Search

The state-of-the-art, simple and scalable methods for lignin micro-/nano-particles recovery from agricultural biomasses were evaluated in this review. Being non-wood biomasses, these materials can be easily fibrillated, supporting the usage of mild soda or organic solvent pretreatment. Different approaches in particle recovery were compared to conclude that the bottom-up approach facilitates smaller particles towards the nano-size range whereas mechanical treatment can act as a supporting method to increase uniformity and reduce particle sizes after bottom-up precipitation. By combining with the pretreatment steps, direct one-pot lignin micro-/nano-particle recovery can be achieved using the lignin-containing black liquor or organosolv liquor. These lignin micro-/nano-particles can then be applied as high-value functional products in cosmetics, pharmaceuticals, environmental remediation, and energy sectors. The systematic evaluation of lignin micro-/nano-particles recovery from agricultural biomasses in this review can support the full utilization of these natural resources to aim towards a circular agriculture., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Open wounds present a significant challenge in healthcare, requiring careful management to prevent infection and promote wound healing. Advanced wound dressings are critical need to enhance their hemostatic capabilities, antimicrobial properties, and ability to support angiogenesis and sustained moisture for optimal healing. This study introduces a flexible hemostatic dressing designed for open wounds, integrating chitosan (CS) for hemostasis and biocompatibility, silk fibroin (SF) for mechanical strength, and montmorillonite (MMT) for enhanced drug transport. The CSSF@MMT dressings showed promising mechanical strength and swift hemostasis. The CIP-loaded CSSF@MMT demonstrated sustained release for up to one week, exhibiting antibacterial properties against both Gram-positive and Gram-negative bacteria. In vitro cell migration assay demonstrated that erythropoietin-loaded CSSF@MMT dressings promoted the proliferation and migration of endothelial cells. Similarly, the chick embryo chorioallantoic membrane study indicated the same dressings exhibited a significant increase in vascular regeneration. This research suggests that the CSSF@MMT sponge dressing, incorporated with CIP and erythropoietin, holds promise in effectively halting bleeding, creating a protective environment, diminishing inflammation, and fostering wound tissue regeneration. This potential makes it a significant advancement in open wound care, potentially lowering the need for limb amputation and decreasing wound care burden worldwide., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

For the first time, ultrasonic emulsification was studied for cinnamon essential oil (CEO) Pickering emulsion, stabilized by cellulose nanocrystal (CNC) from rice straw. Sonication proved to be an effective method for emulsifying CEO, creating small emulsion droplets around 700 nm in size, with an even dispersion characterized through a low polydispersity index. The biomass-derived CNC exhibits high encapsulation efficiency (> 95 %) with varying CEO concentration (5-25 vol%), creating droplets with negative surface charge with limited aggregation of emulsions. Optimization through the Box Behnken design using response surface methodology provides a model for the interaction and effects of variables towards the formulation. Optimal condition was concluded to be at 11.47 vol% CEO, 0.84 wt/vol% CNC and at 6 sonication cycles. The optimized Pickering emulsions retain the antimicrobial properties of CEO, with a large inhibition zone and low MIC value of around 0.048 vol% CEO. DPPH inhibition assay indicates that the emulsification process enhances the antioxidation properties of cinnamon essential oil, expressed through a lower IC 50 of 0.90 vol% CEO, in comparison to pure essential oil at 1.33 vol% CEO. Overall, this research proposes a novel approach towards using nanocellulose as carriers for essential oil with potential in a large variety of applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The standing pouch, a packaging material made of multiple layers of plastic and metal, presents a significant challenge for full recycling. Gasification shows promise as a method to recover aluminum from this type of waste and convert it into energy. This study aims to evaluate the efficiency of gasification in treating aluminum-containing plastic packages, and recovering aluminum while identifying the optimal combinations of temperature and equivalence ratio (ER) to achieve the best outcomes. The study achieved a conversion rate of 43.06 wt% to 69.42 wt% of the original waste mass into syngas, with aluminum recovery rates ranging from 35.2 % to 65.3 %. Temperature and ER alterations affected the product distribution, aluminum recovery rate, and aluminum partitioning in the products. The results indicated that the combination of 700 °C, ER = 0.4 would provide the largest amount of syngas about 69.42 %, which is the main product of the gasification process, and therefore, this combination is the most optimal for syngas-yielding purposes. Under the reclaiming aluminum is more prioritized, the combination of 800 °C, ER = 0.6 would be the most optimal condition, the majority of Al in fuel was found in char and fly ash were 67.5 % and 4.81 %, respectively. The study focused on the partitioning of aluminum during the gasification process, which was observed to mainly exist in the form of Al 2 O 3 (s), with gaseous species including AlCl 3 (g), AlH(g), and Al 2 O(g) due to their medium volatility. As the ER increased, the amount of O 2 also increased, leading to more Al 2 O 3 (s) formation. In conclusion, this research provides a foundation for further exploration of gasification as a means of energy conversion and metal recovery., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Thi Ngoc Lan Thao Ngo reports financial support was provided by Vietnam National University Ho Chi Minh City. Thi Ngoc Lan Thao Ngo reports a relationship with Vietnam National University Ho Chi Minh City that includes: employment. 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]., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Machine learning (ML) techniques have shown great potential for screening corrosion inhibitors. In this study, a data-driven quantitative structure-property relationship (QSPR) model using the gradient boosting decision tree (GB) algorithm combined with the permutation feature importance (PFI) technique was developed to predict the corrosion inhibition efficiency (IE) of organic compounds on carbon steel. The results showed that the PFI method effectively selected the molecular descriptors most relevant to the IE. Using these important molecular descriptors, an IE predictive model was trained on a dataset encompassing various categories of organic corrosion inhibitors for carbon steel, achieving RMSE, MAE, and R 2 of 6.40%, 4.80%, and 0.72, respectively. The integration of GB with PFI within the ML workflow demonstrated significantly enhanced IE predictive capability compared to previously reported ML models. Subsequent assessments involved the application of the trained model to drug-based corrosion inhibitors. The model demonstrates robust predictive capability when validated on available and our own experimental results. Furthermore, the model has been employed to predict IE for more than 1500 drug compounds, suggesting five novel drug compounds with the highest predicted IE on carbon steel. The developed ML workflow and associated model will be useful in accelerating the development of next-generation corrosion inhibitors for carbon steel., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Recent studies have developed varied delivery systems incorporating natural compounds to improve the limitations of plant extracts for clinical use while enabling their controlled release at treatment sites. For the first time, ethanolic limeberry extract (Triphasia trifolia) has been successfully encapsulated in thermo-sensitive chitosan hydrogels by a facile in situ loading. The extract-incorporated chitosan hydrogels have a pH value of nearly 7.00, gelation temperatures in the range of 37-38 °C, and exhibit an open-cell porous structure, thus allowing them to absorb and retain 756 % of their mass in water. The in vitro extract release from the hydrogels is driven by both temperature and pH, resulting in more than 70 % of the initial extract being released within the first 24 h. Although the release half-life of hydrogels at pH 7.4 is longer, their release capacity is higher than that at pH 6.5. Upon a 2 °C increase in temperature, the time to release 50 % initial extract is sharply reduced by 20-40 %. The release kinetics from the hydrogels mathematically demonstrated that diffusion is a prominent driving force over chitosan relaxation. Consequently, the developed hydrogels encapsulating the limeberry extract show their heat and pH sensitivity in controlled release for treating chronic wounds., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The global trend of increasing energy demand along the large volume of wastewater generated annually from the paper pulping and cellulose production industries are considered as serious dilemma that may need to be solved within these current decades. Within this discipline, lignin, silica or lignin-silica hybrids attained from biomass material have been considered as prospective candidates for the synthesis of advanced materials. In this study, the roles and linking mechanism between lignin and silica in plants were studied and evaluated. The effects of the extraction method on the quality of the obtained material were summarized to show that depending on the biomass feedstocks, different retrieval processes should be considered. The combination of alkaline treatment and acidic pH adjustment is proposed as an effective method to recover lignin-silica with high applicability for various types of raw materials. From considerations of the advanced applications of lignin and silica materials in environmental remediation, electronic devices and rubber fillers future valorizations hold potential in conductive materials and electrochemistry. Along with further studies, this research could not only contribute to the development of zero-waste manufacturing processes but also propose a solution for the fully exploiting of by-products from agricultural production., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this research, a novel composite material composed of Metal-Organic Framework material (MOF) and graphite oxide was synthesized and evaluated as a possible drug-loading vehicle. HKUST-1, a MOF material originally designed by the Hong Kong University of Science and Technology, was used as a model porous material. The aim was to synthesize a drug delivery vehicle for modifying the release kinetics and solubility of poorly soluble drugs (BSC Class II drugs); these are drugs that are known to have poor bioavailability due to their low solubility. We used ketoprofen, ibuprofen, and felodipine as models for BSC Class II drugs. The drugs were loaded onto composite materials through adsorption. The adsorption of these three drugs into the matrix of HKUST-1/GO (graphite oxide), HKUST-1, and graphite oxide was compared. The loading efficiency of the drugs onto the carrier was dependent on the drug molecule and the composition of the drug carrier. The inclusion of graphite oxide in the drug carrier matrix improved the drug loading capacity and modified the drug release rate. The loading of the three drugs felodipine, ketoprofen, and ibuprofen onto HKUST-1 were 33.7, 58, and 79 mg/g respectively. The incorporation of GO into the HKUST-1 matrix resulted in an increase in the loading by 16 and 4 mg/g for the ketoprofen and ibuprofen drugs. When compared to the pure drugs, the solubility of all three drugs in the HKUST-1/GO matrix increased by at least 6 folds.

Six previously undescribed components, bis(4-glycosyloxybenzyl) 2-isobutyltartrate derivatives (pholidotoside A-E) and phenolic glycoside (pholidotosin A), together with twenty known compounds were isolated from the pseudobulbs of Pholidota chinensis. Their structures and absolute configuration were elucidated and established through various spectroscopic and chemical methods. The anti-inflammatory potential of selected compounds was examined using a human neutrophil cell model activated by N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB). Among these, dihydrophenanthrenes exhibited potent inhibitory effect on both superoxide anion generation and elastase release assays with IC 50 values ranging from 0.41 ± 0.05 to 7.14 ± 0.30 μM., Competing Interests: Declaration of competing interest 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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Chitosan hydrogel is a smart and highly applicable drug delivery carrier because of its nature, biocompatibility, biodegradability, and ability to encapsulate, carry and release the drug to the desired target flexibly depending on the conditions of the patient. Not only developing delivery systems but natural compounds are also increasingly being studied in supporting the treatment of diseases. However, the physicochemical and pharmacokinetic issues of the phytochemicals are remaining. This review summarizes the remarkable properties of chitosan hydrogel; approaches to loading natural extracts on the hydrogels to overcome the susceptibility of the phytochemicals to degradation; and their applications in biomedical fields. The drug loading efficiency, release profile, in vitro and in vivo results of the chitosan hydrogels carrying natural compounds are discussed to point out the remaining challenges of combining the extracts with chitosan hydrogels and controlling the release of the carried substances., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Depolymerization of lignin is an important step to obtain a lignin monomer for the synthesis of functional chemicals. In the context of more lignin produced from biomass and pulp industry, converting real lignin with low purity is still required more studies. In this study, the influence of solvent composition and reaction parameters such as binary solvents ratio, time, and temperature, the solvent-to-lignin ratio on the depolymerization of rice straw lignin was investigated carefully. Essential lignin-degraded products including liquid product (LP), char (solid), and gas were obtained, and their yields were directly influenced by reaction conditions. Results show that the maximum lignin conversion rate of 92% and LP yield of 66% was under the condition of 275°C, 30 min, 75 : 1 (mL solvent/1 g lignin), and ethanol 50%. Gas chromatography-mass spectroscopy (GC-MS) analysis was used for the analysis of the depolymerization products and identified 11 compounds which are mainly phenolic compounds such as 2-ethylphenol, 3-ethylphenol, phenol, methyl 2,4,6-trimethylbenzoate. The structure changes of LP and char in various conditions were analyzed using Fourier-transform infrared (FTIR)., Competing Interests: The authors declare that there are no conflicts of interest requiring disclosure in this article., (Copyright © 2022 Viet T Tran et al.)

Improvement of biomass utilization productivity following cascading strategy is a priority for the biorefinery-based circular bioeconomy. In recent years, the field of energy research has seen an increasing interest in bio-products from paddy-based biorefinery, but the utilization of the entire value of paddy biomass to guide the commercial viability of its products has not been got feasible outcomes. Here we propose a potential pathway for a conceptual paddy biorefinery framework by addressing wastes for producing more products. The feasibility of the integrated biorefinery was demonstrated by the conversion of wastes into value-added products such as nano-silica and lignin. In particular, this is the first time that silica recovered from bioethanol system was continued to be reused to produce ZSM-5 and Ni/ZSM-5 as catalysts of rice straw lignin depolymerization achieving high conversion of lignin up to 95% and fair yield of phenolic products up to 41%. Material flow of an integrated biorefinery model was reported to give a future outlook for making most of the processing routes of rice residues. We also established a life cycle that follows the circular bioeconomy concept and discussed the relationship between each of potential bioproducts and their market opportunities., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Tons of waste from residential, commercial and manufacturing activities are generated due to the growing population, urbanization and economic development, prompting the need for sustainable measures. Numerous ways of converting waste to aerogels, a novel class of ultra-light and ultra-porous materials, have been researched to tackle the issues of waste. This review provides an overview of the status of aerogels made from agricultural waste, municipal solid, and industrial waste focusing on the fabrication, properties, and applications of such aerogels. The review first introduced common methods to synthesize the aerogels from waste, including dispersion and drying techniques. Following that, numerous works related to aerogels from waste are summarized and compared, mainly focusing on the sustainability aspect of the processes involved and their contributions for environmental applications such as thermal insulation and oil absorption. Next, advantages, and disadvantages of the current approaches are analyzed. Finally, some prospective waste aerogels and its applications are proposed., Competing Interests: Conflict of interestThere are no conflicts to declare., (© The Author(s), under exclusive licence to Springer Nature B.V. 2021.)

Difficulties in the production of lignin from rice straw because of high silica content in the recovered lignin reduce its recovery yield and applications as bio-fuel and aromatic chemicals. Therefore, the objective of this study is to develop a novel method to reduce the silica content in lignin from rice straw more effectively and selectively. The method is established by monitoring the precipitation behavior as well as the chemical structure of precipitate by single-stage acidification at different pH values of black liquor collected from the alkaline treatment of rice straw. The result illustrates the significant influence of pH on the physical and chemical properties of the precipitate and the supernatant. The simple two-step acidification of the black liquor at pilot-scale by sulfuric acid 20w/v% is applied to recover lignin at pH 9 and pH 3 and gives a percentage of silica removal as high as 94.38%. Following the developed process, the high-quality lignin could be produced from abundant rice straw at the industrial-scale.

A promising and economic material for various applications, such as thermal insulation in construction building and oil clean-up in marine ecosystems, is successfully developed from the by-product of the sugarcane industry. Biodegradable sugarcane bagasse aerogels are produced using polyvinyl alcohol (PVA) binder, followed by a freeze-drying method. This environmental-friendly recycled aerogel has an ultra-low density ([0.016-0.112] g/cm 3 ), a high porosity ([91.9-98.9]%), and a very low thermal conductivity ([0.031-0.042] W/mK). Its superhydrophobicity properties and its maximum oil absorption capacity (up to 25 g/g) are measured after coating aerogel samples with methyltrimethoxysilane (MTMS). The biodegradable aerogel has a Young's modulus of 88 K Pa and can be bent without breaking, demonstrating its high flexibility., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Over the last 15 years, hand, foot, and mouth disease (HFMD) has emerged as a major public health burden across the Asia-Pacific region. A small proportion of HFMD patients, typically those infected with enterovirus 71 (EV71), develop brainstem encephalitis with autonomic nervous system (ANS) dysregulation and may progress rapidly to cardiopulmonary failure and death. Although milrinone has been reported to control hypertension and support myocardial function in two small studies, in practice, a number of children still deteriorate despite this treatment. Magnesium sulfate (MgSO4) is a cheap, safe, and readily available medication that is effective in managing tetanus-associated ANS dysregulation and has shown promise when used empirically in EV71-confirmed severe HFMD cases., Methods/design: We describe the protocol for a randomized, placebo-controlled, double-blind trial of intravenous MgSO4 in Vietnamese children diagnosed clinically with HFMD plus ANS dysregulation with systemic hypertension. A loading dose of MgSO4 or identical placebo is given over 20 min followed by a maintenance infusion for 72 h according to response, aiming for Mg levels two to three times the normal level in the treatment arm. The primary endpoint is a composite of disease progression within 72 h defined as follows: development of pre-specified blood pressure criteria necessitating the addition of milrinone, the need for ventilation, shock, or death. Secondary endpoints comprise these parameters singly, plus other clinical endpoints including the following: requirement for other inotropic agents; duration of hospitalization; presence of neurological sequelae at discharge in survivors; and neurodevelopmental status assessed 6 months after discharge. The number and severity of adverse events observed in the two treatment arms will also be compared. Based on preliminary data from a case series, and allowing for some losses, 190 patients (95 in each arm) will allow detection of a 50 % reduction in disease progression with 90 % power at a two-sided 5 % significance level., Discussion: Given the large numbers of HFMD cases currently being seen in hospitals in Asia, if MgSO4 is shown to be effective in controlling ANS dysregulation and preventing severe HFMD complications, this finding would be important to pediatric care throughout the region., Trial Registration: ClinicalTrials.gov Identifier: NCT01940250 (Registered 22 August 2013).

Enterovirus 71 (EV71) frequently causes fatal infections in young children in Asia. In 2011, EV71 epidemics occurred in southern Vietnam. We conducted genetic and antigenic analysis of the EV71 isolates and found that 94% of them were genotype C4a related to two lineages circulating in China and 6% were genotype C5 which have circulated in Vietnam since 2003. Antigenic variants were not detected. EV71 vaccines are being developed. Longitudinal enterovirus surveillance data are critical to formulate vaccination policy in Vietnam.

Objective: Enterovirus 71-induced brainstem encephalitis with pulmonary edema and/or neurogenic shock (stage 3B) is associated with rapid mortality in children. In a small pilot study, we found that milrinone reduced early mortality compared with historical controls. This prospective, randomized control trial was designed to provide more definitive evidence of the ability of milrinone to reduce the 1-week mortality of stage 3B enterovirus 71 infections., Design: Prospective, unicenter, open-label, randomized, controlled study., Setting: Inpatient ward of a large tertiary teaching hospital in Ho Chi Minh City, Vietnam., Patients: Children (≤ 18 yr old) admitted with proven enterovirus 71-induced pulmonary edema and/or neurogenic shock., Interventions: Patients were randomly assigned to receive intravenous milrinone (0.5 μg/kg/min) (n = 22) or conventional management (n = 19). Both groups received dopamine or dobutamine and intravenous immunoglobulin., Measurements and Main Results: The primary endpoint was 1-week mortality. The secondary endpoints included length of ventilator dependence and hospital stay and adverse events. The median age was 2 years with a predominance of boys in both groups. The 1-week mortality was significantly lower, 18.2% (4/22) in the milrinone compared with 57.9% (11/19) in the conventional management group (relative risk = 0.314 [95% CI, 0.12-0.83], p = 0.01). The median duration of ventilator-free days was longer in the milrinone treatment group (p = 0.01). There was no apparent neurologic sequela in the survivors in either group, and no drug-related adverse events were documented., Conclusions: Milrinone significantly reduced the 1-week mortality of enterovirus 71-induced pulmonary edema and/or neurogenic shock without adverse effects. Further studies are needed to determine whether milrinone might be useful to prevent progression of earlier stages of brainstem encephalitis.

We prospectively studied 3,791 children hospitalized during 2011 during a large outbreak of enterovirus 71-associated hand, foot, and mouth disease in Vietnam. Formal assessment of public health interventions, use of intravenous immunoglobulin and other therapies, and factors predisposing for progression of disease is needed to improve clinical management.

Optic Atrophy 1 (OPA1) is a ubiquitously expressed dynamin-like GTPase in the inner mitochondrial membrane. It plays important roles in mitochondrial fusion, apoptosis, reactive oxygen species (ROS) and ATP production. Mutations of OPA1 result in autosomal dominant optic atrophy (DOA). The molecular mechanisms by which link OPA1 mutations and DOA are not fully understood. Recently, we created a Drosophila model to study the pathogenesis of optic atrophy. Heterozygous mutation of Drosophila OPA1 (dOpa1) by P-element insertion results in no obvious morphological abnormalities, whereas homozygous mutation is embryonic lethal. In eye-specific somatic clones, homozygous mutation of dOpa1 causes rough (mispatterning) and glossy (decreased lens deposition) eye phenotypes in adult Drosophila. In humans, heterozygous mutations in OPA1 have been associated with mitochondrial dysfunction, which is predicted to affect multiple organs. In this study, we demonstrated that heterozygous dOpa1 mutation perturbs the visual function and an ERG profile of the Drosophila compound eye. We independently showed that antioxidants delayed the onset of mutant phenotypes in ERG and improved larval vision function in phototaxis assay. Furthermore, heterozygous dOpa1 mutation also caused decreased heart rate, increased heart arrhythmia, and poor tolerance to stress induced by electrical pacing. However, antioxidants had no effects on the dysfunctional heart of heterozygous dOpa1 mutants. Under stress, heterozygous dOpa1 mutations caused reduced escape response, suggesting abnormal function of the skeletal muscles. Our results suggest that heterozygous mutation of dOpa1 shows organ-specific pathogenesis and is associated with multiple organ abnormalities in an age-dependent and organ-specific manner.

Optic atrophy 1 (OPA1) is a dynamin-like GTPase located in the inner mitochondrial membrane and mutations in OPA1 are associated with autosomal dominant optic atrophy (DOA). OPA1 plays important roles in mitochondrial fusion, cristae remodeling and apoptosis. Our previous study showed that dOpa1 mutation caused elevated reactive oxygen species (ROS) production and resulted in damage and death of the cone and pigment cells in Drosophila eyes. Since ROS-induced oxidative damage to the cells is one of the primary causes of aging, in this study, we examined the effects of heterozygous dOpa1 mutation on the lifespan. We found that heterozygous dOpa1 mutation caused shortened lifespan, increased susceptibility to oxidative stress and elevated production of ROS in the whole Drosophila. Antioxidant treatment partially restored lifespan in the male dOpa1 mutants, but had no effects in the females. Heterozygous dOpa1 mutation caused an impairment of respiratory chain complex activities, especially complexes II and III, and reversible decreased aconitase activity. Heterozygous dOpa1 mutation is also associated with irregular and dysmorphic mitochondria in the muscle. Our results, for the first time, demonstrate the important role of OPA1 in aging and lifespan, which is most likely mediated through augmented ROS production.

Mutations in optic atrophy 1 (OPA1), a nuclear gene encoding a mitochondrial protein, is the most common cause for autosomal dominant optic atrophy (DOA). The condition is characterized by gradual loss of vision, color vision defects, and temporal optic pallor. To understand the molecular mechanism by which OPA1 mutations cause optic atrophy and to facilitate the development of an effective therapeutic agent for optic atrophies, we analyzed phenotypes in the developing and adult Drosophila eyes produced by mutant dOpa1 (CG8479), a Drosophila ortholog of human OPA1. Heterozygous mutation of dOpa1 by a P-element or transposon insertions causes no discernable eye phenotype, whereas the homozygous mutation results in embryonic lethality. Using powerful Drosophila genetic techniques, we created eye-specific somatic clones. The somatic homozygous mutation of dOpa1 in the eyes caused rough (mispatterning) and glossy (decreased lens and pigment deposition) eye phenotypes in adult flies; this phenotype was reversible by precise excision of the inserted P-element. Furthermore, we show the rough eye phenotype is caused by the loss of hexagonal lattice cells in developing eyes, suggesting an increase in lattice cell apoptosis. In adult flies, the dOpa1 mutation caused an increase in reactive oxygen species (ROS) production as well as mitochondrial fragmentation associated with loss and damage of the cone and pigment cells. We show that superoxide dismutase 1 (SOD1), Vitamin E, and genetically overexpressed human SOD1 (hSOD1) is able to reverse the glossy eye phenotype of dOPA1 mutant large clones, further suggesting that ROS play an important role in cone and pigment cell death. Our results show dOpa1 mutations cause cell loss by two distinct pathogenic pathways. This study provides novel insights into the pathogenesis of optic atrophy and demonstrates the promise of antioxidants as therapeutic agents for this condition., Competing Interests: Competing interests. The authors have declared that no competing interests exist.

The effect of chlorpromazine (CPZ) was studied at four different doses in a group of 10 normal subjects. Blood levels of CPZ were assayed by gas chromatography and showed wide interindividual variations. Spontaneous brain electrical activity (EEG) was recorded from 8 leads and submitted to spectral analysis. Evoked responses (ER) to flashes, pattern reversals and clicks were averaged, and measured by their amplitude and variability. Several subjects presented marked side-effects (responders, R) and showed differences in many EEG parameters with respect to subjects without side-effects (non-responders, NR). A cluster analysis permitted to distinguish very clearly these two groups of subjects. The differences in the effects of CPZ between the R and NR groups involved mainly EEG, and appeared with a systematic topography over the scalp. Within the R group, many differences were observed as a function of the dose of CPZ; they consisted mainly in a decrease of alpha and an increase of theta activity in the EEG, decrease of amplitude and increase of variability in the ER measures. These modifications had also a typical topography over the scalp. Finally, many variables of EEG (relative power only) were correlated with plasma level of CPZ, while no such correlation appeared for ER. These results are discussed in terms of individual sensitivity to drugs, relationships between EEG parameters and plasma level, and topographical differences in the effect of CPZ.

In order to define some principal clinical characteristics of the hospitalised depressives, the authors have examined a group of 100 depressed patients consecutively admitted to the Psychiatric University Clinic of Lausanne. The clinic is at the same time a sector hospital. The depressives constituted 21% of all hospitalised patients. The number of depressives admitted during the duration of the study (6 months) permitted to calculate a hospitalisation rate of 86 patients per 100 000 inhabitants and per year. The 100 patients were subclassified in patients with a short depressive reaction, neurotic depressives, and endogenous depressives. Each of the 3 subgroups had about the same size. A modified version of the ICD 9 was used for the diagnostic classification. As a whole, the patients showed serious psychiatric manifestations and the majority presented suicidal tendencies. Besides, there were found characteristics which are not considered to be associated with depressions in general: an elevated proportion of unmarried persons in the total group, psychopathic traits among the reactive and neurotic depressives, and a considerable proportion of parental loss in early childhood in these two last mentioned subgroups. Furthermore, an accumulation of chronic and therapy resistant cases was observed in the group of neurotic depressives. A third of the endogenous depressives had been resistant to the ambulatory antidepressive treatment; a part of these patients responded well to the treatment in the hospital.

Ten healthy volunteers were injected i.v. with 5 mg Ro 15-1788, a specific benzodiazepine antagonist, or placebo in a double-blind randomised design. In the EEG, Ro 15-1788 led--with some topographical variations--to a diminution of theta and alpha power, an increase of alpha mean frequency and a decrease of delta mean frequency. In auditory evoked potentials, the N1P2 and P2N2 amplitudes decreased. The electrophysiological changes induced by Ro 15-1788 are consistent with a central stimulant action. Ro 15-1788 induced some slight behavioural and subjective changes.

A group of 57 women, who had been hospitalised for puerperal psychiatric disorders from 1958 to 1977, were reexamined in 1982. The aim of the study was to determine the proportion of patients who had suffered from nonpuerperal psychotic relapses or other subsequent psychopathology, to define the sample diagnostically, taking into account progress in classification, to characterize the so far relatively neglected later course of illness, and to establish criteria related to relapse and global clinical outcome. Of these patients 65% had at least one nonpuerperal relapse, only 25% remained free of later psychopathology, but the global outcome was favorable or relatively favorable in many cases. Of the patients who had had nonpuerperal relapses 43% were classified as suffering from affective psychosis, as many as 38% from schizoaffective psychosis, and only 19% from schizophrenia. Schizoaffective psychosis seems to be particularly liable to be provoked by childbirth. No major evidence was found that endogenous psychoses with puerperal onset and nonpuerperal relapses have a course of illness different from that of the corresponding diagnostic category in general. Cases with exclusively puerperal decompensations seem to be nosologically independent from the traditionally recognized endogenous psychoses. Characteristics strongly related to nonpuerperal relapses were a family history of psychosis and the occurrence of psychotic episodes before the index episode. Puerperal relapses occurred at a much higher rate in patients who also had nonpuerperal relapses than in patients without.

Brain electrical activity changes induced by Ro 15-1788, an antagonist of central benzodiazepine effects, were investigated in 10 normal subjects. The diazepam-induced sedation, as ascertained by spontaneous EEG, was rapidly reversed after an intravenous injection of 5 mg Ro 15-1788. There appeared to be a good correlation between the EEG and evoked responses modifications; the decrease of the amplitude of the N2 wave may reflect an increase of alertness.

Conflicting results on the correlation of tricyclic levels in plasma and saliva have raised doubts about the clinical usefulness of monitoring these drugs in the latter body fluid. However, saliva drug levels may reflect the free plasma concentration, which possibly determines its level in the brain. In two groups of depressive patients, the evolution was studied of the levels of amitriptyline and nortriptyline in plasma (as free and total) and in saliva, after the administration of amitriptyline. The results show a poor correlation between total plasma and saliva concentration of amitriptyline and nortriptyline, respectively. Levels of both tricyclics in saliva exceed by far those measured in plasma dialysate. However, the relationship is such that free plasma concentrations may be predicted from those measured in saliva, if one takes into account saliva pH at the moment of collecting the sample.