Early Penetration Research Articles

Hereditary transthyretin amyloidosis caused by Val142Ile variant in Spain: phenotypic characteristics, geographic distribution and population frequency

Abstract Background During recent years, several cases of hereditary transthyretin amyloidosis (ATTRv) due to p.Val142Ile have been described in patients without African ancestry in countries like Japan, Spain or Italy (1,2,3,4). All this evidence suggests that p.Val142Ile might be more prevalent than expected worldwide. Objectives The aim of this study was to analyze the impact of ATTRv caused p.Val142Ile in Spain to define its phenotypic characteristics, to explore endemic geographical areas and define its population frequency. Methods Patients diagnosed with ATTRv caused by p.Val142Ile and carriers irrespective of their phenotype were recruited from 16 centers in Spain. Baseline characteristics and events during follow-up were retrieved. Population frequency was assessed through the Spanish National DNA bank (N=3,569) and the Catalan Health Databank (N=790). Results The cohort included information regarding 164 subjects (75 probands [45.7%] and 89 relatives [54.3%]). Among probands, mean age was 73.9 ± 8.5 years and 47 (62.7%) were males. 67 probands (89.3%) had self-declared European ancestry and only 6 cases (8%) referred African or Afro-American ancestry. Cardiac symptoms were the most frequent reason leading to ATTRv diagnosis (N=64, 85.3%) followed by incidental finding (N=8, 10.7%) and neurologic symptoms (N=3, 4%). (Figure 1). Median follow-up was 1.6 years (Interquartile range 0.6-3.2). Neurologic involvement was observed in 35 probands (46.7%) at first evaluation or during follow-up. Overall penetrance at 65, 75 and 85 years was 12.8%, 44.3% and 94.2% respectively. Male sex was associated with earlier penetrance than women (P = 0.02). 38 patients initiated treatment with tafamidis during follow-up (28 [73.7%] 20 mg and 10 [26.3%] 61 mg), despite treatment, disease progression at 1 year (cardiovascular death or 30% increase of NTProBNP) was observed in 10 patients (40%). Population frequency was estimated between 0.0% and 0.12% based on the Spanish and Catalan databases respectively. Birthplace of probands suggests a higher prevalence in the Mediterranean basin. (Figure 2) Conclusions Our data suggests that ATTRv caused by p.Val142Ile has a significant prevalence in Spain, mostly in some specific regions. Phenotypic features are defined by late onset, male predominance, and cardiac involvement although a significant proportion develop neuropathy. Disease progression was observed in 40% of patients despite disease-modifying therapies.

Satpuraphyllum furcatum—a new genus and species of Peltaspermales foliage from the mid-Permian Barakar Formation of India

Satpuraphyllum furcatum gen. et sp. nov. is introduced to accommodate once- to twice-forked leaves with slender entire-margined segments containing a midrib that gives off very acute, freely dichotomizing, secondary veins. The leaves are amphistomatic, bearing incompletely monocyclic to amphicyclic stomata and diverse trichomes, papillae, and sparse multicellular low domal glands. These collective characters favour assignment to Peltaspermales and this is supported by co-preservation, in the same beds, of leaves with shield-shaped bracts bearing marginal seed scars. Satpuraphyllum furcatum is documented from the upper Barakar Formation (Kungurian) of central India and is the oldest known peltasperm from the core regions of Gondwana. Its presence in the Satpura Basin at that time signifies an early penetration of Peltaspermales into the Southern Hemisphere, possibly during the Artinskian–Kungurian Warming Event (initiating ca 287 Ma). Deepa Agnihotri [ deepa_agnihotri@bsip.res.in ] Birbal Sahni Institute of Palaeosciences, 53 University Road, Lucknow-226007, India. AK Srivastava [ srivasatava019@gmail.com ] 5/595, Vikas Nagar, Lucknow, India. Stephen McLoughlin* [ steve.mcloughlin@nrm.se ] Department of Palaeobiology, Swedish Museum of Natural History, Box 50007, Stockholm, 10405, Sweden.

Cellular changes and PR-1 gene expression accompanying infection-related morphogenesis and cell progression during invasive growth Pyricularia oryzae pathotype Triticum in resistant and susceptible wheat cultivars

Pyricularia oryzae pathotype Triticum (PoT) causes Wheat Blast, a devastating crop disease present in many wheat-producing countries. With the aim to contribute with the understanding of the mechanisms underlying pathogenesis of the fungus on wheat (Triticum aestivum), cytological and molecular studies were performed here.Susceptible and resistant interactions of wheat-PoT in cultivars of different levels of resistance were investigated by cellular changes and the molecular responses of wheat leaves according PR-1 expression. There was significant difference between susceptible (Apogee-PY15-PY34, Buck, MSINTA-PY15) and resistant (Buck-PY34, MSINTA-PY34) interactions in the responses tested. The two isolates of PoT analysed showed different ability to infect wheat plants at the cellular level during early tissue penetration analysed and documented by epi-fluorescence microscopy, patterns of PR-1 genes, and wheat plant defense reaction.Microscopic time-course analysis (24, 48, 72 and 96 h after inoculation) of individual interaction sites per leaf revealed different leaf invasion strategies of the more and less aggressive PoT isolates during the first stages of the course of pathogenesis.The results and conclusions of the present study provides the first evidence that different PR-1 spatial and temporal expression patterns occur in the early infective process of wheat-PoT, underlying two different defence mechanisms in plants according susceptible or resistant interactions. Thus, the results here laid a theoretical foundation for the future control of wheat blast using the different pattern of PR-1 gene as markers for disease resistance during the first stages of infection providing a significant contribution to a more efficient selection of wheat genotypes in breeding studies.

Comparative secretome analysis of Striga and Cuscuta species identifies candidate virulence factors for two evolutionarily independent parasitic plant lineages

BackgroundMany parasitic plants of the genera Striga and Cuscuta inflict huge agricultural damage worldwide. To form and maintain a connection with a host plant, parasitic plants deploy virulence factors (VFs) that interact with host biology. They possess a secretome that represents the complement of proteins secreted from cells and like other plant parasites such as fungi, bacteria or nematodes, some secreted proteins represent VFs crucial to successful host colonisation. Understanding the genome-wide complement of putative secreted proteins from parasitic plants, and their expression during host invasion, will advance understanding of virulence mechanisms used by parasitic plants to suppress/evade host immune responses and to establish and maintain a parasite-host interaction.ResultsWe conducted a comparative analysis of the secretomes of root (Striga spp.) and shoot (Cuscuta spp.) parasitic plants, to enable prediction of candidate VFs. Using orthogroup clustering and protein domain analyses we identified gene families/functional annotations common to both Striga and Cuscuta species that were not present in their closest non-parasitic relatives (e.g. strictosidine synthase like enzymes), or specific to either the Striga or Cuscuta secretomes. For example, Striga secretomes were strongly associated with ‘PAR1’ protein domains. These were rare in the Cuscuta secretomes but an abundance of ‘GMC oxidoreductase’ domains were found, that were not present in the Striga secretomes. We then conducted transcriptional profiling of genes encoding putatively secreted proteins for the most agriculturally damaging root parasitic weed of cereals, S. hermonthica. A significant portion of the Striga-specific secretome set was differentially expressed during parasitism, which we probed further to identify genes following a ‘wave-like’ expression pattern peaking in the early penetration stage of infection. We identified 39 genes encoding putative VFs with functions such as cell wall modification, immune suppression, protease, kinase, or peroxidase activities, that are excellent candidates for future functional studies.ConclusionsOur study represents a comprehensive secretome analysis among parasitic plants and revealed both similarities and differences in candidate VFs between Striga and Cuscuta species. This knowledge is crucial for the development of new management strategies and delaying the evolution of virulence in parasitic weeds.

Северокавказцы в Османской империи до эпохи мухаджирства: формы проникновения и особенности интеграции/элитизации

The article is based on both published and unpublished Turkish sources and modern, mainly for-eign, historiography, examines the ways and channels of the early (pre-muhajir) penetration of ethnic North Caucasians into the Ottoman Empire and the features of their integration into local society. Particular attention is paid to elucidating the factors and mechanisms of the formation, reproduction and functioning of the Caucasian (Circassian, Abkhaz, West Georgian, Daghestani) elite groups and strata of slave and non-slave origin and their place in the structure of state power and social life of the Ottoman Empire in the classical and postclassical periods of its history. An attempt was made to examine the nature of this community’s ethnonational identity, which demonstrated a certain resistance to assimilation as well as the potential to maintain some aspects of its original cultural profile for an extended period of time. The involvement of Istanbul’s “Cir-cassian” elites in developing and implementing the Porte’s Caucasian policy, as well as launching the enormous exodus of highlanders from the Caucasus to the Ottoman Empire in the mid-19th century, appears insignificant.

Hardly Venus’s servant—morphological adaptations of Veneriserva to an endoparasitic lifestyle and its phylogenetic position within Dorvilleidae (Annelida)

Endoparasitic annelids living inside another annelid host are known, particularly with regard to Oenonidae, but in general are poorly studied. The dorvilleid Veneriserva pygoclava is known from southern California, and its genus name (Latin = Venus’s servant) alludes to the close association with the host aphroditid scaleworm Aphrodita longipalpa. Little is known on fundamental questions on the biology of Veneriserva pygoclava. What is its mode of reproduction? How do they feed? How do they penetrate the host? We have studied multiple parasitized hosts and V. pygoclava specimens, using an integrative approach, combining µCT, histology, and electron microscopy. 3D reconstructions from µCT data of a parasitized Aphrodita show the exact position of the parasites in their natural condition within the host’s coelomic cavity. Ultrastructural investigations of the parasites revealed interesting adaptations to their lifestyle such as the complete reduction of their gut, despite the presence of a functional jaw apparatus and a modified epidermis enabling nutrient uptake from the host’s coelomic fluid. In addition to these, we also investigated spermatogenesis and oogenesis in V. pygoclava. Sperm morphology indicates an external fertilization of eggs within the coelomic cavity of the host. Mature male and female parasites living inside the same mature host and the presence of juvenile V. pygoclava within juveniles of Aphrodita suggest an obligate form of parasitism with a very early penetration of the hosts. In addition to our detailed morphological investigation, we conducted a phylogenetic analysis showing the position of Veneriserva within Dorvilleidae and its position was recovered nested among taxa of the Iphitime. Our phylogenetic analyses also show that the taxation Ophryotrocha puerilis siberti should be given full species rank and referred to as Ophryotrocha siberti. Finally, we publish here the full mitochondrial genome of V. pygoclava and discuss its novel gene order with reference to other annelids.

Penetrating Keratoplasty in Congenital Glaucoma.

Childhood glaucoma is one of the most common causes of corneal opacity in childhood and is associated with various pathological corneal changes, including corneal enlargement, corneal clouding, and edema. Congenital glaucoma (CG) may cause a decrease in vision outcomes due to corneal opacity or clouding, which is often associated with stimulus deprivation amblyopia. Therefore, to create a balance between preventing amblyopia and sustaining corneal clearance, patients with CG can be managed with early penetrating corneal transplantation surgery along with advanced glaucoma management. To investigate the graft survival rate and factors affecting graft survival in patients with congenital glaucoma who underwent penetrating keratoplasty (PKP). Cross-sectional. Patients with congenital glaucoma who underwent PKP were retrospectively evaluated. The associations between age, corneal diameter, presence of ocular comorbidities, concurrent ocular surgeries with corneal graft, and visual outcomes were assessed. Among the 30 eyes enrolled in the study, 6 (20%) had aniridia, 6 (20%) had Axenfeld-Rieger syndrome, and 18 (60%) were diagnosed with primary congenital glaucoma. Graft survival rates were 66.6% and 63.33% at 12 and 24 months, respectively. At the end of the follow-up, the overall graft survival rate was 60%. Statistical significance was observed between patient age at the time of surgery and graft failure (p = 0.02). Graft failure was associated with a younger patient age. Functional vision was achieved in 53.3% of patients. The management of congenital glaucoma and its corneal complications is a delicate issue that requires great effort. PKP in congenital glaucoma was moderately successful in the present study. To provide functional vision, PKP could be the treatment of choice.

Development of High Durable Pore-Filling Anion Exchange Membranes for Water Electrolysis Application

Water electrolyzer is a device that converts renewable electrical energy into environmentally friendly chemical energy, hydrogen. Water electrolysis is mainly categorized into proton exchange membrane water electrolysis (PEMWE) and anion exchange membrane water electrolysis (AEMWE). Non-precious electrocatalysts and hydrocarbon-based polymeric membranes are used for two different systems. It is advantageous for AEMWE in terms of cost. However, low current density and chemical stability for current anion exchange membrane technology (AEM) restricts early market penetration. Thus, thedevelopment of low resistance and high durable AEMs is of importance. In this study, superior ion conductivity and high durable pore-filling AEMs were developed for AEMWE. Pore-filling AMEs with different contents of crosslinking monomers were prepared by the monomers using chemically stable anion exchangeable functional groups in a porous polyethylene(PE) substrate. Properties of the AEMs were characterized through areal resistance, ionic conductivity, ion exchange capacity, water uptake, swelling ratio, mechanical strength and hydrogen crossover. In addition, AEMWE performance and durability tests were also conducted. Acknowledgments This research was supported in part by Cooperative Research Program for Agriculture Science and Technology Development (Project No. PJ016253), Rural Development Administration, Republic of Korea and by 2021 Green Convergence Professional Manpower Training Program of the Korea Environmental Industry and Technology Institute funded by the Ministry of Environment.

Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study

BackgroundMYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene. ObjectivesThis study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies. MethodsIn this multicenter cohort study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients. ResultsIn total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age <12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95% CI: 1.15-3.04; P = 0.012) and at age ≤1 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95% CI: 4.81-93.20; P < 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95% CI: 1.09-5.50; P = 0.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95% CI: 1.15-2.87; P = 0.010) and at age ≤5 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95% CI: 5.16-291.88; P < 0.001). ConclusionsMYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at <12 years.

Do Conditional Cash Transfers Improve Economic Outcomes in the Next Generation? Evidence from Mexico

AbstractConditional cash transfer programmes have spread to over 60 countries in the past two decades, but little is known about their long-term effects. We estimate the lasting impact of childhood exposure to the Mexico’s flagship programme Progresa by leveraging the age structure of benefits and geographic variation in early programme penetration nationwide. Childhood exposure improves women’s outcomes in early adulthood with increases in educational attainment, geographic mobility, labour market performance and household living standards. For men, effects are smaller and more difficult to distinguish from spatial convergence.

Hypertrophic cardiomyopathy in purpose-bred cats with the A31P mutation in cardiac myosin binding protein-C

We sought to establish a large animal model of inherited hypertrophic cardiomyopathy (HCM) with sufficient disease severity and early penetrance for identification of novel therapeutic strategies. HCM is the most common inherited cardiac disorder affecting 1 in 250–500 people, yet few therapies for its treatment or prevention are available. A research colony of purpose-bred cats carrying the A31P mutation in MYBPC3 was founded using sperm from a single heterozygous male cat. Cardiac function in four generations was assessed by periodic echocardiography and measurement of blood biomarkers. Results showed that HCM penetrance was age-dependent, and that penetrance occurred earlier and was more severe in successive generations, especially in homozygotes. Homozygosity was also associated with progression from preclinical to clinical disease. A31P homozygous cats represent a heritable model of HCM with early disease penetrance and a severe phenotype necessary for interventional studies aimed at altering disease progression. The occurrence of a more severe phenotype in later generations of cats, and the occasional occurrence of HCM in wildtype cats suggests the presence of at least one gene modifier or a second causal variant in this research colony that exacerbates the HCM phenotype when inherited in combination with the A31P mutation.

The Case Files

Figure: CT scan of the head illustrating possible cribriform penetration.FigureFigureInitial symptoms of cerebritis are nonspecific, making it difficult to diagnose A 34-year-old man presented with a frontal headache and two syncopal episodes over 24 hours. The patient had had URI symptoms—sore throat, rhinorrhea, and mild shortness of breath—for three weeks. He had no history of headaches or fevers, he hadn't traveled recently, and he didn't use drugs or take any medications. The patient's first syncopal episode occurred a day earlier while at work. It happened suddenly, without any prodromal symptoms. He did not seek medical care, and he finished his shift. The second episode occurred at home suddenly, without any prodromal symptoms, and prompted him to go to the ED. The patient had normal vitals and was alert. His physical exam showed no abnormalities. Lab work was ordered, including CBC, CMP, ECG, chest x-ray, and head CT. The CT identified extensive paranasal sinus disease with penetration of the cribriform plate and a small epidural collection, raising concern for an epidural abscess or cerebritis. The patient was treated in the ED with IV fluids and broad-spectrum antibiotics, including vancomycin and piperacillin-tazobactam, and he was made NPO. ENT recommended the patient be transferred to a tertiary care center for ENT and neurosurgery consultation. An MRI showed extensive sinus disease without a frank intracranial abscess. The patient underwent nasal septoplasty, inferior turbinate submucous resection, left maxillary antrostomy with tissue removal, left frontal sinusotomy, and left total ethmoidectomy. The patient's headache improved significantly following the procedures, and he had no more episodes of syncope. Blood cultures revealed Bacillus species. He was transitioned off IV antibiotics and discharged with a seven-day course of amoxicillin and clavulanate at home after a four-day hospital course. This was a rare form of syncope brought on by extensive sinus disease with early penetration into the CNS. Cerebritis is inflammation of the cerebrum with nonspecific findings on CT scan. It develops in response to pyogenic bacteria, most commonly Staphylococcus and Streptococcus. This infection develops typically from otogenic and odontogenic sources, recent procedures, penetrating head trauma, or via hematogenous spread. It's difficult to diagnose cerebritis early because initial symptoms are nonspecific and patients do not present until late findings such as headache, altered mental status, syncope, and seizures are present. Labs may show leukocytosis, but that is also not specific. Diagnosis is made by imaging with CT or MRI. Acute treatment in the ED includes managing the patient's symptoms, NPO status, broad-spectrum antibiotics, and admission with ENT and neurosurgery consults. Syncope is a common presentation in the ED, but cerebritis as a cause is rarely seen. Prompt evaluation and management likely prevented further complications and progression of the disease.

LATE ARCHAIC BURIAL 470 FROM THE NECROPOLIS OF PHANAGORIA

As a result of the archaeological excavations of the Bosporus necropolises, anthropological collections have been collected and published over the years, giving an idea of the morphological type of ordinary rural and urban residents in different chronological periods. M. M. Gerasimova studied material from the necropolis of Phanagoria, which dates back to the III century BC — IV century AD. The series consists of 58 adult skulls (32 male, 24 female) and 2 children’s skull. The author concludes that the buried belonged to the Pontic variant of the Mediterranean race. The Hellenistic, Sarmatian and Sindo-Meotic components are distinguished, with the latter being predominant.&#x0D; The proposed publication is devoted to a find obtained from the necropolis of Phanagoria in 1988. A male skeleton (No. 470) was discovered on the southeastern outskirts of the settlement, among children’s burials, and was located in a ground pit with shoulder pads, rectangular in plan. The inventory consisted of a red clay amphora, a black-glazed kylix, an iron akinak dagger, an iron spearhead, a gray clay bowl, and a black-figure lekyph. The burial dates back to the last third of the VI — the first two decades of the V century BC and belonged, according to the author of the excavations O. A. Zavoykin, to a nobility. The deceased was buried at the age of 30—40. The skull is brachycranic, with a wide, medium-high face, has large longitudinal and transverse diameters and a rather powerful bone structure. The significant flattening of the facial area in the horizontal plane attracts attention. The height of the buried person (calculated according to the formula of M. Trotter and G. Glaser) is 169.6 cm. The set of features of the considered skull is a brachycrania in combination with a fairly wide, medium-high face, flattened in the horizontal plane, characteristic of archaeological sauromatians and early Sarmatians.&#x0D; The craniological parameters of the considered skull approach the maximum values on the world intergroup scale and are extremely far from the usual set of features characteristic of most ancient series in the territory of the entire Northern Black Sea region. Undoubtedly, the burial is unique, judging by the finds in the grave, which indicates a certain status of a man — a warrior. However, the noted features — brachycrania with weakened horizontal profiling at the upper and middle levels, in combination with the descriptive characteristics of the burial — do not fit into the framework of the known Mediterranean series. This may indicate his origin from a different ethnic environment than the Hellenic one. A similar set of features is characteristic of a number of Sarmatian groups. The material of this well-dated burial complex may be evidence of a rather early penetration of the barbarians into the local Hellenistic circle of the inhabitants of Phanagoria.

Mitochondrial Bioenergy in Neurodegenerative Disease: Huntington and Parkinson.

Strong evidence suggests a correlation between degeneration and mitochondrial deficiency. Typical cases of degeneration can be observed in physiological phenomena (i.e., ageing) as well as in neurological neurodegenerative diseases and cancer. All these pathologies have the dyshomeostasis of mitochondrial bioenergy as a common denominator. Neurodegenerative diseases show bioenergetic imbalances in their pathogenesis or progression. Huntington's chorea and Parkinson's disease are both neurodegenerative diseases, but while Huntington's disease is genetic and progressive with early manifestation and severe penetrance, Parkinson's disease is a pathology with multifactorial aspects. Indeed, there are different types of Parkinson/Parkinsonism. Many forms are early-onset diseases linked to gene mutations, while others could be idiopathic, appear in young adults, or be post-injury senescence conditions. Although Huntington's is defined as a hyperkinetic disorder, Parkinson's is a hypokinetic disorder. However, they both share a lot of similarities, such as neuronal excitability, the loss of striatal function, psychiatric comorbidity, etc. In this review, we will describe the start and development of both diseases in relation to mitochondrial dysfunction. These dysfunctions act on energy metabolism and reduce the vitality of neurons in many different brain areas.

Cerebrospinal fluid concentrations of fluoroquinolones and carbapenems in tuberculosis meningitis.

Background: Tuberculosis meningitis (TBM) is the most lethal form of TB. It is difficult to treat in part due to poor or uncertain drug penetration into the central nervous system (CNS). To help fill this knowledge gap, we evaluated the cerebrospinal fluid (CSF) concentrations of fluoroquinolones and carbapenems in patients being treated for TBM. Methods: Serial serum and CSF samples were collected from hospitalized patients being treated for TBM. CSF was collected from routine lumbar punctures between alternating timepoints of 2 and 6h after drug administration to capture early and late CSF penetration. Rich serum sampling was collected after drug administration on day 28 for non-compartmental analysis. Results: Among 22 patients treated for TBM (8 with confirmed disease), there was high use of fluoroquinolones (levofloxacin, 21; moxifloxacin, 10; ofloxacin, 6) and carbapenems (imipenem, 11; meropenem, 6). Median CSF total concentrations of levofloxacin at 2 and 6h were 1.34mg/L and 3.36mg/L with adjusted CSF/serum ratios of 0.41 and 0.63, respectively. For moxifloxacin, the median CSF total concentrations at 2 and 6h were 0.78mg/L and 1.02mg/L with adjusted CSF/serum ratios of 0.44 and 0.62. Serum and CSF concentrations of moxifloxacin were not affected by rifampin use. Among the 76 CSF samples measured for carbapenem concentrations, 79% were undetectable or below the limit of detection. Conclusion: Fluoroquinolones demonstrated high CSF penetration indicating their potential usefulness for the treatment of TBM. Carbapenems had lower than expected CSF concentrations.

3D Printing in Sustainable Buildings: Systematic Review and Applications in the United Arab Emirates

Three-dimensional printing (3DP) has been rapidly evolving to be one of the leading technology fields in the coming decades. However, as in the early years of new technologies, 3DP suffers from technical limitations and various implications. This study focuses on the applications of 3DP in the construction industry, emphasizing its environmental, financial, and social sustainability aspects. A systematic bibliographic analysis was carried out for the relevant publications which increased by 25-fold from 2014 to 2021. The 3D-printed construction projects in the United Arab Emirates (UAE) are presented to demonstrate the early 3DP technology penetration into its booming construction sector. The UAE case is of particular interest from a sustainability perspective due to the environmental footprint of the ample construction activities in the country, combined with the ambitious strategic plans to achieve sustainable development goals. This critical analysis shows that, despite the limited literature, 3DP could potentially be a sustainable alternative with up to 49% less environmental footprint and 78% more cost-effectiveness compared to conventional construction techniques. As the social sustainability aspect was the least addressed, this study discusses relevant social impact indicators and systematic assessment criteria. It is evident that 3DP is already reshaping the future of the built environment, especially in cases where 3DP is advantageous, such as customized designs, quick project delivery, and sustainability-oriented constructions.

Combined Therapeutic Penetrating Keratoplasty and Pars Plana Vitrectomy for the Treatment of Infectious Keratitis Endophthalmitis: Mexican Endophthalmitis Study Group Protocol 4.

The purpose of this study was to assess the role of combined surgical treatment of therapeutic penetrating keratoplasty and pars plana vitrectomy in the anatomical and functional outcome of infectious keratitis endophthalmitis. This study reviewed the medical records of 4 participating centers in the United States and Mexico. This study included patients with a clinical diagnosis of infectious keratitis endophthalmitis who had been treated with an early therapeutic penetrating keratoplasty and pars plana vitrectomy as the main treatment for endophthalmitis. From each medical record, the study retrieved demographic data, relevant medical and drug history, baseline clinical manifestation of endophthalmitis, best-corrected visual acuity, and the need for enucleation/evisceration for the control of the infection or any other reason through the follow-up. The study included 48 patients (50.15 ± 20.6 years). The mean follow-up time was 13 ± 0.5 months. The mean best-corrected visual acuity at baseline was 2.1 ± 0.25 logarithm of the minimum angle of resolution. At month 12 was 2.09 ± 0.61 logarithm of the minimum angle of resolution ( P = 0.9). The overall prevalence of enucleation/evisceration was 8.3% (95% confidence interval: 2.32%-19.98%). The prevalence of a vision of no-light perception was 20.8% (95% confidence interval: 2.32%-19.98%). Combined surgery for severe cases of infectious keratitis endophthalmitis eradicates the infection in most cases, while significantly improving the overall outcomes.

Insect-parasitic phases in the development of the mycetophagous wood nematode, Bursaphelenchus trypophloei, in its vector, an aspen bark beetle Trypophloeus asperatus

Summary Bursaphelenchus trypophloei is a common wood nematode associated with the poplar bark beetle, Trypophloeus asperatus, in European aspen, Populus tremula. The nematode develops and reproduces in larval galleries of T. asperatus and is transmitted to new breeding trees by adult beetles during their flight and oviposition. Its dispersal third-stage juveniles (DJIII) are unique because of their exceptionally early penetration into the haemocoel of the second- or third-larval stage of the future vector/host and long-term (up to 10 months) occupation of this environment. Detailed morphological/anatomical, and bionomic study revealed that while living in the vector’s haemocoel the nematode dispersal/dauer juveniles pass through a series of intermittent changes with three distinct developmental phases. The sequence of these phases corresponded to the process of diapause observed in many plant and animal parasites. Throughout the period of living in the haemocoel, the nematodes remained at their dispersal juvenile stage (DJIII) but clearly increased in size and changed their morphometrics and shape of such anatomical/morphological characters as the metacorpus and tail terminus. Moreover, the juveniles apparently ingested the food from the vector’s haemolymph. Specifically, in the insect haemocoel, the body of dispersal/parasitic juveniles became less transparent with most organs being obscured by an increasing amount of refractive nutrient storage granules. After penetration into the insect the process of diapause was irreversible, irrespective of the availability of food (i.e., Leptographium spp. fungus). The nematodes could resume their further development only after the natural emergence from the vector beetle to its new galleries or a few days earlier, when mature third phase DJ (DJIII-3) juveniles were dissected from the beetle and transferred to a fresh fungal culture. The data indicate that B. trypophloei is exclusively mycetophagous when free-living in the larval galleries of its insect vector, T. asperatus, and parasitic in the haemocoel of this insect.

Outcomes of Severe Fungal Keratitis Using in vivo Confocal Microscopy and Early Therapeutic Penetrating Keratoplasty.

PurposeThe purpose of this study was to assess the impact of early diagnosis using in vivo confocal microscopy and early therapeutic penetrating keratoplasty (TPK) on the outcomes of severe cases of fungal keratitis.MethodsThis retrospective single-center study included 38 patients (40 eyes) with fungal keratitis who presented between December 2013 and February 2020. Preoperative, intraoperative, and postoperative parameters were recorded to assess the role of early correct diagnosis and early surgical therapy on visual acuity outcome and enucleation rate during follow-up.ResultsThe mean patient age was 51 years (71% females). The initial external diagnosis was correct in 20 cases (50%). The mean time from symptom onset until admission to our department was 46.8 ± 68.0 (median 28.5) days. The mean time to correct diagnosis after admission to our department was 1 day with in vivo confocal microscopy (IVCM). IVCM was performed in 38 cases, of which 36 (sensitivity: 94.7%) were positive for fungal infection. Twenty-seven out of 40 (67.5%) eyes received a TPK 4.2 ± 3.9 days after admission, with a mean graft size of 8.9 ± 1.9 mm. Three eyes (7.5%) were enucleated. The corrected distance visual acuity of the entire study population increased from 2.0 ± 1.2 LogMAR to 0.96 ± 1.17 LogMAR.ConclusionIn vivo confocal microscopy is a powerful tool for the early detection of fungal organisms in infectious keratitis. An early TPK with a large graft helps to eradicate the infection timely and results in a favorable visual acuity outcome and lower enucleation rate, especially when treating filamentous fungi.

Carbon Dioxide Applications for Enhanced Oil Recovery Assisted by Nanoparticles: Recent Developments.

Carbon dioxide (CO2) in enhanced oil recovery (EOR) has received significant attention due to its potential to increase ultimate recovery from mature conventional oil reserves. CO2-enhanced oil recovery (CO2-EOR) helps to reduce global greenhouse gas emissions by sequestering CO2 in subterranean geological formations. CO2-EOR has been exploited commercially over recent decades to improve recovery from light and medium gravity oil reservoirs in their later stages of development. CO2 tends to be used in either continuous flooding or alternated flooding with water injection. Problems can arise in CO2-flooded heterogeneous reservoirs, due to differential mobility of the fluid phases, causing viscous fingering and early CO2 penetration to develop. This study reviews the advantages and disadvantages of the techniques used for injecting CO2 into subsurface reservoirs and the methods adopted in attempts to control CO2 mobility. Recently developed methods are leading to improvements in CO2-EOR results. In particular, the involvement of nanoparticles combined with surfactants can act to stabilize CO2 foam, making it more effective in the reservoir from an EOR perspective. The potential to improve CO2 flooding techniques and the challenges and uncertainties associated with achieving that objective are addressed.