A Single Electrochemical Biosensor Designed to Detect Any Virus.

Viruses are the primary cause of many infectious diseases in both humans and animals. Various testing methods require an amplification step of the viral RNA sample before detection, with quantitative reverse transcription polymerase chain reaction (RT-qPCR) being one of the most widely used along with lesser-known methods like Nucleic Acid Sequence-Based Amplification (NASBA). NASBA offers several advantages, such as isothermal amplification and high selectivity for specific sequences, making it an attractive option for low-income facilities. In this research, we employed a single electrochemical biosensor (E-Biosensor) designed for potentially detecting any virus by modifying the NASBA protocol. In this modified protocol, a reverse primer is designed with an additional 22-nucleotide sequence (tag region) at the 5'-end, which is added to the NASBA process. This tag region becomes part of the final amplicon generated by NASBA. It can hybridize with a single specific E-Biosensor probe set, enabling subsequent virus detection. Using this approach, we successfully detected three different viruses with a single E-Biosensor design, demonstrating the platform's potential for virus detection.

Long-term effects of photobiomodulation therapy on blood pressure in obese rats induced by a high-fat diet.

The main cardiovascular disease risk associated with obesity is hypertension. The therapeutic use of photobiomodulation therapy (PBM) is suggested for the treatment of wound healing, osteoarthritis, and arterial diseases. However, few studies have measured how red laser (at 660 nm) acts over hypertension, and any of those studies used experimental obesity model. The aim of the study was an attempt to evaluate the long-term effect of PBM on systolic blood pressure in an animal model of obesity, induced by a high-fat diet (HFD). Our results indicate that PBM carried out 3 days a week was able to prevent the increase in blood pressure (133.75 ± 4.82 mmHg, n = 8) induced by a high-fat diet (150.00 ± 4.57 mmHg, n = 8; p < 0.05), restore nitric oxide levels (control: 31.7 ± 5.5 µM, n = 8; HFD + PBM: 29.9 ± 3.7 µM, n = 8 > HFD: 22.2 ± 2.9 µM, n = 8, p < 0.05), decrease lipoperoxidation (control: 1.65 ± 0.25 nM, n = 8; HFD + PBM: 2.05 ± 0.55 nM, n = 8 < HFD: 3.20 ± 0.47 nM, n = 8; p < 0.05), and improve endothelial function (pD2 control: 7.39 ± 0.08, n = 8 > pD2 HFD + PBM: 7.15 ± 0.07, n = 8 > HFD: 6.94 ± 0.07, n = 8; p < 0.05). Our results indicate that PBM prevents the elevation of blood pressure in an obese animal model by a mechanism that involves improvement of endothelial function through an antioxidant effect.

Effects of 12 Weeks of Daily Melatonin Administration on Inflammatory Markers and Adipose Tissue Mass of Rats under Hypoestrogenism.

Background and Objectives: The hormonal state of hypoestrogenism is associated with the accumulation of white adipose tissue, which can induce an increase in pro-inflammatory markers, leading to progressive health complications. Melatonin can act on adipose tissue mass, promoting its reduction and influencing inflammation, reducing IL-6 and releasing IL-10, pro- and anti-inflammatory markers, respectively. However, the role of melatonin regarding such parameters under the context of hypoestrogenism remains unknown. The aim of this study was to determine the effect of 12 weeks of hypoestrogenism and melatonin on white adipose tissue mass and circulating levels of IL-6, IL-10, TGF-ß-1, and leukotriene C4 (LTC4). Materials and Methods: The animals (Wistar rats with sixteen weeks of age at the beginning of the experiment) under hypoestrogenism were submitted to the surgical technique of bilateral ovariectomy. The animals received melatonin (10 mg·kg-1) or vehicles by orogastric gavage every day for 12 weeks and administration occurred systematically 1 h after the beginning of the dark period. White adipose tissue (perigonadal, peritoneal, and subcutaneous) was collected for mass recording, while blood was collected for the serum determination of IL-6, IL-10, TGF-ß-1, and LTC4. Results: Hypoestrogenism increased the perigonadal and subcutaneous mass and IL-6 levels. Melatonin kept hypoestrogenic animals in physiological conditions similar to the control group and increased thymus tissue mass. Conclusions: Hypoestrogenism appears to have a negative impact on white adipose tissue mass and IL-6 and although melatonin commonly exerts a significant effect in preventing these changes, this study did not have a sufficiently negative impact caused by hypoestrogenism for melatonin to promote certain benefits.

Immunogenicity and Protection by DnaK and SpaA Recombinant Proteins Against Erysipelothrix Rhusiopathiae in a Murine Model.

BACKGROUND/AIMS: Swine erysipelas is a disease caused by Erysipelothrix rhusiopathiae, a Gram-positive bacillus, which has great economic importance because it leads to the loss of the swine herd. To control this disease, animals are immunized with a cellular vaccine of killed or attenuated E. rhusiopathiae, but even with herd vaccination, cases of swine erysipelas outbreaks have been reported in the United States, China and Japan, leading to the search for other antigenic components of the bacteria that may promote greater protection against E. rhusiopathiae. The surface protein SpaA from E. rhusiopathiae has been shown to be a candidate to constitute a subunit vaccine, since it has already been reported to induce a host immune response against the bacterium. DnaK, a hsp70 molecular chaperone, also seems to be a good candidate in the composition of a vaccine, as it has been demonstrated to be an antigenic protein of the bacteria. METHODS: This work evaluated the immunogenicity and protection induced by the E. rhusiopathiaee SpaA and DnaK recombinant proteins in a murine model, by intramuscular administration to mice with two doses of 100 µg at 21-day interval between them. The candidate proteins were tested either separately and together, compared with the commercial vaccine and the non-vaccination condition, and mice were challenged with a virulent strain of E. rhusiopathiae. Serum was collected to assess the produced antibodies and peripheral blood cells, whereas spleen and kidney tissues were assayed for E. rhusiopathiae presence by colony counting. RESULTS: A survival curve of the animals was performed, which confirmed the protection induced by the proteins. IgG antibodies increased in the animal serum inoculated with the proteins when compared to the control, and a significant delay in disease symptoms was observed. CONCLUSION: These results suggest that E. rhusiopathiae DnaK and SpaA are immunogenic in mice and interfere with the disease development.

Hemoperitoneum due to rupture of intra-abdominal varices.

Portal hypertension, responsible for the formation of oesophageal varices, also generates intra-abdominal varicose dilations, especially of the perisplenic and mesenteric veins, which, like the oesophageal veins, are susceptible to rupturing and bleeding, in this case within the peritoneal cavity. However, the spontaneous rupture of these intraperitoneal varices is a rare complication, and poorly described in the literature. We present the case of a 72-year-old woman with CHILD B liver cirrhosis of unknown aetiology with portal hypertension on primary prophylaxis with carvedilol.

Liver abscess due to parvimonas micra.

Liver abscesses are an entity that sets out a diagnostic challenge with a severe clinical course and non-negligible mortality. Their origin is usually bacterial (>80%), parasitic, mixed or, more rarely, fungal. We present the case report of a 45-year-old man, native of Ghana, with no relevant medical-surgical history, was admitted for septic shock with multiple organ dysfuntion syndrome. Complementary imaging tests revealed a liver abscess in segments IV and VII measuring 60x45x54 mm, so antibiotic treatment with piperacillin-tazobactam was started and a pigtail drainage was placed. In blood cultures, the microorganism parvimonas micra (anaerobic gram-positive cocci) was isolated with high degree of sensitivity rates to penicillin, clindamycin and metronidazole. Treatment was de-escalated to clindamycin until completing 4 weeks of intravenous treatment. Control CT showed a decrease in the size of the abscess and pigtail drainage was removed.

Topographic and Morphometric Study of the Foramen Spinosum of the Skull and Its Clinical Correlation.

Background and Objectives: The spinous foramen (FS) of the skull is an opening located in the greater wing of the sphenoid bone at the base of the skull, and it includes the middle meningeal vessels and the meningeal branch of the mandibular trigeminal nerve. The FS is commonly used as an anatomical landmark in neurosurgical procedures and neuroimaging of the middle cranial fossa because of its relationship with other cranial foramina and surrounding vascular and nervous structures. Thus, specific knowledge of its topography and possible anatomical variations is important regarding some surgical interventions and skull imaging. The aim of this study was to provide further details on the morphology of the FS of the skull by evaluating its topographic and morphometric relationships and correlating the findings with clinical practice. Materials and Methods: Thirty dried skulls of human skeletons from body donors from the collection of the Laboratory of Anatomical Microdissection at a medical school were used. The metric dimensions and variations of the FS and its relationship with adjacent bone structures were analyzed with an interface digital microscope. Results: The results showed the bilateral presence of the FS in all skulls; however, differences were observed in the shape, diameter, and topography in relation to the foramen ovale and the spine of the sphenoid. The FS was present in the greater wing of the sphenoid bone; however, in one skull, it was located in the lateral lamina of the pterygoid process. The FS was smaller than the foramen ovale. A round and oval FS shape was the most common (42.1% and 32.8% of the samples, respectively), followed by drop-shaped (12.5%) and irregular-shaped (12.5%) foramina. Conclusions: In conclusion, FS variations among individuals are common and must be considered by surgeons during skull base interventions in order to avoid accidents and postoperative complications.

Apoptosis and Oxidative Stress Triggered by Carbon Black Nanoparticle in the LA-9 Fibroblast.

BACKGROUND/AIMS: A new type of nanoparticle, called NP CB-EDA (Black Carbon modified with ethylenediamine), is commonly used in the oil industry. In the literature, few studies are found in biological models, making NP-EDA potential cytotoxicity in organisms unclear. As its large surface area is capable of interacting with the biological system, that interaction could lead to factors harmful to health. The objective of this study was to investigate the cytotoxic effect of NP CB-EDA on fibroblasts LA-9 at 24 and 48 hours, at different concentrations of the nanoparticle (1, 50, 250, 500 and 1000 µg/ml). METHODS: NP CB-EDA was characterized by TEM microscopy and its effect on cell viability (MTT method), cell morphology (optical microscopy), cell membrane (lactate dehydrogenase release - LDH), oxidative stress pathways (species levels reactive oxygen, ROS and nitrogen, NOS) and apoptosis/necrosis (flow cytometry) were evaluated. RESULTS: The results show that NP CB-EDA at concentrations of 500 and 1000 µg/ml form clusters. The nanoparticle can be absorbed by cells decreasing cell viability. There was damage to the cell membrane of fibroblasts LA 9, an increase in the production of ROS, NOS and pro-inflammatory interleukins TNF-α and IL-6; it was also observed an increase in % of cells in the state of apoptosis in the two periods analyzed, being this response more significant in 24 hours, and concentrations of 250, 500 and 1000 µg/ml presenting higher cytotoxicity. CONCLUSION: The data suggest that NP CB-EDA in fibroblasts LA9 presents cytotoxic potential, which is associated with oxidative stress and apoptosis.

Antitumor Effect of IL-2 and TRAIL Proteins Expressed by Recombinant Salmonella in Murine Bladder Cancer Cells.

BACKGROUND/AIMS: Cancer is the second most deadly disease in the world. The bladder cancer is one of the most aggressive types and shows a continuous increase in the number of cases. The use of bacteria as live vectors to deliver molecules directly to the tumor is a promising tool and has been used as an adjuvant treatment against several types of cancer. The aim of this study was to investigate the antitumor effect of Interleukin 2 (IL-2), TNF-related apoptosis-inducing ligand (TRAIL) and protein MIX against murine bladder cancer cells, lineage MB49. METHODS: The attenuated Salmonella strain SL3261 was transformed by inserting the IL-2 and TRAIL genes. The effects of proteins on cell viability (MTT method), cell morphology (optical microscopy), cell recovery (clonogenic assay), cell membrane (lactate dehydrogenase release - LDH), on oxidative stress pathway (levels of nitric oxide, NO) and apoptosis (flow cytometry and high resolution epifluorescence images) were evaluated at intervals of 24 and 48 hours of action. RESULTS: The results showed that there was a decrease in cell viability via damage to the cell membrane, alteration of cell morphology, non-recovery of cells, increase in the production of NO and incubate for of cells in the state of apoptosis in the two periods analyzed. CONCLUSION: The data presented suggest that IL-2, TRAIL and their MIX proteins in MB49 cells have cytotoxic potential and that this is associated with oxidative stress and apoptosis pathways. These results may contribute to the development of new therapeutic strategies for bladder cancer.

The NEWgeneratorTM non-sewered sanitation system: Long-term field testing at an informal settlement community in eThekwini municipality, South Africa.

Globally, there is a dire need for a new class of advanced non-sewered sanitation systems (NSSS) to provide onsite wastewater treatment that is capable of meeting stringent discharge or reuse criteria. These systems need to be simple to operate and maintain, reliable, and resilient to unreliable electrical service. The NEWgenerator (NG) is a compact, automated, solar-powered wastewater treatment system comprised of three major treatment processes: anaerobic membrane bioreactor (AnMBR), nutrient capture system (NCS) with ion exchange and carbon sorption, and electrochlorination (EC). The NG system operated at an informal settlement community in South Africa over a 534 d period, treating high-strength blackwater (BW) and yellow water (YW) from a public toilet facility. Over three test stages (BW, BW + YW, BW) that included several periods of dormancy, the NG system was able to provide a high level of removal of total suspended solids (97.6 ± 3.1%), chemical oxygen demand (94.5 ± 5.0%), turbidity (96.3 ± 9.7%), color (92.0 ± 10.5%), total nitrogen (82.1 ± 24.0%), total phosphorus (43.0 ± 22.1%), E. coli (7.4 ± 1.5 LRV, not detected in effluent), and helminth ova (not detected in effluent). The treatment levels met most of the ISO 30500 NSSS standard for liquid effluent and local water reuse criteria. A series of maintenance events were successfully conducted onsite over the 534 d field trial: two membrane cleanings, two NCS regenerations, and granular activated carbon replacement. Desludging, a major pain point for onsite sanitation systems, was unnecessary during the field trial and thereby not performed. The AnMBR performed well, removing 94.5 ± 5.0% of the influent COD across all three stages. The high COD removal rate is attributed to the sub-micron separation provided by the ultrafiltration membrane. The NCS was highly efficient at removing total nitrogen, residual COD and color, but the regeneration process was lengthy and is a topic of ongoing research. The EC provided effective disinfection, but frequent prolonged run cycles due to power supply and water quality issues upstream limited the overall system hydraulic throughput. This extended field trial under actual ambient conditions successfully demonstrated the feasibility of using advanced NSSS to address the global water and sanitation crises.

New Multi-Walled carbon nanotube of industrial interest induce cell death in murine fibroblast cells.

The search for new nanomaterials has brought to the multifactorial industry several opportunities for use and applications for existing materials. Carbon nanotubes (CNT), for example, present excellent properties which allow us to assume a series of applications, however there is concern in the industrial scope about possible adverse health effects related to constant exposure for inhalation or direct skin contact. Thus, using cell models is the fastest and safest way to assess the effects of a new material. The aim of this study was to investigate the cytotoxic profile in LA9 murine fibroblast lineage, of a new multi-walled carbon nanotube (MWCNT) that was functionalized with tetraethylenepentamine (TEPA) to obtain better physical-chemical characteristics for industrial use. The modifications presented in the CNT cause concern, as they can change its initial characteristics, making this nanomaterial harmful. HR-TEM, FE-SEM and zeta potential were used for the characterization. Cytotoxicity and cell proliferation tests, oxidative and nitrosative stress analyzes and inflammatory cytokine assay (TNF-α) were performed. The main findings demonstrated a reduction in cell viability, increased release of intracellular ROS, accompanied by an increase in TNF-α, indicating an important inflammatory profile. Confirmation of the data was performed by flow cytometry and ImageXpress with apoptosis/necrosis markers. These data provide initial evidence that OCNT-TEPA has a cytotoxic profile dependent on the concentration of LA9 fibroblasts, since there was an increase in free radicals, inflammation induction and cell death, suggesting that continuous exposure to this nanoparticle can cause damage to different tissues in the organism.

Maternal BMI at the time of birth and selected risk factors associated with severe neonatal outcomes: a secondary analysis of the WHO Better Outcomes in Labour Difficulty (BOLD) project.

The main objective of this secondary analysis was to describe the nutritional status of the Better Outcomes in Labour Difficulty (BOLD) project study population and determine possible associations between maternal nutritional status (as reflected by maternal BMI at the time of birth) and severe neonatal outcomes (SNO). We also analysed previous and index maternal pathologies to determine associations with neonatal outcomes. We used the classification designed by Atalah for maternal BMI and compared with the Hyperglycaemia and Adverse Pregnancy Outcome study one. To describe the nutritional status of this population, figures of distribution and test of normality related to weight and BMI were presented for the women and their babies. To explore the association between maternal BMI data and SNO, the χ2 test was performed. To identify a maternal characteristic or a group of characteristics that could predict SNO, we used Fisher's exact test using previous maternal pathology collected in the BOLD project as well as that in the index pregnancy. In this study, BMI at the time of birth was not associated with neonatal near miss or death. We found that previous maternal obesity, diabetes and chronic hypertension were associated with SNO. Maternal pathology in the index pregnancy such as other obstetric haemorrhage, pre-eclampsia, anaemia and gestational diabetes was associated with SNO.

Beyond too little, too late and too much, too soon: a pathway towards evidence-based, respectful maternity care worldwide.

On the continuum of maternal health care, two extreme situations exist: too little, too late (TLTL) and too much, too soon (TMTS). TLTL describes care with inadequate resources, below evidence-based standards, or care withheld or unavailable until too late to help. TLTL is an underlying problem associated with high maternal mortality and morbidity. TMTS describes the routine over-medicalisation of normal pregnancy and birth. TMTS includes unnecessary use of non-evidence-based interventions, as well as use of interventions that can be life saving when used appropriately, but harmful when applied routinely or overused. As facility births increase, so does the recognition that TMTS causes harm and increases health costs, and often concentrates disrespect and abuse. Although TMTS is typically ascribed to high-income countries and TLTL to low-income and middle-income ones, social and health inequities mean these extremes coexist in many countries. A global approach to quality and equitable maternal health, supporting the implementation of respectful, evidence-based care for all, is urgently needed. We present a systematic review of evidence-based clinical practice guidelines for routine antenatal, intrapartum, and postnatal care, categorising them as recommended, recommended only for clinical indications, and not recommended. We also present prevalence data from middle-income countries for specific clinical practices, which demonstrate TLTL and increasing TMTS. Health-care providers and health systems need to ensure that all women receive high-quality, evidence-based, equitable and respectful care. The right amount of care needs to be offered at the right time, and delivered in a manner that respects, protects, and promotes human rights.

Experimental type 2 diabetes induction reduces serum vaspin, but not serum omentin, in Wistar rats.

Vaspin and omentin are adipose tissue adipokines that have often been related to obesity and its comorbidities. The aim of this study was to investigate the behaviour of serum omentin and vaspin in models of type 2 diabetes. To do this, Wistar rats (~200 g) were randomly divided into two groups: a non-diabetic group (n = 6) and a diabetic group fed on a high-fat diet (n = 6) and a low dose of streptozotocin (Sigma® ). All procedures were approved by the Brazilian Ethics Committee. Body weight (BW) and food intake were recorded daily. Tail blood glucose levels were assessed at the end of the diabetes induction period. The insulin tolerance test (ITT) was performed after the diabetes induction period (7 weeks). The serum and tissues (liver, pancreas, and retroperitoneal (RET), epididymal (EPI) and visceral (VIS) white adipose tissues) were immediately removed and weighed. Analyses of levels of insulin, omentin, vaspin, adiponectin and inflammatory cytokines IL-6, IL-8 (CXCL8), TNF-α and C-reactive protein (CRP) in serum were performed using the enzyme-linked immunosorbent assay (ELISA). Our results showed that IL-8 and CRP serum levels in the diabetic group were significantly higher than in the non-diabetic group. Vaspin and adiponectin values were lower for the diabetic group than for the non-diabetic group. Omentin, IL-6 and TNF-α values did not differ between the groups. Our results showed that both the metabolism of the adipose tissue and the secretion of adipokines may be affected in diabetic rats. Omentin showed no difference between the groups, although the vaspin values decreased in the diabetic group.

Increases in Caesarean Delivery Rates and Change of Perinatal Outcomes in Low- and Middle-Income Countries: A Hospital-Level Analysis of Two WHO Surveys.

BACKGROUND: Maternal and neonatal outcomes have improved substantially. During the same period, the caesarean delivery rate soared. The aim of this analysis was to determine whether an increase in caesarean rate was associated with an improvement in perinatal outcome at an institutional level in low- and middle-income countries. METHODS: The WHO Global Survey on Maternal and Perinatal Health (WHOGS) and the WHO Multi-Country Survey on Maternal and Newborn Health (WHOMCS) were two multi-country, facility-based, cross-sectional surveys conducted in 2004-08 and 2010-11, respectively. The increase in caesarean rate and the change of prevalence of adverse perinatal outcomes were calculated using a two-point estimator of percent change annualized (PCA) method. Maternal, perinatal, and neonatal composite indexes were used as the outcomes. A linear mixed model was used to assess the association between the change of caesarean rate and the change of perinatal outcome. RESULTS: A total of 259 facilities in 20 countries participated in both surveys, with 217 844 women in WHOGS and 227 734 women in WHOMCS. The caesarean rate in these facilities increased, on average, by 4.0% annually, while the prevalence of adverse perinatal outcomes decreased by 4.6% annually. However, after adjustments for potential confounders, no association was found between the increase in caesarean rate and the change of adverse outcome indexes, regardless of whether starting caesarean rates were already high (above 10%) or not. CONCLUSIONS: In low- and middle-income countries, the increases in caesarean rates were not associated with improved perinatal outcomes regardless of whether the starting caesarean rate was already high or not.

Light-emitting diode modulates carbohydrate metabolism by pancreatic duct regeneration.

Pancreatic lesions can produce metabolic disorders. Light-emitting diode (LED) has been used as a safe and effective phototherapy for cell proliferation and regeneration. We investigate the effects of phototherapy using LED irradiation on the pancreas after the injection of streptozotocin (STZ) to induce experimental diabetes and evaluate that the ß cells can regenerate in the pancreas in an in vivo model and observe its implications on the control of carbohydrate metabolism. Twenty Wistar rats were randomized into three groups: non-diabetic control, diabetic control, and diabetic treated with LED. Except for the non-diabetic control group, all were induced to diabetes type I by streptozotocin injection. Treated groups were irradiated by LED: λ = 805 nm; 40 mW, 22 s; spot diameter 5 mm, spot area 0.196 cm2, 0.88 J that it was applied on pancreas projection area for 5 consecutive days and monitored for 30 days. Diabetic group treated with LED showed regeneration of islets and ducts (p = 0.001) on the pancreas. Intraperitoneal insulin tolerance test showed differences between the diabetic control and diabetic treated groups (p = 0.03). In diabetic control group, the hepatic glycogen content was 296% lower when compared with diabetic treated with LED. Furthermore, in the diabetic control group, the glycogen content of the gastrocnemius muscle was 706% smaller when compared with diabetic treated with LED. This study shows that LED was able to modify morphological and metabolic features and also altered carbohydrate metabolism on irradiated pancreas in experimental model of diabetes.

A pilot study combining Go4Life® materials with an interactive voice response system to promote physical activity in older women.

Telephone-based interactive voice response (IVR) systems could be an effective tool for promotion of physical activity among older women. To test IVR feasibility, we enrolled 30 older women in a 10-week physical activity intervention designed around National Institute on Aging (NIA) Go4Life® educational materials with IVR coaching. Participants (mean age = 76 years) significantly increased physical activity by a mean 79 ± 116 (SD) minutes/week (p < .001). Participants reported that the Go4Life® materials, pedometer, and IVR coaching (70% reported easy technology) were useful tools for change. This pilot study demonstrates IVR acceptability as an evidence-based physical activity program for older women.

Cyclo-oxygenase (COX) inhibitors for treating preterm labour.

BACKGROUND: Preterm birth is a major cause of perinatal mortality and morbidity. Cyclo-oxygenase (COX) inhibitors inhibit uterine contractions, are easily administered and appear to have few maternal side effects. However, adverse effects have been reported in the fetus and newborn as a result of exposure to COX inhibitors. OBJECTIVES: To assess the effects on maternal and neonatal outcomes of COX inhibitors administered as a tocolytic agent to women in preterm labour when compared with (i) placebo or no intervention and (ii) other tocolytics. In addition, to compare the effects of non-selective COX inhibitors with COX-2 selective inhibitors. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (24 August 2014). We also contacted recognised experts and searched reference lists of retrieved studies. SELECTION CRITERIA: All published and unpublished randomised trials in which COX inhibitors were used for tocolysis for women in labour between 20 and 36 completed weeks' gestation. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated methodological quality and extracted data. We sought additional information from study authors. Results are presented using risk ratio (RR; dichotomous data) and mean difference (MD; continuous data) with 95% confidence interval (CI). The number needed to treat for benefit (NNTB) and the number needed to treat for harm (NNTH) were calculated for statistically different categorical outcomes. MAIN RESULTS: With the addition of seven studies with a total of 684 women, this review now includes outcome data from 20 studies including 1509 women. The non-selective COX inhibitor indomethacin was used in 15 studies. The overall quality of the included studies was considered moderate to low.Three small studies (102 women), two of which were conducted in the 1980's, compared COX inhibition (indomethacin only) with placebo. No difference was shown in birth less than 48 hours after trial entry (average RR 0.20, 95% CI 0.03 to 1.28; two studies with 70 women). Indomethacin resulted in a reduction in preterm birth (before completion of 37 weeks of gestation) in one small study (36 women) (RR 0.21, 95% CI 0.07 to 0.62; NNTB 2, 95% CI 2 to 4); and an increase in gestational age at birth (average MD 3.59 weeks, 95% CI 0.65 to 6.52; two studies with 66 women) and birthweight (MD 716.34 g, 95% CI 425.52 to 1007.16; two studies with 67 infants). No difference was shown in measures of neonatal morbidity or neonatal mortality.Compared with betamimetics, COX inhibitors resulted in a reduction in birth less than 48 hours after trial entry (RR 0.27, 95% CI 0.08 to 0.96; NNTB 7, 95% CI 6 to 120; two studies with 100 women) and preterm birth (before completion of 37 weeks of gestation) (RR 0.53, 95% CI 0.28 to 0.99; NNTB 6, 95% CI 4 to 236; two studies with 80 women) although no benefit was shown in terms of neonatal morbidity or mortality. COX inhibition was also associated with fewer maternal adverse affects compared with betamimetics (RR 0.19, 95% CI 0.11 to 0.31; NNTB 3, 95% CI 2 to 3; five studies with 248 women) and maternal adverse effects requiring cessation of treatment (average RR 0.09, 95% CI 0.02 to 0.49; NNTB 5, CI 95% 5 to 9; three studies with 166 women).No differences were shown when comparing COX inhibitors with magnesium sulphate (MgSO4) (seven studies with 792 women) or calcium channel blockers (CCBs) (two studies with 230 women) in terms of prolonging pregnancy or for any fetal/neonatal outcomes. There were also no differences in very preterm birth (before completion of 34 weeks of gestation) and no maternal deaths occurred in the one study that reported on this outcome. However COX inhibitors resulted in fewer maternal adverse affects when compared with MgSO4 (RR 0.39, 95% CI 0.25 to 0.62; NNTB 11, 95% CI 9 to 17; five studies with 635 women).A comparison of non-selective COX inhibitors versus any COX-2 inhibitor (two studies with 54 women) did not demonstrate any differences in maternal, fetal or neonatal outcomes.No data were available to assess COX inhibitors compared with oxytocin receptor antagonists (ORAs). Further, no data were available on extremely preterm birth (before 28 weeks of gestation), longer-term infant outcomes or costs. AUTHORS' CONCLUSIONS: In this review, no clear benefit for COX inhibitors was shown over placebo or any other tocolytic agents. While some benefit was demonstrated in terms of postponement of birth for COX inhibitors over placebo and betamimetics and also maternal adverse effects over betamimetics and MgSO4, due to the limitations of small numbers, minimal data on safety, lack of longer-term outcomes and generally low quality of the studies included in this review, we conclude that there is insufficient evidence on which to base decisions about the role of COX inhibition for women in preterm labour. Further well-designed tocolytic studies are required to determine short- and longer-term infant benefit of COX inhibitors over placebo and other tocolytics, particularly CCBs and ORAs. Another important focus for future studies is identifying whether COX-2 inhibitors are superior to non-selective COX inhibitors. All future studies on tocolytics for women in preterm labour should assess longer-term effects into early childhood and also costs.

Neonatal near miss: a systematic review.

BACKGROUND: The concept of neonatal near miss has been proposed as a tool for assessment of quality of care in neonates who suffered any life-threatening condition. However, there are no internationally agreed concepts or criteria for defining or identifying neonatal near miss. The purpose of this study was to perform a systematic review of studies and markers that are able to identify neonatal near miss cases and predict neonatal mortality. METHODS: Electronic searches were performed in the Medline, Embase and Scielo databases, with no time or language restriction, until December 2014. The term "neonatal near miss" was used alone or in combination with terms related to neonatal morbidity/mortality and neonatal severity scores. Study selection criteria involved three steps: title, abstract and full text of the articles. Two researchers performed study selection and data extraction independently. Heterogeneity of study results did not permit the performance of meta-analysis. RESULTS: Following the inclusion and exclusion criteria adopted, only four articles were selected. Preterm and perinatal asphyxia were used as near miss markers in all studies. Health indicators on neonatal morbidity and mortality were extracted or estimated. The neonatal near miss rate was 2.6 to 8 times higher than the neonatal mortality rate. CONCLUSIONS: Pragmatic and management criteria are used to help develop the neonatal near miss concept. The most severe cases are identified and mortality is predicted with these criteria. Furthermore, the near miss concept can be used as a tool for evaluating neonatal care. It is the first step in building management strategies to reduce mortality and long-term sequelae.

Searching for the definition of macrosomia through an outcome-based approach in low- and middle-income countries: a secondary analysis of the WHO Global Survey in Africa, Asia and Latin America.

BACKGROUND: No consensus definition of macrosomia currently exists among researchers and obstetricians. We aimed to identify a definition of macrosomia that is more predictive of maternal and perinatal mortality and morbidity in low- and middle-income countries. METHODS: We conducted a secondary data analysis using WHO Global Survey on Maternal and Perinatal Health data on Africa and Latin America from 2004 to 2005 and Asia from 2007 to 2008. We compared adverse outcomes, which were assessed by the composite maternal mortality and morbidity index (MMMI) and perinatal mortality and morbidity index (PMMI) in subgroups with birthweight (3000-3499 g [reference group], 3500-3999 g, 4000-4099 g, 4100-4199 g, 4200-4299 g, 4300-4399 g, 4400-4499 g, 4500-4999 g) or country-specific birthweight percentile for gestational age (50(th)-74(th) percentile [reference group], 75(th)-89(th), 90(th)-94(th), 95(th)-96(th), and ≥97(th) percentile). Two-level logistic regression models were used to estimate odds ratios of MMMI and PMMI. RESULTS: A total of 246,659 singleton term births from 363 facilities in 23 low- and middle-income countries were included. Adjusted odds ratios (aORs) for intrapartum caesarean sections exceeded 2.0 when birthweight was greater than 4000 g (2·00 [95% CI: 1·68, 2·39], 2·42 [95% CI: 2·02, 2·89], 2·01 [95% CI: 1·74, 2·33] in Africa, Asia and Latin America, respectively). aORs of MMMI reached 2.0 when birthweight was greater than 4000 g, 4500 g in Asia and Africa, respectively. aORs of PMMI approached to 2.0 (1·78 [95% CI: 1·16, 2·74]) when birthweight was greater than 4500 g in Latin America. When birthweight was at the 90(th) percentile or higher, aORs of MMMI and PMMI increased, but none exceeded 2.0. CONCLUSIONS: The population-specific definition of macrosomia using birthweight cut-off points irrespective of gestational age (4500 g in Africa and Latin America, 4000 g in Asia) is more predictive of maternal and perinatal adverse outcomes, and simpler to apply compared to the definition based on birthweight percentile for a given gestational age.