe pouca informação sobre essa tecnologia em condições tropicais. Objetivo: Determinar o melhor dia para colheita e para transferência de embriões em eguas manga larga marchador nas condições do nordeste brasileiro. Métodos: Doadoras (n = 30) e receptoras (n = 76) na fase de diestro foram selecionadas com base nos exames clínico e ginecológicos. O estro das éguas doadoras e receptoras foi induzido com 5 mg de Dinoprost administrado por via intramuscular, buscando obter um intervalo de ovulação de -1 a +3 entre a receptora e a doadora. A ovulação foi induzida com acetato de buserelina quando o foliculo maior alcançou o tamanho de 35 mm de diâmetro. Nesse momento, as éguas foram submetidas a inseminação artificial em intervalos de 48 horas até a ovulação. Os embriões foram colhidos nos dias 7, 8 e 9 depois da ovulação. Resultados: A colheita de embriões no dia 8 foi mais eficiente (p<0,05) do que no dia 7, porem não foi mais efetivo (p>0,05) do que o dia 9, o qual apresentou a mesma eficiência (p>0,05) que o dia 7. De um total de 76 embriões transferidos para as receptoras que se encontravam entre os dias 4 e 9 depois da ovulação, não se registrou influência (p>0,05) do dia da transferência sobre a taxa de prenhez. Conclusões: A colheita embrionária deve ser realizada no dia 8 depois da ovulação, e a transferência pode ser realizada em qualquer dia desse intervalo (4-9) sem que a taxa de prenhez seja afetada.

The microRNA-29a Modulates Serotonin 5-HT7 Receptor Expression and Its Effects on Hippocampal Neuronal Morphology.

miRNAs are master regulators of gene expression in diverse biological processes, including the modulation of neuronal cytoarchitecture. The identification of their physiological target genes remains one of the outstanding challenges. Recently, it has been demonstrated that the activation of serotonin receptor 7 (5-HT7R) plays a key role in regulating the neuronal structure, synaptogenesis, and synaptic plasticity during embryonic and early postnatal development of the central nervous system (CNS). In order to identify putative miRNAs targeting the 3'UTR of 5-HT7R mouse transcript, we used a computational prediction tool and detected the miR-29 family members as the only candidates. Thus, since miR-29a is more expressed than other members in the brain, we investigated its possible involvement in the regulation of neuronal morphology mediated by 5-HT7R. By luciferase assay, we show that miR-29a can act as a post-transcriptional regulator of 5-HT7R mRNA. Indeed, it downregulates 5-HT7R gene expression in cultured hippocampal neurons, while the expression of other serotonin receptors is not affected. From a functional point of view, miR-29a overexpression in hippocampal primary cultures impairs the 5HT7R-dependent neurite elongation and remodeling through the inhibition of the ERK intracellular signaling pathway. In vivo, the upregulation of miR-29a in the developing hippocampus parallels with the downregulation of 5-HT7R expression, supporting the hypothesis that this miRNA is a physiological modulator of 5-HT7R expression in the CNS.

Psychological preparation reduces preoperative anxiety in children. Randomized and double-blind trial.

OBJECTIVE: To verify the effect of psychological preparation on the relief of preoperative anxiety in children and to correlate parents' and children's levels of anxiety. METHOD: After the approval of the institutional Research Ethics Committee and written consent of the children's parents or guardians, 118 children of both genders were prospectively selected, aged between 2 and 8 years, physical condition classification ASA I, who were treated in the pre-anesthetic evaluation ambulatory of the University Hospital and who underwent ambulatory surgeries at the same hospital. Two controlled groups of 59 children were randomized: control group basic preparation and psychological preparation group. On the day of surgery, all selected children were evaluated regarding their level of anxiety using the modified Yale Preoperative Anxiety Scale and their parents were evaluated regarding their level of anxiety through the Visual Analog Scale. The evaluator was blinded to which study group the child and family member belonged to. RESULTS: Nine children and their family members were excluded per group when the results were analyzed. Children from the prepared group showed significant reductions in their level of anxiety in relation to the control group (p=0.04). There was no correlation between the level of anxiety of children and their parents' levels (p=0.78). CONCLUSION: The psychological preparation was effective in reducing the level of anxiety of children. However, there was no relation between the level of anxiety of children and their parents' level.

New records and updated checklist of mosquitoes (Diptera: Culicidae) from Lao People's Democratic Republic, with special emphasis on adult and larval surveillance in Khammuane Province.

A list of mosquitoes from the Nakai Nam Theun National Protected Area along the Nam Theun, Nam Mon, Nam Noy, and Nam On rivers, Nakai District, Khammuane Province, Lao People's Democratic Republic (Lao PDR) is presented. Fifty-four mosquito taxa were identified, including 15 new records in the Lao PDR. A fragment of the mtDNA cytochrome c oxidase subunit I (COI) gene, barcode region, was generated for 34 specimens, and together with four specimens already published, it represented 23 species in eight genera. In addition, an updated checklist of 170 mosquito taxa from Lao PDR is provided based on field collections from Khammuane Province, the literature, and specimens deposited in the Smithsonian Institution, National Museum of Natural History (SI-NMNH), Washington, DC, U.S.A. This paper provides additional information about the biodiversity of mosquito fauna in Lao PDR.

Mosquitoes (Diptera: Culicidae) of Singapore: Updated Checklist and New Records.

Prior to 1965, Singapore was part of the Malaya (now Malaysia) and was usually not mentioned when mosquito records were reported for Malaya. Consequently, many species that occurred in Singapore were not listed in the world mosquito catalog, and the available checklist for Singapore since 1986 is incomplete, with some imprecise species information. In updating this checklist, we examined and verified mosquito specimens collected from Singapore in various depositories, including a thorough review of past taxonomic literature. Here, we report a checklist of 182 mosquito species, 33 new distribution records, and a consolidated status list of vectors for Singapore. As Singapore is a travel hub and hosts one of the busiest container ports in the world, there is a risk of introducing mosquito species and their associated pathogens of human disease to the country. Hence, the distribution records are important to increase our knowledge on mosquito ecology as well as to understand the risk of newly introduced vectors and their associated pathogens.

First Record of Aedes (Stegomyia) malayensis Colless (Diptera: Culicidae) in the Lao People's Democratic Republic, Based on Morphological Diagnosis and Molecular Analysis.

This is the first confirmed record of Aedes (Stegomyia) malayensis Colless from the Lao People's Democratic Republic. Its larvae were collected from rock pools and rock holes along the Nam Noy River in the Nakai Nam Theun National Protected Area, Khammuane Province. Larvae were reared in the laboratory and emerged adults were identified based on morphological characters and mitochondrial DNA analysis, using data from the mitochondrial cytochrome c oxidase subunit I. Detailed photographs of the morphological diagnostic characters and information on the bionomics of Ae. malayensis are included.

Seasonal dynamics of Anopheles species at three locations in the Republic of Korea.

Weekly changes in adult Anopheles species were monitored at Camp Humphreys (CH), Ganghwa Island (GH), and Warrior Base (WB), from May-October, 2009-2010 to explore the relationship between Plasmodium vivax development and vector dynamics in the Republic of Korea (ROK). Adult females were trapped and dissected to determine parity for estimating longevity, mortality, and birthrate. A degree-day (DD) method was used to estimate the extrinsic incubation period (EIP) of P. vivax and duration of the gonotrophic cycle and other life stages. Anopheles sinensis was the predominant species, with satellite data showing peak abundance occurring after the period of maximum greenness. Abundance peaks were location dependent, comprised nulliparous and parous females, and timing could not be fully explained by DD estimation. Parity showed synchronicity between locations and years and was highest for September and lowest during maximum greenness. Mosquito longevity was predicted to exceed the EIP (when malaria transmission is possible) during weeks 29, 31, 34, and near the end of the season. Area-wide changes in parity suggest a common cause; information on local larval habitat and agricultural practices may explain location-specific effects. DD estimates of EIP and parity could be used to predict when conditions are suitable for P. vivax transmission.

Serum levels of RANKL and OPG, and the RANKL/OPG ratio in bisphosphonate-related osteonecrosis of the jaw: Are they useful biomarkers for the advanced stages of osteonecrosis?

BACKGROUND: We determined whether serum levels of Receptor Activator for Nuclear Factor κ B Ligand (RANKL), Osteoprotegerin (OPG), and the RANKL/OPG ratio could be useful biomarkers for the severity of oral lesions in bisphosphonate-related osteonecrosis of the jaw (BRONJ). MATERIAL AND METHODS: A case-control study in which Group 1 consisted of 41 patients with BRONJ due to intravenous bisphosphonates, and Group 2 consisted of 44 healthy control cases. The plasma levels of RANKL and OPG were analyzed by an ELISA assay. The OPG/RANKL ratio was also calculated. We determined if the mean serum values differed among the different stages of BRONJ. RESULTS: Serum levels of RANKL were lower in Group 1 than in Group 2 (p =0.01), and serum levels of OPG were higher in patients with BRONJ than in the controls (p =0.006). The ratio of RANKL/OPG was greater in the controls than in Group 1 (p >0.01). There were no significant differences in the serum levels of RANKL and OPG among the different stages of osteonecrosis (p >0.05). CONCLUSIONS: Serum levels of RANKL and OPG, and the RANKL/OPG ratio were not valuable biomarkers for determining the severity of oral lesions in patients with BRONJ.

Exposed necrotic bone in 183 patients with bisphosphonate-related osteonecrosis of the jaw: Associated clinical characteristics.

BACKGROUND: The main objective of our study was to identify oral symptoms and signs most likely to be associated with the exposure of necrotic bone in bisphosphonate-related osteonecrosis of the jaw (BRONJ). MATERIAL AND METHODS: The study group consisted of 183 patients with BRONJ. We recorded data on the underlying disease, bisphosphonate used, location of osteonecrosis, symptoms, pain, fistula development, suppuration, infection, exposed necrotic bone, and BRONJ stage. RESULTS: The mean age of the patients was 68.22 ± 12.19 years. The sample included 118 (64.5%) women. Breast cancer and multiple myeloma were the most common underlying diseases, and 50 patients received oral bisphosphonates for osteoporosis. Dental extractions (69.4%) and mandibular location (74.3%) predominated. The only two variables influencing the possibility of necrotic bone exposure were intravenous bisphosphonate administration and the presence of an intraoral fistula (p < 0.05). CONCLUSIONS: Intravenous bisphosphonate use and intraoral fistula presence were associated with a major predisposition to bone exposure in patients with BRONJ.