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Nanoparticle (NP) research is an area of scientific interest with high potential for application in biomedical, optical, and electronic fields. Due to their relatively large surface area compared to their mass, NPs can be more chemically reactive and change their reactive strength or other properties. NP-based drug delivery systems provide transport and an effective and controlled way to release the drugs. This work aimed to study the solubility and biological activity of nano-encapsulated copper metal complexes for the induction of toxicity and mortality in larvae of Aedes aegypti mosquitoes. After the nano-encapsulated metal complexes were prepared, the efficiency of this incorporation was determined by electron paramagnetic resonance, and toxicity bioassays were performed. The polymeric-based PLGA NPs encapsulating metal complexes exhibited high toxicity and specificity for target organisms (insect vectors, i.e., A. aegypti ), with relatively less environmental impact and long-term control of their breeding., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

The second most common form of Charcot-Marie-Tooth disease (CMT) follows an X-linked dominant inheritance pattern (CMTX1), referring to mutations in the gap junction protein beta 1 gene ( GJB1 ) that affect connexin 32 protein (Cx32) and its ability to form gap junctions in the myelin sheath of peripheral nerves. Despite the advances of next-generation sequencing (NGS), attention has only recently also focused on noncoding regions. We describe two unrelated families with a c.-17+1G>T transversion in the 5' untranslated region (UTR) of GJB1 that cosegregates with typical features of CMTX1. As suggested by in silico analysis, the mutation affects the regulatory sequence that controls the proper splicing of the intron in the corresponding mRNA. The retention of the intron is also associated with reduced levels of the transcript and the loss of immunofluorescent staining for Cx32 in the nerve biopsy, thus supporting the hypothesis of mRNA instability as a pathogenic mechanism in these families. Therefore, our report corroborates the role of 5' UTR of GJB1 in the pathogenesis of CMTX1 and emphasizes the need to include this region in routine GJB1 screening, as well as in NGS panels.

Aedes aegypti is the main mosquito vector of dengue, zika, chikungunya, and yellow fever diseases. The low effectiveness of vector control options is mainly related to the increased insect's resistance and to the toxicity of products used for non-target organisms. The development of new environmentally friendly and safer products is imperative. Technical cashew nut shell liquid (tCNSL), mostly composed by cardanol (C), is an abundant by-product of the cashew (Anacardium occidentale L.) production chain, available at low cost, and with proven larvicidal activity. However, chemical modifications in both tCNSL and cardanol were required to increase their water solubilities. Our objectives were to synthesise and characterise sustainable, low-cost and easy-to-use multiple function products based on tCNSL, cardanol, and the sulphonates obtained from both; and to evaluate all these products efficacy as surfactants, larvicidal, and antimicrobial agents. None of the sulphonates presented antimicrobial and larvicidal activities. tCNSL and cardanol were successfully emulsified with sodium technical cashew nut shell liquid sulphonate (NatCNSLS, complex mixture of surfactants). The emulsions obtained presented larvicidal activity due to the presence of tCNSL and cardanol in their composition. Our results showed that the tCNSL+NatCNSLS mixture emulsion was an effective larvicide and surfactant multiple function product, with high availability and easy-to-use, which can facilitate its large-scale use in different environments. Graphical abstract.

Aedes aegypti ( Ae. aegypti ) is a competent vector for transmitting important viral diseases such as yellow fever, dengue, chikungunya, and Zika. Several strategies have been applied to avoid Ae. aegypti proliferation by using environmental management, biological, and chemical approaches. However, the development of new methods for effective control of the insect vector population is still needed. Photodynamic control is an alternative way to control the vector population by using a physical approach based on the larval phototoxicity of a photosensitizer. In this context, the present study evaluated the use of eosin-methylene blue (EMB) as a new photosensitizer for photodynamic control of Ae. aegypti larval populations. The photodynamic assays were performed submitting Ae. aegypti third-instar larvae to different EMB concentrations (0.0, 0.5, 1.0, 5.0, 10.0, 50.0, and 100.0 µg mL -1 ) in combination of three different light doses (24.3, 48.6, and 97.2 J cm -2 ) under either white-light radiation from RGB LEDs or sunlight. The results demonstrated that EMB presented a rapid internalization into the larvae and was phototoxic. The photodynamic action induced 100% of larval mortality after about 40 min of sunlight irradiation even using low EMB concentration (0.5 µg mL -1 ). The findings reveal EMB as an effective photoactive compound to control larval populations of Ae. aegypti by photodynamic process induced by either sunlight or white-light from RGB LEDs.

Objective: Nerve ultrasound (US) data on myelin protein zero (MPZ)-related Charcot-Marie-Tooth disease (CMT) are lacking. To offer a comprehensive perspective on MPZ-related CMTs, we combined nerve US with clinics, electrodiagnosis and histopathology., Methods: We recruited 36 patients (12 MPZ mutations), and correlated nerve US to clinical, electrodiagnostic measures, and sural nerve biopsy., Results: According to motor nerve conduction velocity (MNCV) criteria, nine patients were categorized as "demyelinating" CMT1B, 17 as "axonal" CMT2I/J, and 10 as dominant "intermediate" CMTDID. Sural nerve biopsy showed hypertrophic de-remyelinating neuropathy with numerous complex onion bulbs in one patient, de-remyelinating neuropathy with scanty/absent onion bulbs in three, axonal neuropathy in two, mixed demyelinating-axonal neuropathy in five. Electrodiagnosis significantly differed in CMT1B vs. CMT2I/J and CMTDID subgroups. CMT1B had slightly enlarged nerve cross sectional area (CSA) especially at proximal upper-limb (UL) sites. CSA was negatively correlated to UL MNCV and not increased at entrapment sites. Major sural nerve pathological patterns were uncorrelated to UL nerve US and MNCV., Conclusions: Sural nerve biopsy confirmed the wide pathological spectrum of MPZ-CMT. UL nerve US identified two major patterns corresponding to the CMT1B and CMT2I/J-CMTDID subgroups., Significance: Nerve US phenotype of MPZ-CMT diverged from those in other demyelinating peripheral neuropathies and may have diagnostic value., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Cardanol is a constituent of Cashew Nut Shell Liquid that presents larvicidal activity against Aedes aegypti. The isolation of cardanol is somewhat troublesome, however, in this work we describe an efficient and inexpensive method to obtain it as a pure material. The compound was used as starting material to make chemical transformation leading to saturated cardanol, epoxides and, halohydrins. These derivatives were tested for toxicity against Aedes aegypti larvae. The results showed that iodohydrins are very promising compounds for making commercial products to combat the vector mosquito larvae presenting a LC50 of 0.0023 ppm after 72 h of exposure.

Control strategies using insecticides are sometimes ineffective due to the resistance of the insect vectors.In this scenario new products must be proposed for the control of insect vectors.The complexes L-aspartate Cu (II) and L-glutamate-Cu (II) complexes were synthesized and characterized by elemental analysis, visible ultraviolet, infrared spectroscopy and potentiometric titration. The toxicity of these complexes was analyzed in Aedes aegypti (Diptera: Culicidae) larvae and Gram-negative and Gram-positive bacteria. The interaction between the ligands and the amino acid balance and the distribution of the species as a function of pH were discussed. The lethal concentration median (LC50) for Ae. aegypti larvae were: L-glutamic acid-Cu (II) - 53.401 mg L-1 and L-aspartate-Cu (II) - 108.647 mg L-1. The minimum inhibitory concentration (MIC) required for Staphylococcus aureus and Escherichia coli was: L-glutamate-Cu (II) 500-2000 mg L-1 and L-aspartate-Cu (II) 1000-2000 mg L-1. The concentrations demonstrated toxicity that evidence the potential of the complexes as bactericide and insecticide. Metal complexes formed by amino acids and transition metals are advantageous because of low environmental toxicity, biodegradability and low production cost.

IgM paraproteins often present reactivity to myelin-associated glycoprotein (MAG) and sulfatide. We describe the clinical and neurophysiological findings, and therapy response in 21 patients with IgM paraproteinemic neuropathy (15 with anti-MAG antibodies, 1 with anti-sulfatide antibodies, and 5 with both reactivity), and in 2 with anti-sulfatide positivity and no hematological disease. All patients complained of sensory symptoms, the majority had demyelinating neuropathy. Indirect immunofluorescence on human normal sural nerves disclosed different staining patterns. Eight of 13 patients (6 anti-MAG, 1 anti-sulfatide, 1 both anti-sulfatide and anti-MAG antibodies) improved after Rituximab. IVIg, steroids and plasma-exchange were also administered with different responses., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Circulating Pentraxin 3 (PTX3) and vascular endothelial growth factor (VEGF) levels were measured longitudinally (mean follow-up 2 years) by ELISA in 6 patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome and 16 controls. Expression of PTX3 was also assessed (immunohistochemistry) on sural nerve biopsies from POEMS and vasculitic neuropathy patients. No correlation was found between PTX3 and VEGF levels in POEMS or controls. Sural nerve biopsies from vasculitic neuropathy patients, but not those from POEMS syndrome, showed strong PTX3 staining. PTX3, expression of vessel inflammation/remodeling, and VEGF, crucial pro-angiogenic cytokine, appear to be independently regulated in POEMS syndrome., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Genetic germinal and somatic mosaicisms of dominant Charcot-Marie-Tooth disease (CMT) mutations are rarely reported and/or recognized. We describe a novel heterozygous p.Trp39Cys missense mutation in the extracellular domain of the peripheral myelin protein 22 (PMP22) associated with an early-onset demyelinating CMT type 1 E (CMT1E) in two siblings born from asymptomatic non-consanguineous parents. The 29-year-old mother, harboring approximately 20% of the mutant PMP22 allele in blood, had minor signs of distal polyneuropathy (pes cavus, decreased ankle jerk reflexes and vibration sense in legs) and slight reduction of sural nerve action potentials (SNAPs). Authors suggest that mutations of CMT-related genes which originate in post-zygotic stages may be associated with mild phenotypes of peripheral neuropathy., (© 2012 Peripheral Nerve Society.)

Autosomal-dominant transthyretin (TTR)-related amyloidosis usually manifests in the second to fourth decade with a length-dependent axonal neuropathy with prominent involvement of the small fibers and multi-organ systemic failure. We retrospectively analyzed seventeen probands, including thirteen apparently isolated cases, carrying eight mutations of TTR gene (age of onset = 60.4 ± 13.5 years). Thirteen patients were initially un/misdiagnosed; interval from onset to definite diagnosis was 3.3 ± 2.3 years. Inaugural syndromes were a length-dependent motor-sensory neuropathy in seven cases, a sensory neuropathy in four, an isolated carpal tunnel syndrome in three, a pure dysautonomia in two, and a painful neuropathy in one. Atypical presentations included demyelinating nerve conduction changes with increased cerebrospinal fluid proteins resembling chronic inflammatory demyelinating polyradiculoneuropathy and a predominantly motor involvement resembling a motor neuron disorder. Misleading findings also included amyloid-negative abdominal fat aspirate/biopsy, biclonal gammopathy, and hepatitis C virus (HCV) seropositivity. Sural nerve biopsy detected amyloid deposits in thirteen of fifteen patients, including one case with a previous negative biopsy. TTR-immunohistochemistry was necessary to complete the diagnosis of primary amyloidosis light chain in a patient with biclonal gammopathy. A recurrent p.Phe64Leu mutation manifested in the seventh decade with painful motor-sensory polyneuropathy, dysautonomia, bulbar palsies, and fasciculations. TTR should be tested in a wide clinical spectrum of cryptogenetic, progressive, and motor-sensory neuropathies even manifesting with a very late onset., (© 2011 Peripheral Nerve Society.)

Charcot-Marie-Tooth disease type 1B (CMT1B) and Déjerine-Sottas syndrome type B (DSSB) are caused by missense or frameshift mutations of myelin protein zero (MPZ) gene. We identified an apparently silent synonymous c.411C>T transition in MPZ exon 3 (p.Gly137Gly) which segregated with DSS in a two-generation pedigree. Retro-transcriptional analysis of MPZ in the proband's archive sural nerve biopsy identified an r.410_448del mutant transcript which resulted from an activated cryptic splice site in exon 3 and led to an in-frame partial deletion of exon 3 (p.Gly137_Lys149del). Quantitative real-time polymerase chain reaction (QRT-PCR) compared with two unrelated CMT1B nerves carrying a frameshift c.306delA mutation (p.Asp104ThrfsX13) indicated that the r.410_448del was stable differing from the p.Asp104ThrfsX13-associated transcript which was subjected to nonsense-mediated decay. The report highlighted the possible pathogenic role of synonymous MPZ mutations and difficulties in interpreting results from routine mutational screenings., (© 2011 Peripheral Nerve Society.)

The peripheral myelin protein 22 gene (PMP22) encodes an intrinsic membrane protein of compact myelin. Duplication or deletion of PMP22 causes the most common autosomal dominant neuropathies, Charcot-Marie-Tooth disease type 1A or hereditary neuropathy with liability to pressure palsies. Charcot-Marie-Tooth disease type 1A is a hypertrophic de-remyelinating neuropathy manifesting with peroneal muscular atrophy and uniform, marked, slowing of nerve conduction velocities. Hereditary neuropathy with liability to pressure palsies is a recurrent focal neuropathy with sausage-like myelin thickening (tomacula) and non-uniform nerve conduction velocity changes. Missense or nonsense mutations also cause more severe Charcot-Marie-Tooth disease type 1A forms of infancy or hereditary neuropathy with liability to pressure palsies, but they are presumably very rare. We performed a mutational scanning of PMP22 in 229 index patients (46 familial, 183 isolated) referred for suspected inherited neuropathy. The series included 125 cases with hereditary neuropathy with liability to pressure palsies (mean age 42.5 years), 47 cases with Charcot-Marie-Tooth disease type 1A (motor nerve conduction velocities at median nerve below 38 m/s) (mean age 40.7 years) and 57 cases with Charcot-Marie-Tooth with unknown nerve conduction velocities (mean age 43 years). Preliminary molecular studies ruled out PMP22 duplication or deletion or mutations in a comprehensive panel of Charcot-Marie-Tooth genes. Mutational scanning of PMP22 was done by denaturing high performance liquid chromatography and automated nucleotide sequencing. To investigate the molecular basis of phenotype-to-genotype correlations, we performed a transcriptional analysis of PMP22 using reverse-transcriptase polymerase chain reaction and quantitative real-time polymerase chain reaction in two phenotypically divergent nerve biopsies. Ten patients harboured eight micromutations of PMP22 including four novel changes. In six familial and three sporadic cases, detected mutations caused premature or delayed stop codons and were associated with hereditary neuropathy with liability to pressure palsies; the related pathological pictures ranged from classical tomaculous neuropathy to a mild demyelinating neuropathy with atypical non-tomaculous myelin thickenings. In a single family a c.179-2A> G mutation affecting the splice acceptor site of intron 2 cosegregated with a Charcot-Marie-Tooth disease type 1A-like syndrome and a peculiar pathological picture of demyelinating neuropathy without Charcot-Marie-Tooth disease type 1A-like classical onion bulbs or tomacula. Transcriptional analysis of a novel c.174_178 + 7delAAACGGTGAGGC deletion involving exon 2 and intron 2 demonstrated an unstable mutant transcript leading to a p.Asn59GlyfsX12 change; the mutation represented a null allele and caused a typical tomaculous hereditary neuropathy with liability to pressure palsies. The Charcot-Marie-Tooth disease type 1-like c.179-2A > G allele led to a stable transcript with an in-frame deletion of exon 3 (p.Glu60_Ala106del); the predicted shorter protein could exert variable molecular effects. In conclusion, micromutations of PMP22 cause a clinical and pathological continuum of demyelinating neuropathies that may include atypical phenotypes.

Studies have demonstrated that electronic mosquito repellers are useless and that some of them could even increase the attraction of mosquitoes. While testing some electronic repellers, we noted that they also promoted an increase in biting rates. The present work has evaluated three commercial devices and a computer program working on five different sound frequencies. In a test chamber, the number of Aedes aegypti L. bite attempts was computed during four cycles of 3 min each by alternately turning the devices off and on. The mosquito biting rates for five sound frequencies (ranging from 9.6 kHz to 18.2 kHz) initially demonstrated a significant increase (ranging from around 20% to 50%), which decreased from 8.3% to 25.1% when the repellers were turned off. The biting rate significantly increased at 11.8 kHz (33.7%) when the device was turned on again. The danger of using electronic repellers and the role of sound frequencies stimulating mosquito biting are discussed.

ABSTRACT. The abilities of Aedes aegypti and Ae. albopictus females in trespassing 5 different commercial nets, 2 nets impregnated with deltamethrin or permethrin and 3 non-impregnated nets (Guarany, Perame, and Ricca), were compared. The evaluating parameters were their percent trespassing success, the median trespassing time (TT50), and the relation between mosquito wing sizes and their trespassing success. Some mosquito behavioral traits were also observed. The trespassing success, directly related to opening areas, was found to be lower with impregnated nets for both species. The differences between the mosquito species were significant among all the nets except Ricca. Aedes albopictus showed a very high success rate in trespassing the non-impregnated Perame net and a lower success rate in trespassing Guarany. Aedes albopictus also showed a very high success rate in trespassing pyrethroid-impregnated nets. The TT50 values for the Ricca and Guarany nets were not significantly different between the species, but a significantly lower TT50 value was found for the net with the largest opening (Ricca). The smaller wingspan of Ae. albopictus seems to explain the higher trespassing success of this species.

Autosomal dominant Charcot-Marie-Tooth disease type 1B (CMT1B) is caused by heterozygous mutations in the extracellular domain of P0. Here, we investigated clinically, electrophysiologically and pathologically a pedigree with a novel mutation in the intracellular domain of P0 (P0ic). The mutational analysis included denaturing high performance liquid chromatography (DHPLC) and nucleotide sequencing. Two patients from subsequent generations were homozygous for an Asp195Tyr mutation in the intracellular domain of P0 (P0ic), whereas two healthy individuals with minimal electrophysiological changes were heterozygous for the same mutation. The authors conclude that mutations of P0ic may undergo a gene dosage effect manifesting semidominant inheritance.