Association of haemoglobin levels in the first trimester and at 26-30 weeks with fetal and neonatal outcomes: a secondary analysis of the Global Network for Women's and Children's Health's ASPIRIN Trial.

OBJECTIVE: Limited data are available from low- and middle-income countries (LMICs) on the relationship of haemoglobin levels to adverse outcomes at different times during pregnancy. We evaluated the association of haemoglobin levels in nulliparous women at two times in pregnancy with pregnancy outcomes. DESIGN: ASPIRIN Trial data were used to study the association between haemoglobin levels measured at 6+0 -13+6  weeks and 26+0 -30+0  weeks of gestation with fetal and neonatal outcomes. SETTING: Obstetric care facilities in Pakistan, India, Kenya, Zambia, The Democratic Republic of the Congo and Guatemala. POPULATION: A total of 11 976 pregnant women. METHODS: Generalised linear models were used to obtain adjusted relative risks and 95% CI for adverse outcomes. MAIN OUTCOME MEASURES: Preterm birth, stillbirth, neonatal death, small for gestational age (SGA) and birthweight <2500 g. RESULTS: The mean haemoglobin levels at 6+0 -13+6  weeks and at 26-30 weeks of gestation were 116 g/l (SD 17) and 107 g/l (SD 15), respectively. In general, pregnancy outcomes were better with increasing haemoglobin. At 6+0 -13+6  weeks of gestation, stillbirth, SGA and birthweight <2500 g, were significantly associated with haemoglobin of 70-89 g/l compared with haemoglobin of 110-129 g/l The relationships of adverse pregnancy outcomes with various haemoglobin levels were more marked at 26-30 weeks of gestation. CONCLUSIONS: Both lower and some higher haemoglobin concentrations are associated with adverse fetal and neonatal outcomes at 6+0 -13+6  weeks and at 26-30 weeks of gestation, although the relationship with low haemoglobin levels appears more consistent and generally stronger. TWEETABLE ABSTRACT: Both lower and some higher haemoglobin concentrations were associated with adverse fetal and neonatal outcomes at 6-13 weeks and 26-30 weeks of gestation.

Cost estimation alongside a multi-regional, multi-country randomized trial of antenatal ultrasound in five low-and-middle-income countries.

BACKGROUND: Improving maternal health has been a primary goal of international health agencies for many years, with the aim of reducing maternal and child deaths and improving access to antenatal care (ANC) services, particularly in low-and-middle-income countries (LMICs). Health interventions with these aims have received more attention from a clinical effectiveness perspective than for cost impact and economic efficiency. METHODS: We collected data on resource use and costs as part of a large, multi-country study assessing the use of routine antenatal screening ultrasound (US) with the aim of considering the implications for economic efficiency. We assessed typical antenatal outpatient and hospital-based (facility) care for pregnant women, in general, with selective complication-related data collection in women participating in a large maternal health registry and clinical trial in five LMICs. We estimated average costs from a facility/health system perspective for outpatient and inpatient services. We converted all country-level currency cost estimates to 2015 United States dollars (USD). We compared average costs across countries for ANC visits, deliveries, higher-risk pregnancies, and complications, and conducted sensitivity analyses. RESULTS: Our study included sites in five countries representing different regions. Overall, the relative cost of individual ANC and delivery-related healthcare use was consistent among countries, generally corresponding to country-specific income levels. ANC outpatient visit cost estimates per patient among countries ranged from 15 to 30 USD, based on average counts for visits with and without US. Estimates for antenatal screening US visits were more costly than non-US visits. Costs associated with higher-risk pregnancies were influenced by rates of hospital delivery by cesarean section (mean per person delivery cost estimate range: 25-65 USD). CONCLUSIONS: Despite substantial differences among countries in infrastructures and health system capacity, there were similarities in resource allocation, delivery location, and country-level challenges. Overall, there was no clear suggestion that adding antenatal screening US would result in either major cost savings or major cost increases. However, antenatal screening US would have higher training and maintenance costs. Given the lack of clinical effectiveness evidence and greater resource constraints of LMICs, it is unlikely that introducing antenatal screening US would be economically efficient in these settings--on the demand side (i.e., patients) or supply side (i.e., healthcare providers). TRIAL REGISTRATION: Trial number: NCT01990625 (First posted: November 21, 2013 on https://clinicaltrials.gov ).

Vistusertib (dual m-TORC1/2 inhibitor) in combination with paclitaxel in patients with high-grade serous ovarian and squamous non-small-cell lung cancer.

Background: We have previously shown that raised p-S6K levels correlate with resistance to chemotherapy in ovarian cancer. We hypothesised that inhibiting p-S6K signalling with the dual m-TORC1/2 inhibitor in patients receiving weekly paclitaxel could improve outcomes in such patients. Patients and methods: In dose escalation, weekly paclitaxel (80 mg/m2) was given 6/7 weeks in combination with two intermittent schedules of vistusertib (dosing starting on the day of paclitaxel): schedule A, vistusertib dosed bd for 3 consecutive days per week (3/7 days) and schedule B, vistusertib dosed bd for 2 consecutive days per week (2/7 days). After establishing a recommended phase II dose (RP2D), expansion cohorts in high-grade serous ovarian cancer (HGSOC) and squamous non-small-cell lung cancer (sqNSCLC) were explored in 25 and 40 patients, respectively. Results: The dose-escalation arms comprised 22 patients with advanced solid tumours. The dose-limiting toxicities were fatigue and mucositis in schedule A and rash in schedule B. On the basis of toxicity and pharmacokinetic (PK) and pharmacodynamic (PD) evaluations, the RP2D was established as 80 mg/m2 paclitaxel with 50 mg vistusertib bd 3/7 days for 6/7 weeks. In the HGSOC expansion, RECIST and GCIG CA125 response rates were 13/25 (52%) and 16/25 (64%), respectively, with median progression-free survival (mPFS) of 5.8 months (95% CI: 3.28-18.54). The RP2D was not well tolerated in the SqNSCLC expansion, but toxicities were manageable after the daily vistusertib dose was reduced to 25 mg bd for the following 23 patients. The RECIST response rate in this group was 8/23 (35%), and the mPFS was 5.8 months (95% CI: 2.76-21.25). Discussion: In this phase I trial, we report a highly active and well-tolerated combination of vistusertib, administered as an intermittent schedule with weekly paclitaxel, in patients with HGSOC and SqNSCLC. Clinical trial registration: ClinicialTrials.gov identifier: CNCT02193633.

A prospective cause of death classification system for maternal deaths in low and middle-income countries: results from the Global Network Maternal Newborn Health Registry.

OBJECTIVE: To describe the causes of maternal death in a population-based cohort in six low- and middle-income countries using a standardised, hierarchical, algorithmic cause of death (COD) methodology. DESIGN: A population-based, prospective observational study. SETTING: Seven sites in six low- to middle-income countries including the Democratic Republic of the Congo (DRC), Guatemala, India (two sites), Kenya, Pakistan and Zambia. POPULATION: All deaths among pregnant women resident in the study sites from 2014 to December 2016. METHODS: For women who died, we used a standardised questionnaire to collect clinical data regarding maternal conditions present during pregnancy and delivery. These data were analysed using a computer-based algorithm to assign cause of maternal death based on the International Classification of Disease-Maternal Mortality system (trauma, termination of pregnancy-related, eclampsia, haemorrhage, pregnancy-related infection and medical conditions). We also compared the COD results to healthcare-provider-assigned maternal COD. MAIN OUTCOME MEASURES: Assigned causes of maternal mortality. RESULTS: Among 158 205 women, there were 221 maternal deaths. The most common algorithm-assigned maternal COD were obstetric haemorrhage (38.6%), pregnancy-related infection (26.4%) and pre-eclampsia/eclampsia (18.2%). Agreement between algorithm-assigned COD and COD assigned by healthcare providers ranged from 75% for haemorrhage to 25% for medical causes coincident to pregnancy. CONCLUSIONS: The major maternal COD in the Global Network sites were haemorrhage, pregnancy-related infection and pre-eclampsia/eclampsia. This system could allow public health programmes in low- and middle-income countries to generate transparent and comparable data for maternal COD across time or regions. TWEETABLE ABSTRACT: An algorithmic system for determining maternal cause of death in low-resource settings is described.

Global Network for Women's and Children's Health Research: probable causes of stillbirth in low- and middle-income countries using a prospectively defined classification system.

OBJECTIVE: We sought to classify causes of stillbirth for six low-middle-income countries using a prospectively defined algorithm. DESIGN: Prospective, observational study. SETTING: Communities in India, Pakistan, Guatemala, Democratic Republic of Congo, Zambia and Kenya. POPULATION: Pregnant women residing in defined study regions. METHODS: Basic data regarding conditions present during pregnancy and delivery were collected. Using these data, a computer-based hierarchal algorithm assigned cause of stillbirth. Causes included birth trauma, congenital anomaly, infection, asphyxia, and preterm birth, based on existing cause of death classifications and included contributing maternal conditions. MAIN OUTCOME MEASURES: Primary cause of stillbirth. RESULTS: Of 109 911 women who were enrolled and delivered (99% of those screened in pregnancy), 2847 had a stillbirth (a rate of 27.2 per 1000 births). Asphyxia was the cause of 46.6% of the stillbirths, followed by infection (20.8%), congenital anomalies (8.4%) and prematurity (6.6%). Among those caused by asphyxia, 38% had prolonged or obstructed labour, 19% antepartum haemorrhage and 18% pre-eclampsia/eclampsia. About two-thirds (67.4%) of the stillbirths did not have signs of maceration. CONCLUSIONS: Our algorithm determined cause of stillbirth from basic data obtained from lay-health providers. The major cause of stillbirth was fetal asphyxia associated with prolonged or obstructed labour, pre-eclampsia and antepartum haemorrhage. In the African sites, infection also was an important contributor to stillbirth. Using this algorithm, we documented cause of stillbirth and its trends to inform public health programs, using consistency, transparency, and comparability across time or regions with minimal burden on the healthcare system. TWEETABLE ABSTRACT: Major causes of stillbirth are asphyxia, pre-eclampsia and haemorrhage. Infections are important in Africa.

Routine antenatal ultrasound in low- and middle-income countries: first look - a cluster randomised trial.

OBJECTIVE: Ultrasound is widely regarded as an important adjunct to antenatal care (ANC) to guide practice and reduce perinatal mortality. We assessed the impact of ANC ultrasound use at health centres in resource-limited countries. DESIGN: Cluster randomised trial. SETTING: Clusters within five countries (Democratic Republic of Congo, Guatemala, Kenya, Pakistan, and Zambia) METHODS: Clusters were randomised to standard ANC or standard care plus two ultrasounds and referral for complications. The study trained providers in intervention clusters to perform basic obstetric ultrasounds. MAIN OUTCOME MEASURES: The primary outcome was a composite of maternal mortality, maternal near-miss mortality, stillbirth, and neonatal mortality. RESULTS: During the 24-month trial, 28 intervention and 28 control clusters had 24 263 and 23 160 births, respectively; 78% in the intervention clusters received at least one study ultrasound; 60% received two. The prevalence of conditions noted including twins, placenta previa, and abnormal lie was within expected ranges. 9% were referred for an ultrasound-diagnosed condition, and 71% attended the referral. The ANC (RR 1.0 95% CI 1.00, 1.01) and hospital delivery rates for complicated pregnancies (RR 1.03 95% CI 0.89, 1.20) did not differ between intervention and control clusters nor did the composite outcome (RR 1.09 95% CI 0.97, 1.23) or its individual components. CONCLUSIONS: Despite availability of ultrasound at ANC in the intervention clusters, neither ANC nor hospital delivery for complicated pregnancies increased. The composite outcome and the individual components were not reduced. TWEETABLE ABSTRACT: Antenatal care ultrasound did not improve a composite outcome that included maternal, fetal, and neonatal mortality.

The Role of Polycystic Kidney Disease-Like Homologs in Planarian Nervous System Regeneration and Function.

Planarians are an excellent model for investigating molecular mechanisms necessary for regenerating a functional nervous system. Numerous studies have led to the generation of extensive genomic resources, especially whole-animal single-cell RNA-seq resources. These have facilitated in silico predictions of neuronal subtypes, many of which have been anatomically mapped by in situ hybridization. However, our knowledge of the function of dozens of neuronal subtypes remains poorly understood. Previous investigations identified that polycystic kidney disease (pkd)-like genes in planarians are strongly expressed in sensory neurons and have roles in mechanosensation. Here, we examine the expression and function of all the pkd genes found in the Schmidtea mediterranea genome and map their expression in the asexual and hermaphroditic strains. Using custom behavioral assays, we test the function of pkd genes in response to mechanical stimulation and in food detection. Our work provides insight into the physiological function of sensory neuron populations and protocols for creating inexpensive automated setups for acquiring and analyzing mechanosensory stimulation in planarians.

Birth attendants as perinatal verbal autopsy respondents in low- and middle-income countries: a viable alternative?

OBJECTIVE: To assess the feasibility of using birth attendants instead of bereaved mothers as perinatal verbal autopsy respondents. METHODS: Verbal autopsy interviews for early neonatal deaths and stillbirths were conducted separately among mothers (reference standard) and birth attendants in 38 communities in four developing countries. Concordance between maternal and attendant responses was calculated for all questions, for categories of questions and for individual questions. The sensitivity and specificity of individual questions with the birth attendant as respondent were assessed. FINDINGS: For early neonatal deaths, concordance across all questions was 94%. Concordance was at least 95% for more than half the questions on maternal medical history, birth attendance and neonate characteristics. Concordance on any given question was never less than 80%. Sensitivity and specificity varied across individual questions, more than 80% of which had a sensitivity of at least 80% and a specificity of at least 90%. For stillbirths, concordance across all questions was 93%. Concordance was 95% or greater more than half the time for questions on birth attendance, site of delivery and stillborn characteristics. Sensitivity and specificity varied across individual questions. Over 60% of the questions had a sensitivity of at least 80% and over 80% of them had a specificity of at least 90%. Overall, the causes of death established through verbal autopsy were similar, regardless of respondent. CONCLUSION: Birth attendants can substitute for bereaved mothers as verbal autopsy respondents. The questions in existing harmonized verbal autopsy questionnaires need further refinement, as their sensitivity and specificity differ widely.

An alternative strategy for perinatal verbal autopsy coding: single versus multiple coders.

OBJECTIVE: To determine the comparability between cause of death (COD) by a single physician coder and a two-physician panel, using verbal autopsy. METHODS: The study was conducted between May 2007 and June 2008. Within a week of a perinatal death in 38 rural remote communities in Guatemala, the Democratic Republic of Congo, Zambia and Pakistan, VA questionnaires were completed. Two independent physicians, unaware of the others decisions, assigned an underlying COD, in accordance with the causes listed in the chapter headings of the International classification diseases and related health problems, 10th revision (ICD-10). Cohen's kappa statistic was used to assess level of agreement between physician coders. RESULTS: There were 9461 births during the study period; 252 deaths met study enrolment criteria and underwent verbal autopsy. Physicians assigned the same COD for 75% of stillbirths (SB) (K = 0.69; 95% confidence interval: 0.61-0.78) and 82% early neonatal deaths (END) (K = 0.75; 95% confidence interval: 0.65-0.84). The patterns and proportion of SBs and ENDs determined by the physician coders were very similar compared to causes individually assigned by each physician. Similarly, rank order of the top five causes of SB and END was identical for each physician. CONCLUSION: This study raises important questions about the utility of a system of multiple coders that is currently widely accepted and speculates that a single physician coder may be an effective and economical alternative to VA programmes that use traditional two-physician panels to assign COD.

Long-term semi-continuous production of carbohydrate-enriched microalgae biomass cultivated in low-loaded domestic wastewater.

The production of carbohydrate-enriched biomass from waste streams as a sustainable biofuel precursor is a noteworthy endeavor. This study investigates the long-term microalgae cultivated under low domestic wastewater loads and different hydraulic retention times (HRT) in a semi-continuous photobioreactor. The influence of operational conditions, the microalgae interaction with carbon, nutrients availability, and microbial population in terms of carbohydrate content were elucidated. The results revealed that the operation at similar low nutrients and carbon loads maintained at three different hydraulic retention times (HRT) of 10, 8, and 6 days caused different patterns in nutrients uptake and biomass composition. Particularly, the carbohydrate accumulation was greatly influenced by the unbalance in the N:P ratios than complete depletion of the nutrients. Hence, during the period operated at HRT of 10 d, high nutrients removal efficiencies were observed while gradually increasing carbohydrate content up to 57% in dry cell weight (DCW). Afterward, the decrease to 8 and 6 d of HRT showed lower nutrient consumption with depleted alkalinity, reaching an appreciably high carbohydrate accumulation of up to 46%, and 56%, respectively. The biomass concentration decreased in the order of HRT of 10, 8, and 6 days. This study demonstrated that microalgae adapted to low carbon and nutrient loads could still accumulate high carbohydrate at shorter HRT using domestic wastewater as substrate.

Coronary heart disease risk assessment in HIV-infected patients: a comparison of Framingham, PROCAM and SCORE risk assessment functions.

OBJECTIVES: The aim of this was to compare the performance of the Framingham, Systematic Coronary Risk Evaluation (SCORE) and Prospective Cardiovascular Munster (PROCAM) scoring systems in the risk assessment of HIV-infected patients with no overt vascular disease. METHODS: A cross-sectional study of 220 HIV-infected patients was conducted at the outpatient clinic of a referral and training centre in infectious and parasitic diseases in Belo Horizonte, Brazil. The Framingham, SCORE and PROCAM equations were calculated. Patients were classified as having low, moderate or high risk, which according to the Framingham and PROCAM equations corresponded to < 10%, 10-20% and > 20% respectively, and according to SCORE corresponded to < 3%, 3-4% and > or = 5% respectively. Cohen's kappa coefficient was used to assess agreement between the methods. RESULTS: Of a total of 220 HIV-infected patients, 56 were antiretroviral (ARV)-naïve while 164 had already been treated with ARV. The prevalence of patients with a high 10-year cardiovascular risk was 3.7%, 2.5% and 1.9% according to the Framingham, PROCAM and SCORE equations respectively. The degree of agreement was moderate between the Framingham and PROCAM risk estimates (kappa = 0.433; p < 0.001), poor-to-fair between the Framingham and SCORE estimates (kappa = 0.220; p < 0.001) and moderate between the PROCAM and SCORE systems (kappa = 0.478; p < 0.001). CONCLUSIONS: There are differences in risk assessment and in the identification of high risk individuals between the three risk functions under evaluation and only a prospective study will be capable of assessing which offers the best current sensitivity, specificity and predictive values for the population under investigation.

When reporting Nocardia spp is not enough. Brain abscess caused by Nocardia farcinica.

Abscesses caused by the genus Nocardia spp are relatively rare, accounting for approximately 2 % of all brain abscesses, but with a significantly higher mortality. Special stains of brain abscess material from a 60-year-old man showed Gram-positive branching bacilli and the presence of long, acid-fast branching filamentous bacilli suggesting Nocardia infection. Presented here is a case of multidisciplinary management of a patient who developed cerebral abscesses by Nocardia farcinica, confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), that was susceptible to trimethoprim/sulfamethoxazole, linezolid, imipenem and not susceptible to minocycline. This case highlights the importance of performing subtyping and antimicrobial testing in order to improve clinical and treatment outcomes due to patterns of antibiotics resistance among Nocardia species.

Using verbal autopsy to ascertain perinatal cause of death: are trained non-physicians adequate?

OBJECTIVES: To develop a standardized verbal autopsy (VA) training program and evaluate whether its implementation resulted in comparable knowledge required to classify perinatal cause of death (COD) by physicians and non-physicians. METHODS: Training materials, case studies, and written and mock scenarios for this VA program were developed using conventional VA and ICD-10 guidelines. This program was used to instruct physicians and non-physicians in VA methodology using a train-the-trainer model. Written tests of cognitive and applied knowledge required to classify perinatal COD were administered before and after training to evaluate the effect of the VA training program. RESULTS: Fifty-three physicians and non-physicians (nurse-midwives/nurses and Community Health Workers [CHW]) from Pakistan, Zambia, the Democratic Republic of Congo, and Guatemala were trained. Cognitive and applied knowledge mean scores among all trainees improved significantly (12.8 and 28.8% respectively, P < 0.001). Cognitive and applied knowledge post-training test scores of nurse-midwives/nurses were comparable to those of physicians. CHW (high-school graduates with 15 months or less formal health/nursing training) had the largest improvements in post-training applied knowledge with scores comparable to those of physicians and nurse-midwives/nurses. However, CHW cognitive knowledge post-training scores were significantly lower than those of physicians and nurses. CONCLUSIONS: With appropriate training in VA, cognitive and applied knowledge required to determine perinatal COD is similar for physicians and nurses-midwives/nurses. This suggests that midwives and nurses may play a useful role in determining COD at the community level, which may be a practical way to improve the accuracy of COD data in rural, remote, geographic areas.

A GABAergic Maf-expressing interneuron subset regulates the speed of locomotion in Drosophila.

Interneurons (INs) coordinate motoneuron activity to generate appropriate patterns of muscle contractions, providing animals with the ability to adjust their body posture and to move over a range of speeds. In Drosophila larvae several IN subtypes have been morphologically described and their function well documented. However, the general lack of molecular characterization of those INs prevents the identification of evolutionary counterparts in other animals, limiting our understanding of the principles underlying neuronal circuit organization and function. Here we characterize a restricted subset of neurons in the nerve cord expressing the Maf transcription factor Traffic Jam (TJ). We found that TJ+ neurons are highly diverse and selective activation of these different subtypes disrupts larval body posture and induces specific locomotor behaviors. Finally, we show that a small subset of TJ+ GABAergic INs, singled out by the expression of a unique transcription factors code, controls larval crawling speed.

Persephin, a novel neurotrophic factor related to GDNF and neurturin.

A novel neurotrophic factor named Persephin that is approximately 40% identical to glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) has been identified using degenerate PCR. Persephin, like GDNF and NTN, promotes the survival of ventral midbrain dopaminergic neurons in culture and prevents their degeneration after 6-hydroxydopamine treatment in vivo. Persephin also supports the survival of motor neurons in culture and in vivo after sciatic nerve axotomy and, like GDNF, promotes ureteric bud branching. However, in contrast to GDNF and NTN, persephin does not support any of the peripheral neurons that were examined. Fibroblasts transfected with Ret and one of the coreceptors GFRalpha-1 or GFRalpha-2 do not respond to persephin, suggesting that persephin utilizes additional, or different, receptor components than GDNF and NTN.

[Intermediate-term outcome of glaucoma drainage devices]. / Resultados a medio plazo de los dispositivos de drenaje para glaucoma.

OBJECTIVE: To study the intermediate-term results of glaucoma drainage devices (DDG) with respect to control of intraocular pressure (IOP), control of glaucoma, and maintenance of pre-operative visual acuity. METHODS: This was a retrospective cohort study of 86 eyes in 77 patients in whom a DDG was implanted, using descriptive statistics and survival analysis. RESULTS: Success was achieved in 53 eyes (61.6%), complete (without treatment) in 34 eyes (39.5%) and qualified (needing treatment) in 19 eyes (22.1%). In the 33 eyes where the DDG treatment was unsuccessful, poor IOP control occurred in 13 eyes - (15.1%), and complications occurred in 20 eyes (23.2%) resulting in a severe reduction or loss of visual acuity (plate exposure, suprachoroidal hemorrhage, retinal detachment). IOP control was obtained in 66 eyes (76.7%), 47 of them without treatment (54.6%), although on 13 occasions the overall treatment failed due to complications occurring. Despite IOP control, glaucoma progression occurred in 7 eyes (8.1%). Preoperative vision was maintained in 46 eyes (53.5%), but decreased by 3 or more lines in 20 eyes (46.5%); bullous kerathopathy was the most frequent cause of the worsening. Loss of light perception occurred in 21 eyes (24.4%) and 4 eyes (4.6%) were eviscerated. CONCLUSIONS: DDG are an effective surgical option for control of IOP when conventional surgery has a poor prognosis, but they are associated with an increased risk of serious complications and loss of visual acuity in a significant proportion of cases.

Formulations based on solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for cutaneous use: A review.

Cutaneous use of lipid nanoparticles (solid lipid nanoparticles, SLN and nanostructured lipid carriers, NLC) has been showing promising results. These systems consist of low viscosity aqueous dispersions, being usually employed by means of semi-solid formulations with adequate consistency for skin application. This review addresses the cutaneous use of lipid nanoparticles for therapeutic and cosmetic applications. Initially, general information related to pharmaceutical semi-solid formulations is presented. Afterwards, the effects of SLN and NLC on the skin, and technological aspects related to semi-solid systems based on SLN or NLC are described. Finally, the most relevant studies related to the formulations based on SLN and NLC, for cosmetic and therapeutic applications, are reported. Notwithstanding the cutaneous use of SLN and NLC has been proposed for both local and transdermal delivery, the reported studies show promising results only for local application. In this sense, more research is required to better understanding the interaction mechanisms of lipid nanoparticles with skin lipids. Furthermore, the development of standard methods for skin experiments with nanoparticles is necessary.

Determination of a series of quinolones in pig plasma using solid-phase extraction and liquid chromatography coupled with mass spectrometric detection Application to pharmacokinetic studies.

A simple and sensitive liquid chromatography (LC) method was developed for the simultaneous determination of eight quinolones in pig plasma samples. The following two methods of detection were used: ultraviolet (UV) and mass spectrometry with electrospray ionization (ESI/MS). Sample preparation consisted of solid-phase extraction (SPE) on Strata X cartridges prior to the analysis by LC/UV or LC/ESI/MS. The recovery, linearity, limit of detection (LOD) and limit of quantification (LOQ), precision and accuracy of the method were evaluated using spiked pig plasma samples. The suitability of the method for pharmacokinetic studies was evaluated by determining the concentrations of enrofloxacin (ENR) and ciprofloxacin (CIP) also in pig plasma, after administration of 200mg of enrofloxacin per kilogram of fodder during 5 consecutive days.

Exploiting HPV-Induced Carcinogenesis for a Rational Drug Development in Cervical Cancer.

Cervical carcinomas are almost universally associated with high-risk human papillomavirus (HPV) infections, and are a leading cause of cancer death in women worldwide. Since the late 1990s, when a spate of studies reported the benefit of cisplatin-based chemotherapy, there had been a dearth of clinical trials in cervical cancer (CC). More effective therapies in locally advanced and recurrent or metastatic CC are an urgent clinical need. In the era of molecular oncology one should look beyond conventional chemoradiation and chemotherapy for locally advanced and advanced CC. The fact that the initiating oncogenic insult, infection with a high-risk HPV and viral oncoprotein expression is common to almost all CC offers unique opportunities for disease control. Diverse biologic pathways with an implication in the development and progression of CC are being explored. For the first time, increase in overall survival has recently been obtained for advanced CC patients with a target drug, the antiangiogenic agent bevacizumab, and durable complete responses after HPV-targeted adoptive T cell therapy in metastatic CC patients were achieved. In this review, we will summarize molecular aspects of HPV infection focusing on potential targets to stop the carcinogenic process, present updated drug development data, and discuss challenges and prospects for the future.