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.

LP-211, a selective 5-HT7 receptor agonist, increases novelty-preference and promotes risk-prone behavior in rats.

Gambling disorder is associated to an increased impulsivity, a high level of novelty-seeking and a dysregulation of the forebrain neurotransmission systems. However, the neurobiological mechanisms of this addictive disorder are not fully understood and no valid pharmacological approach has yet been approved. The present study aimed to investigate the effect of 5-HT7 receptor (5-HT7 R) stimulation with a brain penetrant and selective agonist, LP-211 (0.25 and 0.50 mg kg-1 i.p.) during post-experience consolidation, (i) acutely in a novelty-preference test (Exp. 1) or (ii) sub-chronically in the Probabilistic-Delivery Task (rPDT, commonly used to measure individual differences in risk proneness of rats; Exp. 2). Results of Exp. 1 showed that 5-HT7 R activation improves consolidation of chamber-shape memory in the novelty-preference test, leading to significant novelty-induced hyperactivity and recognition, in conditions where controls displayed a null-preference. These results suggest that 5-HT7 Rs may be involved in the consolidation of information inherent to spatial environments, facilitating the recognition of novelty. Furthermore, in the operant rPDT (Exp. 2), 5-HT7 R activation shifts the choice towards a larger yet unlikely reward and turns the propensity of rats towards risk-prone behavior. Thus, 5-HT7 Rs stimulation apparently strengthens the consideration of future, bigger rewards, also enhancing the seeking of it by operant pokes. These effects may well be explained by LP-211 actions on hippocampal versus prefrontal cortex-mediated regulations, leading to improved (though suboptimal) strategy formation. However, further experiments are necessary to determine more in depth the serotonergic pathways involved.

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.

Medication-related osteonecrosis of the jaw associated with bisphosphonates and denosumab in osteoporosis.

OBJECTIVE: To describe the clinical characteristics and evolution of our series of medication-related osteonecrosis of the jaws (MRONJ) associated with denosumab in osteoporotic patients. MATERIAL AND METHODS: We present 10 new cases of MRONJ in patients receiving denosumab for osteoporosis. We describe the mean doses of denosumab, previous bisphosphonate intake, and the clinical characteristics associated with the osteonecrosis, such as local contributing factors, symptoms, and evolution after treatment. RESULTS: The mean number of denosumab doses was 3.4 ± 2.2. In 90% of patients, there was a prior history of oral bisphosphonate intake, with a mean duration of 46.78 ± 25.11 months. The most common local factor was dental extraction (6 cases; 60%), and most cases had necrotic bone exposure (9/10, 90%). Sclerosis of the bone was the most common radiographic finding. Stage 1 was the most common ONM stage, found in 80%. 'Cure' after conservative treatments was obtained in 71.4%. CONCLUSIONS: Most of our cases were in the early stages of MRONJ, and the success rate after conservative treatment was high.

The efficacy of prophylactic IVC filters in gastric bypass surgery.

BACKGROUND: Patients undergoing gastric bypass surgery have a high risk for thromboembolic events. Over the last decade, the use of prophylactic IVC filters (IVCF) has drastically increased for patients who are considered high risk. However, the role and efficacy of prophylactic IVCF placement remain controversial, and the literature is limited to a few retrospective studies. METHODS: We conducted a systematic review of the literature. A total of 21 articles were analyzed, and eight relevant retrospective studies were chosen for review of data. Data from laparoscopic gastric bypass surgery were compared to open gastric bypass surgery RESULTS: The relevant eight retrospective studies included a total of 597 patients. Patients had IVCFs before laparoscopic gastric bypass (41 %) and before open gastric bypass (59 %). There were 5 postoperative pulmonary emboli (PE) (0.84 %), 21 DVTs (3.52 %), 5 minor IVCF-related complications (0.84 %), 2 major IVCF-related complications (0.34 %), and 10 deaths (1.68 %). The rate of postoperative PE was the same in the laparoscopic group and the open group (0.84 %). The rate of DVT in the laparoscopic group was 5.02 %, and in the open group, it was 2.23 %. CONCLUSION: It is estimated that 55 % of bariatric surgeons use IVCF in high-risk patients. Prospective research that supports the use of IVCF is very limited, and individualized placement relies on retrospective studies only. In addition, patient characteristics associated with high risk vary between different studies. Our review showed that most of the published studies support the use of prophylactic IVCF and found it to be safe. On the other hand, the largest and most recent retrospective cohort study does not support their use. The efficacy of prophylactic IVCFs before gastric bypass surgery in high-risk patients has not been established.

Comparison of vitrification and conventional freezing for cryopreservation of caprine embryos.

The experiment aimed to compare conventional freezing and different vitrification protocols for cryopreservation of caprine embryos at morphological, ultrastructural, and functional levels. Caprine embryos produced in vivo were allocated randomly to three groups: (1) conventional freezing with ethylene glycol (EG); (2) dimethyl sulfoxide + EG (DMSO/EG) vitrification; and (3) dimethylformamide + EG (DMF/EG) vitrification. All groups were scored for cell viability (propidium iodide staining and ultrastructural levels) and re-expansion rate after thawing or warming. Embryos subjected to DMSO/EG vitrification showed higher cell viability (73.33%), compared with DMF/EG vitrification and conventional freezing group embryos (40.00 and 66.66%, respectively). The ultrastructural study revealed that vitrified embryos had greater preservation of cellular structure than embryos from conventional freezing with EG. DMSO/EG vitrification resulted in higher rates of re-expansion in vitro (47.36%) than DMF/EG vitrification (31.58%), and conventional freezing (25.00%). In conclusion, caprine embryos produced in vivo are better cryopreserved after vitrification than conventional freezing, therefore we conclude that DMSO/EG vitrification is the most effective protocol for cryopreservation.

The 100-year evolution of the isolated internal iliac artery aneurysm.

BACKGROUND: Isolated internal iliac artery aneurysms (IIIAA) are a rare form of aneurysm. The incidence increases with age, and the prevalence is higher in men. The clinical presentation can vary, and standard treatment protocols are not established. The first case of an IIIAA was described more than 100 years ago. The purpose of the study is to summarize the various clinical presentations and treatment options that have been reported in the literature in the past 100 years. METHODS: Literature about IIIAA was reviewed using the electronic databank PubMed. All case reports and case series were analyzed, and we included our own data with 2 case reports. RESULTS: Over time, IIIAA diagnosis increasingly resulted from asymptomatic incidental findings on radiologic studies. Various clinical presentations included abdominal pain, back pain, rectal bleeding, hydronephrosis with renal failure, hematuria, and free rupture with shock. Rupture has a mortality rate of 53%. IIIAAs were more common on the left (61.8% left, 27.3% right, 10.9% bilateral). Treatments include open surgical repair and endovascular repair using a variety of methods. One article reported a hybrid method using both endovascular and open surgical technique. CONCLUSIONS: Since its first description 100 years ago, we have gained knowledge about the natural history of IIIAA. Multiple treatment options have been described, but long-term outcome needs further investigation.

First collection records of Culiseta (Culicella) nipponica in the Republic of Korea.

The 1st confirmed record of Culiseta nipponica for the Republic of Korea was made at Osan Air Base and Tongilchon, Gyeonggi Province, and at the Incheon International Airport, Incheon metropolitan area, using carbon dioxide-baited light and Mosquito Magnet traps. Larval surveys near adult collection sites during June and August 2013 were negative for Culiseta nipponica.

A pictorial key to the species of Aedes (Ochlerotatus and Coetzeemyia) in the Afrotropical Region (Diptera: Culicidae).

Six species of the subgenus Ochlerotatus and one species of the subgenus Coetzeemyia of the genus Aedes in the Afrotropical Region are treated in a pictorial key based on diagnostic morphological features. Brief remarks on the new reclassification of the genus Aedes are also included.

A new species of the genus Orthopodomyia from Ototomo, Cameroon, with notes on other Orthopodomyia group-species.

A new species belonging to the new Ototomoensis Group, Orthopodomyia ototomoensis Huang and Rueda, is described from Ototomo, Cameroon. Diagnostic features for separating members of Nkolbissonensis Group and Ototomoensis Group from other Orthopodomyia groups are provided. Two supplemental keys are presented: "A Pictorial Key to the Species of the Genus Orthopodomyia Ototomoensis Group in the Afrotropical Region (Diptera: Culicidae)" and "A Pictorial Key to the Species of the Genus Orthopodomyia Nkolbissonensis Group in the Afrotropical Region (Diptera: Culicidae)".

Malaria vectors in the Greater Mekong Subregion: overview of malaria vectors and remaining challenges.

Malaria transmission in the Greater Mekong Subregion depends on, among other factors, vector behavior and ecology, and the degree of contact between humans and the Anopheles mosquitoes. This chapter will review and update knowledge presented in the 2003 Mekong Malaria monograph for planning and implementing evidence-based vector control programs. Collation of 150 publications and reports showed that the highest number of vector species reported included An. minimus Theobald complex (26.74%), An. dirus Peyton and Harrison (14.26%), An. sundaicus (Rodenwaldt) (5.65%), An. sinensis Wiedemann (4.29%), An. maculatus Theobald (4.23%), An. philippinensis Ludlow (1.62%), An. annularis Van der Wulp (0.37%), An. campestris Reid (0.25%), and An. lesteri Baisas and Hu (=anthropophagus) (0.045%). Other Anopheles species accounted for 44.44%. Anopheles dirus was incriminated as a vector of Plasmodium knowlesi malaria in Viet Nam for the first time, but remained a suspected simian vector in other countries in the region. Well-designed trials of innovative strategies in intractable and difficult situations are needed, including a better understanding of the various causal relations and interactions between physiology, environment, and vector bionomics. While current front-line vector control interventions have contributed significantly to a worldwide decrease of malaria, indoor residual spraying and insecticide-treated bednets/ long lasting insecticidal bednets have had variable impact on exophilic/exophagic and/or early biting vectors. As vectors' responses to control measures vary in different areas, entomological studies on the efficacy of insecticide-treated bednets and other innovative control tools to ensure that strategies are tailored to local circumstances. Given that current tools are insufficient to break transmission cycles, more strategic investments into research on outdoor transmission, monitoring of insecticide resistance, vector species identities, vector mapping, target profiles of new control technologies and delivery systems are required.

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.

Mosquito bisection as a variable in estimates of PCR-derived malaria sporozoite rates.

BACKGROUND: Highly sensitive polymerase chain reaction (PCR) methods offer an alternative to the light microscopy examination of mosquito salivary glands for the determination of malaria sporozoite rates in wild caught female Anopheles. Removal of mosquito abdomens is assumed to eliminate false positives caused by malaria oocyst DNA in the midgut. This assumption has not been tested with current gold standard PCR assays, and for the variety of conditions that specimens could encounter in the laboratory and field. METHODS: Laboratory Anopheles stephensi were used that had been infected with Plasmodium falciparum 6-7 days and 14 days post infection (p.i.), when oocysts only and oocysts + sporozoites, respectively, are developed. Mosquitoes were killed and immediately frozen, air dried before being frozen, or stored under humid conditions overnight before being frozen, to simulate a range of conditions in the field. Additionally, abdomens were removed anterior to, at, or posterior to the junction of the abdomen and thorax, and both portions were processed using a standard nested PCR of the small sub-unit nuclear ribosomal genes (ssrDNA) with products visualized on agarose gels. RESULTS: Overall, 4.1 % (4/97) of head + thorax samples that were 6-7 days p.i. gave apparent false positives for sporozoites, compared to 9.3 % (9/97) that were positive for abdomens. No positives (0/52) were obtained when similar specimens were bisected anterior to the junction of the thorax and abdomen, compared to 21.2 % (11/52) that were positive for posterior portions. Multiple bands were noted for positives from the 'Frozen' treatment and the rate of false negatives due to DNA degradation appears higher under the 'Humid' treatment. Reproducibility of results for the 'Frozen' treatment was 90 %. CONCLUSIONS: Despite the importance of specimen condition and the bisection step in determining sporozoite rates, little attention has been paid to them in the literature. Recommendations from this study are that: 1) care needs to be taken to reduce DNA degradation in the field; 2) mosquito abdomens be separated anterior to the junction of the thorax and abdomen; and 3) DNA sequencing of a subsample of positive results should be undertaken if possible.

Mosquito fauna of Ubin Island, Singapore.

We report the mosquito species and their distribution records for Ubin Island, Singapore, based on our field collections in February 2010, routine adult and larval surveys from 1993 to 2009 by Singapore operational officers, and accessioned specimens deposited in the Environmental Health Institute, Singapore, and the US National Museum of Natural History, Washington, DC. A total of 25 species and 6 unidentified species belonging to 9 genera (Aedes, Anopheles, Armigeres, Coquillettidia, Culex, Lutzia, Mansonia, Uranotaenia, and Verrallina) were identified and recorded from Ubin Island, based on specimens collected from 1993 to 2010.

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).

Endovascular treatment of symptomatic pulmonary sequestration.

Pulmonary sequestration is a rare congenital malformation whose origin is bronchial and arterial simultaneously and its vascularization comes from an anomalous systemic artery. Its clinical presentation includes recurrent pneumopathy in the same anatomic location of the lung and difficult to resolve or recurrent lung abscess. It is usually treated with antibiotherapy and eventual surgical resection. A 23-year-old woman with history of recurrent respiratory infections and three episodes of hemoptysis was admitted at the hospital. Computed tomography and magnetic resonance imaging confirmed diagnosis of pulmonary sequestration. The angiographic study showed the presence of three inflow arteries arising from the thoracic aorta (T10) and supplying the abnormal lung parenchyma at the base of the left hemithorax. The patient underwent endovascular treatment consisting of exclusion of the inflow vessels with Amplatzer occlusive devices and coils. Subsequent computed tomography angiogram confirmed complete infarction of the sequestration. At 7 months, the patient presented with a new episode of bronchial infection. Repeated angiography showed persistence of intermediate small nutrient branches that were treated with coil embolization. The patient is symptom-free at 41 months after this secondary procedure. Endovascular treatment of pulmonary sequestration, with selective embolization of the inflow arteries, is a very attractive minimally invasive therapeutic option, as compared with conventional surgery, and potentially less prone to associated complications.

The AFHSC-Division of GEIS Operations Predictive Surveillance Program: a multidisciplinary approach for the early detection and response to disease outbreaks.

The Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System Operations (AFHSC-GEIS) initiated a coordinated, multidisciplinary program to link data sets and information derived from eco-climatic remote sensing activities, ecologic niche modeling, arthropod vector, animal disease-host/reservoir, and human disease surveillance for febrile illnesses, into a predictive surveillance program that generates advisories and alerts on emerging infectious disease outbreaks. The program's ultimate goal is pro-active public health practice through pre-event preparedness, prevention and control, and response decision-making and prioritization. This multidisciplinary program is rooted in over 10 years experience in predictive surveillance for Rift Valley fever outbreaks in Eastern Africa. The AFHSC-GEIS Rift Valley fever project is based on the identification and use of disease-emergence critical detection points as reliable signals for increased outbreak risk. The AFHSC-GEIS predictive surveillance program has formalized the Rift Valley fever project into a structured template for extending predictive surveillance capability to other Department of Defense (DoD)-priority vector- and water-borne, and zoonotic diseases and geographic areas. These include leishmaniasis, malaria, and Crimea-Congo and other viral hemorrhagic fevers in Central Asia and Africa, dengue fever in Asia and the Americas, Japanese encephalitis (JE) and chikungunya fever in Asia, and rickettsial and other tick-borne infections in the U.S., Africa and Asia.

Mosquito species composition and Plasmodium vivax infection rates on Baengnyeong-do (island), Republic of Korea.

Vivax malaria is a significant military and civilian health threat in the north of the Republic of Korea (ROK). The island of Baengnyeong-do is the westernmost point of the ROK and is located close to the southwestern coast of the Democratic People's Republic of Korea (DPRK). Mosquitoes were collected using a black light trap on Baengnyeong-do, and Anopheles spp. were assayed by PCR, to identify the species, and screened for sporozoites of Plasmodium vivax. Of a subsample of 257 mosquitoes, Anopheles lesteri was the most frequently collected (49.8%), followed by Anopheles sinensis (22.6%), Anopheles pullus (18.7%), Anopheles kleini (7.8%), and Anopheles belenrae (1.2%). The overall sporozoite rate was 3.1%, with the highest rates observed in An. kleini (15.0%), An. sinensis (5.2%), and An. lesteri (1.6%). No sporozoite positive An. pullus or An. belenrae were observed. The results extend our knowledge of the distribution and potential role in malaria transmission of An. kleini, An. lesteri, and An. sinensis, for an area previously considered to be at a low risk for contracting vivax malaria.