Crosstalk between presynaptic trafficking and autophagy in Parkinson's disease.

Parkinson's disease (PD) is a debilitating neurodegenerative disorder that profoundly affects one's motor functions. The disease is characterized pathologically by denervation of dopaminergic (DAergic) nigrostriatal terminal and degeneration of DAergic neurons in the substantia nigra par compacta (SNpc); however, the precise molecular mechanism underlying disease pathogenesis remains poorly understood. Animal studies in both toxin-induced and genetic PD models suggest that presynaptic impairments may underlie the early stage of DA depletion and neurodegeneration (reviewed in Schirinzi, T., et al. 2016). Supporting this notion, human genetic studies and genomic analysis have identified an increasing number of PD risk variants that are associated with synaptic vesicle (SV) trafficking, regulation of synaptic function and autophagy/lysosomal system (Chang, D., et al. 2017, reviewed in Trinh, J. & Farrer, M. 2013; Singleton, A.B., et al. 2013). Although the precise mechanism for autophagy regulation in neurons is currently unclear, many studies demonstrate that autophagosomes form at the presynaptic terminal (Maday, S. & Holzbaur, E.L. 2014; Vanhauwaert, R., et al. 2017; reviewed in Yue, Z. 2007). Growing evidence has revealed overlapping genes involved in both SV recycling and autophagy, suggesting that the two membrane trafficking processes are inter-connected. Here we will review emergent evidence linking SV endocytic genes and autophagy genes at the presynaptic terminal. We will discuss their potential relevance to PD pathogenesis.

Antimicrobial blue light therapy for multidrug-resistant Acinetobacter baumannii infection in a mouse burn model: implications for prophylaxis and treatment of combat-related wound infections.

In this study, we investigated the utility of antimicrobial blue light therapy for multidrug-resistant Acinetobacter baumannii infection in a mouse burn model. A bioluminescent clinical isolate of multidrug-resistant A. baumannii was obtained. The susceptibility of A. baumannii to blue light (415 nm)-inactivation was compared in vitro to that of human keratinocytes. Repeated cycles of sublethal inactivation of bacterial by blue light were performed to investigate the potential resistance development of A. baumannii to blue light. A mouse model of third degree burn infected with A. baumannii was developed. A single exposure of blue light was initiated 30 minutes after bacterial inoculation to inactivate A. baumannii in mouse burns. It was found that the multidrug-resistant A. baumannii strain was significantly more susceptible than keratinocytes to blue light inactivation. Transmission electron microscopy revealed blue light-induced ultrastructural damage in A. baumannii cells. Fluorescence spectroscopy suggested that endogenous porphyrins exist in A. baumannii cells. Blue light at an exposure of 55.8 J/cm(2) significantly reduced the bacterial burden in mouse burns. No resistance development to blue light inactivation was observed in A. baumannii after 10 cycles of sublethal inactivation of bacteria. No significant DNA damage was detected in mouse skin by means of a skin TUNEL assay after a blue light exposure of 195 J/cm(2).

[Endophytic bacterial diversity of wild soybean (Glycine soja) varieties with different resistance to soybean cyst nematode (Heterodera glycines)].

OBJECTIVE: The aim of this study was to investigate endophytic bacterial diversity of wild soybean varieties with different resistance to soybean cyst nematode(Heterodera glycines) , for deciphering the interactions of soybean cyst nematode with endophytic bacteria. METHODS: After screening wild soybean varieties against race 3 of H. glycines, we investigated endophytic bacterial diversity in root tissues of wild soybean varieties with different resistance to H. glycines using 16S rDNA cloning library and amplified ribosomal DNA restriction analysis. RESULTS: Endophytic bacteria of wild soybean root belonged to 6 bacterial groups, the clones belonging to group Proteobacteria and Firmicutes were the endophyte dominants in wild soybean with 46.8% and 13.6% of total clones, respectively. Actinobacteria, Bacteroidetes, Acidobacteria, Deincoccus-Thermus and Archaea were less represented. 18.8% of clone sequences were similar to those of uncultured bacteria in the environment. The bacterial diversity was higher in H. glycines-Resistant than -Susceptible wild soybean varieties, and the dominant group was different between H. glycines-Resistant and -Susceptible wild soybean varieties. Mesorhizobium tamadayense, Enterobacter ludwigii and Bacillus megaterium were the main bacterial groups in special operational taxonomic units (OTUs) of H. glycines-Resistant wild soybean variety. CONCLUSIONS: By 16S rDNA cloning library and amplified ribosomal DNA restriction analysis, the diversity of dominant group of endophytic bacteria in root tissues has difference among H. glycines-Resistant and -Susceptible wild soybean varieties.

Effect of Soybean Monoculture on the Bacterial Communities Associated with Cysts of Heterodera glycines.

The soybean cyst nematode (SCN), Heterodera glycines, can cause significant reductions in soybean yield and quality in many parts of the world. Natural biological control may play an important role in regulating SCN population. In this study the bacterial communities associated with SCN cysts obtained from fields under different lengths of soybean monoculture were explored. Soil samples were collected in 2010 and 2011 from six fields that had been used for soybean monoculture for 2 to 41 yr. SCN population densities were determined and bacterial communities from SCN cysts were investigated by Biolog and PCR-DGGE methods. SCN population densities initially increased in the first 5 yr of soybean monoculture but then declined steeply as years of soybean monoculture increased. Catabolic diversity of bacterial communities associated with cysts tended to decline as number of years of monoculture increased. Some specific PCR-DGGE bands, mainly representing Streptomyces and Rhizobium, were obtained from the cysts collected from the long-term monoculture fields. Principal component analysis of Biolog and PCR-DGGE data revealed that bacterial communities associated with cysts could be divided into two groups: those from cysts obtained from shorter (< 8 yr) vs. longer (> 8 yr) monoculture. This research demonstrates that the composition of the bacterial communities obtained from SCN cysts changes with length of soybean monoculture; the suppressive impact of these bacterial communities to SCN is yet to be determined.

Neural stem/progenitor cell-derived extracellular vesicles: A novel therapy for neurological diseases and beyond.

As bilayer lipid membrane vesicles secreted by neural stem/progenitor cells (NSCs), NSC-derived extracellular vesicles (NSC-EVs) have attracted growing attention for their promising potential to serve as novel therapeutic agents in treatment of neurological diseases due to their unique physicochemical characteristics and biological functions. NSC-EVs exhibit advantages such as stable physical and chemical properties, low immunogenicity, and high penetration capacity to cross blood-brain barrier to avoid predicaments of the clinical applications of NSCs that include autoimmune responses, ethical/religious concerns, and the problematic logistics of acquiring fetal tissues. More importantly, NSC-EVs inherit excellent neuroprotective and neuroregenerative potential and immunomodulatory capabilities from parent cells, and display outstanding therapeutic effects on mitigating behavioral alterations and pathological phenotypes of patients or animals with neurological diseases. In this review, we first comprehensively summarize the progress in functional research and application of NSC-EVs in different neurological diseases, including neurodegenerative diseases, acute neurological diseases, dementia/cognitive dysfunction, and peripheral diseases. Next, we provide our thoughts on current limitations/concerns as well as tremendous potential of NSC-EVs in clinical applications. Last, we discuss future directions of further investigations on NSC-EVs and their probable applications in both basic and clinical research.

Preparation of Ru/N-doped carbon catalysts by induction of different nitrogen source precursors for the hydroprocessing of lignin oil.

The lignin oil produced by rapid pyrolysis of lignin is considered a promising liquid fuel source. Hydrodeoxygenation (HDO) is a kind of efficient method to upgrade the lignin oil, and a high-performance catalyst is key to the hydrodeoxygenation of lignin oil. In this study, a high dispersion and small size Ru nanoparticle loaded N-doped carbon catalyst was derived by the direct pyrolysis of a mixture of ruthenium trichloride and melamine, and it could efficiently convert lignin oil. The lignin oil was completely transformed at 240 °C and 1 MPa H2, and 36.58% cyclohexane was obtained. The formation, surface area, and nitrogen species of the catalyst could be controlled by changing the precursor of the nitrogen-doped carbon support. The percentage of pyridine nitrogen possessed with melamine as a nitrogen-carbon precursor (31.35%) was much higher than that with urea (16.47%) and dicyandiamide (8.20%) as nitrogen-carbon precursors. The presence of pyridine nitrogen could not only serve as the coordination site for even dispersity and stability of Ru nanoparticles but also regulated the electron density of Ru nanoparticles (NPs) and increased the active site Ru0 through electron transfer.

HCN channel inhibitor induces ketamine-like rapid and sustained antidepressant effects in chronic social defeat stress model.

Repeated, long-term (weeks to months) exposure to standard antidepressant medications is required to achieve treatment efficacy. In contrast, acute ketamine quickly improves mood for an extended time. Recent work implicates that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are involved in mediating ketamine's antidepressant effects. In this study, we directly targeted HCN channels and achieved ketamine-like rapid and sustained antidepressant efficacy. Our in vitro electrophysiological recordings first showed that HCN inhibitor DK-AH 269 (also called cilobradine) decreased the pathological HCN-mediated current (Ih) and abnormal hyperactivity of ventral tegmental area (VTA) dopamine (DA) neurons in a depressive-like model produced by chronic social defeat stress (CSDS). Our in vivo studies further showed that acute intra-VTA or acute systemic administration of DK-AH 269 normalized social behavior and rescued sucrose preference in CSDS-susceptible mice. The single-dose of DK-AH 269, both by intra-VTA microinfusion and intraperitoneal (ip) approaches, could produce an extended 13-day duration of antidepressant-like efficacy. Animals treated with acute DK-AH 269 spent less time immobile than vehicle-treated mice during forced swim test. A social behavioral reversal lasted up to 13 days following the acute DK-AH 269 ip injection, and this rapid and sustained antidepressant-like response is paralleled with a single-dose treatment of ketamine. This study provides a novel ion channel target for acutely acting, long-lasting antidepressant-like effects.

[Diversity of bacteria isolated from cysts Heterodera glycines in Heilongjiang].

OBJECTIVE: To understand the bacterial diversity isolated from the cysts of Heterodera glycines in the soybean field in Heilongjiang Province. METHODS: Bacteria were isolated from cysts on nutrient agar plates using dilution plate method and further identified by phylogenetic analysis based on 16S rDNA gene sequences. RESULTS: Totally 90 bacteria strains with different colony morphology were selected on nutrient agar plate and their phylogenetic features were analyzed based on the partial 16S rDNA sequences. In total 7 genera and 22 species were identified, including 46 strains in Gammaproteobacteria (51.1%), 32 in Firmicutes (35.6%), 10 in Betaproteobacteria (11.1%), and 2 in Alphaproteobacteria (2.2%). The dominant bacteria species were Pseudomonas and Bacillus. CONCLUSION: There was abundant species diversity of bacteria isolated from cysts Heterodera glycines in Heilongjiang, and these bacteria may play a physical and ecological roles in nematodes.

A systematic review and meta-analysis of the factors associating the willingness of Chinese community residents to receive COVID-19 vaccine.

BACKGROUND: Amid the coronavirus disease of 2019 (COVID-19) pandemic, China's vaccination campaign is progressing in an orderly manner. In the process of vaccination, the vaccination rates in different parts of China are different, and the factors affecting people's vaccination are also different, which may be caused by some reasons affecting people's willingness to vaccinate or complex sociodemographic characteristics factors. We found that inconsistent findings on factors associated with willingness to get COVID-19 vaccination in available studies. Therefore, we conducted a meta-analysis of current factors influencing people's willingness to receive COVID-19 vaccination to assess the associated factors influencing people's COVID-19 vaccination. METHODS: The databases of CNKI, Chinese Biomedical Literature (CBM), Wanfang, VIP, PubMed, Web of Science, and Cochrane Library were searched by computer to collect the relevant literature on the factors affecting the willingness of Chinese community residents to undergo COVID-19 vaccination. After extracting the data, RevMan 5.3 and R software were used for statistical analysis. Population included in the study were Chinese community residents; outcome indicators were associated factors of willingness to get COVID-19 vaccination; COVID-19, odds ratio (OR), confidence interval (CI). Study designs were Cross-sectional study. Egger's tests was used to check potential publication bias. RESULTS: The willingness to get COVID-19 vaccination of community residents who think COVID-19 vaccine is effective is 4.10 times that of community residents who think COVID-19 vaccine is ineffective (OR =4.10, 95% CI: 3.08-5.46), and community residents who think COVID-19 vaccine is safe are 1.82 times more willing to receive COVID-19 vaccine than those who think COVID-19 vaccine is unsafe (OR =1.82, 95% CI:1.42-2.33); the willingness to get COVID-19 vaccination of community residents who think COVID-19 infection risk is high was 1.53 times that of community residents who think COVID-19 infection risk is low (OR =1.53, 95% CI: 1.43-1.64); the willingness of male community residents to vaccinate COVID-19 is 1.48 times higher than that of female community residents (OR =1.48, 95% CI: 1.23-1.76). CONCLUSIONS: The finding means that vaccination strategies need to be formulated according to the gender of community residents, propaganda of vaccination information, and dissemination of epidemic information to achieve higher levels of COVID-19 vaccination.

Enhancing deep mineralization of refractory benzotriazole via carbon nanotubes-intercalated cobalt copper bimetallic oxide nanosheets activated peroxymonosulfate process: Mechanism, degradation pathway and toxicity.

Peroxymonosulfate-based advanced oxidation processes (PMS-AOPs) are effective methods for the degradation of highly toxic and refractory nitrogen-containing heteroatomic pollutants such as benzotriazole (BTA). The construction of catalytic materials with multiple active centers is the key to generating abundant reactive oxygen species (ROS) and achieving high mineralization efficiency in PMS-AOPs. Herein, carbon nanotubes-intercalated cobalt copper bimetallic oxide nanosheets catalyst (CoCuNS@CNTs) was obtained by pyrolysis of two-dimensional (2D) MOF precursor. The degradation rate constant of BTA in CoCuNS@CNTs/PMS system was 4 times higher than that of metal oxide nanosheets catalyst without CNTs, while exhibiting high cycling stability and mineralization efficiency. Serial characterizations demonstrated that CoCu nanosheets was formed by CNTs-induced the directional assembly of metal oxide nanoparticles, which had high graphitization and abundant oxygen vacancies and could greatly facilitated the adsorption and electron transfer between the catalyst, PMS and BTA. Moreover, the doping of Cu species significantly improved PMS utilization and accelerated the Co(III)/Co(II) redox cycle. Both radicals (SO4-• and •OH) and non-radicals (1O2) played a role in CuCoNS@CNTs/PMS system and the contributions of ROS were 72.2%, 11.1% and 16.7%, respectively. Meanwhile, the concentration of key ROS (SO4-•) production increased from 4.76 µM to 8.56 µM compared with cobalt oxide nanosheets (CoNS). Three degradation pathways of BTA were proposed: benzene ring opening, benzene ring hydroxylation and triazole ring dimerization. Finally, the toxicity changes during the degradation process were measured and the toxicity of eleven intermediates was evaluated. This study may provide new insights into the degradation of persistent organic pollutants.

[Comparative analysis of pathological structure between acute closed and open Achilles tendon rupture].

OBJECTIVE: To investigate the morphological, histological and ultrastructural changes of acute closed rupture of Achilles tendon, in order to clarify the pathological basis of the injury and to explore the significance. METHODS: From January 2015 to January 2019, 35 patients with acute Achilles tendon rupture who underwent the minimally invasive Achilles tendon suture technique were retrospectively analyzed. Among these patients, 12 cases in acute open Achilles tendon rupture group included 10 males and 2 females, with an average age of (35.1±9.7) years old ranging from 19 to 50, and the time from injury to operation was 2 to 8 hours with an average of(5.6±1.8);23 cases in acute closed Achilles tendon rupture group included 21 males and 2 females, with an average age of (35.5±6.6) years old ranging from 18 to 50, and the time from injury to operation was 3 to 15 hours with an average of (7.5±3.1). The gross appearance and imaging findings of the broken end of Achilles tendon tissue in the two groups were compared by naked eye observation and foot and ankle MRI at 4 to 6 hours before operation. HE staining, scanning and fluoroscopic electron microscopy, immunohistochemistry(Sirius red staining) were performed on the intraoperative Achilles tendon tissue specimens at 1 to 2 days after operation, the collagen fiber degeneration and local fat infiltration, collagen fiber shape, cell morphology and function, and the distribution of typeⅠand type Ⅲ collagen fibers in Achilles tendon were compared between the two groups. RESULTS: Compared with the acute open Achilles tendon rupture group, the acute closed Achilles tendon rupture group had poor elasticity, hard texture, moderate edema, irregular shape of Achilles tendon broken end, horsetail shape, and more calcification around the broken end. HE staining results:the collagen fibers in the Achilles tendon of the acute open Achilles tendon rupture group were arranged irregularly, with hyaline degeneration and fat infiltration;The results of electron microscopy showed that collagen arranged disorderly and fibroblasts atrophied in the acute closed Achilles tendon rupture group. Immunohistochemical(Sirius staining) results:the proportion of collagenⅠin the acute open Achilles tendon rupture group and the acute closed Achilles tendon rupture group was(91.12±4.34)% and(54.71±17.78)% respectively, and the proportion of collagen Ⅲ was (8.88±4.34)% and (45.29±17.78)% respectively. The content of collagenⅠin the acute closed Achilles tendon rupture group was lower than that in the acute open Achilles tendon rupture group, and the content of collagen Ⅲ in the acute closed Achilles tendon rupture group was higher than that in the acute open Achilles tendon rupture group(P<0.05). CONCLUSION: The morphology, histology and ultrastructure of the acute closed ruptured Achilles tendon are significantly altered compared with the normal Achilles tendon. The original fine and orderly spatial structure cannot be maintained, part of collagen Ⅰ is replaced by collagen Ⅲ, and the toughness and strength of the tendon tissue decreased, which may be the feature of degeneration of the Achilles tendon and an important pathological basis for closed Achilles tendon rupture.

Spiderweb-inspired all-weather CoS quantum dots confined in N-doped carbon for boosted sulfate radical evolution.

Inspired by the working principle of natural spiderweb and long-persistence phosphors, we have synthesized a spiderweb-like nanocomposite in which CoS quantum dots are confined in N-doped carbon frameworks/carbon nanotubes (CNTs). The intimate combination of three-dimensional conductive networks of CoS/CNTs with abundant active sites allows effective capture of sulfate radicals via both physical confinement and chemical bonding and accelerates the redox kinetics significantly. Furthermore, in virtue of the light storing and luminescence behaviors of long-persistence phosphors, the all-weather CoS/CNTs produced can realize an optimum degradation efficiency of 64% under dark conditions. Overall, this work reveals a significant step forward for building a desirable all-weather catalyst with abundant active sites for potential use in degradation under dark conditions.

[Research progress in osteonecrosis of femoral head following femoral intertrochanteric fractures in adults].

OBJECTIVE: To summarize the research progress of osteonecrosis of femoral head (ONFH) following femoral intertrochanteric fractures in adults. METHODS: Relevant literature at home and abroad was extensively reviewed to summarize the pathogenesis, high-risk factors, and treatment of ONFH after femoral intertrochanteric fracture in adults. RESULTS: ONFH after femoral intertrochanteric fracture mostly occurs within 2 years after operation, with a lower incidence. At present, it is believed that comminuted and large displacement fractures caused by high-energy injuries, fracture line close to the base of neck, excessive external rotation deformity, improper intramedullary nail entry points, and rough intraoperative manipulating may injury the deep branch of the medial circumflex femoral artery, causing ONFH. Hip replacement is the main treatment for necrosis, which can achieve good results. CONCLUSION: Addressing the above risks, excessive external rotation, overstretching, and rough manipulating should be avoided. Anatomical reduction should be performed during the operation, the nail entry point should be accurate and avoid repeated drilling and thermally bone necrosis.

Simultaneous and Efficient Production of Furfural and Subsequent Glucose in MTHF/H2O Biphasic System via Parameter Regulation.

Efficient production of furfural from cornstalk in 2-Methyltetrahydrofuran/aqueous (MTHF/H2O) biphasic system via parameter regulation (e.g., VMTHF/VH2O, temperature, time, and H2SO4 concentration) was proposed. The resulting solid residues achieved from the different MTHF/H2O system conditions for furfural production were also to prepare glucose by adding cellulases to increase the high-value applications of cornstalk. A maximum furfural yield (68.1%) was obtained based on reaction condition (VMTHF:VH2O = 1:1, 170 °C, 60 min, 0.05 M H2SO4). Among these parameters, the concentration of H2SO4 had the most obvious effect on the furfural production. The glucose yields of the residues acquired from different MTHF/H2O processes were enhanced and then a maximum value of 78.9% based on the maximum furfural production conditions was observed. Single factor may not be sufficient to detail the difference in glucose production, and several factors affected the hydrolysis efficiency of the residues. Overall, the MTHF/H2O system effectively converted cornstalk into furfural and glucose via a simple and environment-friendly process, thus was an ideal manner for the food industries.

Author Correction: Midbrain circuit regulation of individual alcohol drinking behaviors in mice.

The original version of this Article contained an error in the spelling of the author Scott Edwards, which was incorrectly given as Scott Edward. This has now been corrected in both the PDF and HTML versions of the Article.

Enhancement of riboflavin production by overexpression of acetolactate synthase in a pta mutant of Bacillus subtilis.

Genetic alterations of carbon flux into the acetoin biosynthesis pathway as a possible means to reduce acid accumulation were investigated in the riboflavin-producing Bacillus subtilis during growth on glucose. The lower rates of cell growth and riboflavin production were found in the pta-disrupted mutant while the rate of acetate formation was reduced. In contrast, acid accumulation was significantly reduced, to one-fifth that of the parental strain RH33::[pRB63](n), and a 50% increase in the riboflavin yield was obtained when the expression of the gene encoding acetolactate synthase was increased in the pta-disrupted mutant. Metabolic analysis, together with enzyme activity assays, indicated that the tricarboxylic acid cycle fluxes are significantly increased in response to acetolactate synthase overexpression in pta-disrupted mutant. Moreover, the intracellular ATP-to-ADP ratio also increased 5.8-fold. The high concentration of ATP could explain the increased riboflavin production.

Comparison of clinical outcomes in all-arthroscopic versus mini-open repair of rotator cuff tears: A randomized clinical trial.

BACKGROUND: The aim of the study was to compare the clinical outcomes of patients undergoing all-arthroscopic (AA) or mini-open (MO) rotator cuff repair. METHODS: The present study evaluated 50 patients who had undergone AA repair and 50 patients who had undergone MO repair with a minimum 1-year follow-up. Every patient was asked to complete the Disabilities of the Arm, Shoulder and Hand (DASH) and visual analog scale (VAS) questionnaires. Constant-Murley score (CMS) and active ranges, forward flexion and external rotation, were also evaluated and documented. One year after surgery, ultrasound evaluation was done to determine the integrity of the rotator cuff for each patient. RESULTS: The average age of enrolled patients at the time of surgery was 53.0 years (range, 40-59 years), and average follow-up was 16.6 months (range, 12-24 months). At 2 weeks, the range of forward flexion in the AA group was larger than that in the MO group (136.5 ±â€Š10.2 vs 132.5 ±â€Š7.7, P = 0.03). On postoperative day 1, the VAS in the MO group was significantly higher than that in the AA group (6.5 ±â€Š0.6 vs 6.1 ±â€Š0.6, P < 0.01). At 1 month, the difference in VAS between both groups reappeared (2.9 ±â€Š0.6 vs 2.6 ±â€Š0.6, P = 0.03). At 1 month, the CMS score of patients in the AA group was higher than that in the MO group (52.8 ±â€Š3.6 vs 50.9 ±â€Š5.0, P = 0.03). At 3 and 6 months, the DASH score of patients in the AA group was lower than that in the MO group (43.8 ±â€Š8.2 vs 47.8 ±â€Š4.4, P < 0.01 and 38.6 ±â€Š4.3 vs 42.7 ±â€Š9.9, P < 0.01, respectively). Mean operative time was longer in the AA group compared with that in the MO group (71.9 ±â€Š17.6 vs 64.7 ±â€Š12.7 minutes, P < 0.01). Five patients (10.0%) in the AA group and 4 patients (8.2%) in the MO group had rotator cuff retear, and 6 patients (12.0%) in the AA group and 8 patients (16.3%) in the MO group had adhesive capsulitis by the end of follow-up. There is no significant difference between the 2 groups in the incidence of complications. We also found that joint exercising at least 3 times per week was associated with better short- and long-term joint function recovery. CONCLUSIONS: The AA approach was associated with less pain and lower DASH score as well as higher CMS score in the early recovery period. No difference was found between the 2 groups in primary and secondary outcomes in the long term, or incidence of complications such as adhesive capsulitis and rotator cuff retear. In conclusion, we consider that the AA procedure has better recovery at short-term follow-ups, while both techniques are equivalent regarding long-term outcomes.

Multidimensional Approaches for A Case of Severe Adult Obsessive - Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a chronic, distressing and substantially impairing neuropsychiatric disorder, characterized by obsessions or compulsions. The current case describes a 44-year-old adult female diagnosed with OCD. The patient had an incomplete response to several SSRIs alone during her past treatment, and led a poor-quality life for at least three years. Current multidimensional approaches, including combined cognitive behavioral therapy (CBT) and the Selective Serotonin Reuptake Inhibitor (SSRI, Sertraline) with a small dose of antipsychotics (Aripiprazole) for augmentation, as well as familial support and resources from the internet were provided for the patient for six months. Standardized assessments with Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) every two months indicated significant reductions in obsessive and compulsive symptoms, with significant improvements in her social functioning and quality of life. A case such as this one provides preliminary support to multidimensional approaches for OCD treatment in order to achieve an optimal response, though further rigorous clinical trials are needed to provide more evidence.

Midbrain circuit regulation of individual alcohol drinking behaviors in mice.

Alcohol-use disorder (AUD) is the most prevalent substance-use disorder worldwide. There is substantial individual variability in alcohol drinking behaviors in the population, the neural circuit mechanisms of which remain elusive. Utilizing in vivo electrophysiological techniques, we find that low alcohol drinking (LAD) mice have dramatically higher ventral tegmental area (VTA) dopamine neuron firing and burst activity. Unexpectedly, VTA dopamine neuron activity in high alcohol drinking (HAD) mice does not differ from alcohol naive mice. Optogenetically enhancing VTA dopamine neuron burst activity in HAD mice decreases alcohol drinking behaviors. Circuit-specific recordings reveal that spontaneous activity of nucleus accumbens-projecting VTA (VTA-NAc) neurons is selectively higher in LAD mice. Specifically activating this projection is sufficient to reduce alcohol consumption in HAD mice. Furthermore, we uncover ionic and cellular mechanisms that suggest unique neuroadaptations between the alcohol drinking groups. Together, these data identify a neural circuit responsible for individual alcohol drinking behaviors.