New materials used for the synthesis of 2-chlorophenyl cyclopentyl ketone seized from an illicit ketamine manufacturing unit.

Ketamine deemed as a psychoactive substance has gained popularity for recreational use owing to its hallucinogenic and dissociative effects. Understanding the synthetic processes of ketamine can provide essential clues for law enforcement officers against illicit ketamine manufacturing. In this case report, a chemical company was being monitored by law enforcement officers due to its importation of precursors and materials that could be used for the synthesis of illicit drugs. After materials and products seized from this chemical company were employed for analyses using gas chromatography-mass spectrometry, liquid chromatography-high-resolution mass spectrometry, and nuclear magnetic resonance analyses, ketamine, hydroxylamine, 2-chlorophenyl cyclopentyl ketone, and cyclopentanone p-toluenesulfonylhydrazone were identified. In addition, a novel process for the synthesis of ketamine precursor 2-chlorophenyl cyclopentyl ketone from cyclopentanone p-toluenesulfonylhydrazone and 2-chlorobenzaldehyde was validated. This is the first report to uncover this novel process for the synthesis of 2-chlorophenyl cyclopentyl ketone and can be used to increase awareness among law enforcement officers and forensic practitioners about these novel starting materials for the synthesis of ketamine.

A critical role of a eubiotic microbiota in gating proper immunocompetence in Arabidopsis.

Although many studies have shown that microbes can ectopically stimulate or suppress plant immune responses, the fundamental question of whether the entire preexisting microbiota is indeed required for proper development of plant immune response remains unanswered. Using a recently developed peat-based gnotobiotic plant growth system, we found that Arabidopsis grown in the absence of a natural microbiota lacked age-dependent maturation of plant immune response and were defective in several aspects of pattern-triggered immunity. Axenic plants exhibited hypersusceptibility to infection by the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 and the fungal pathogen Botrytis cinerea. Microbiota-mediated immunocompetence was suppressed by rich nutrient conditions, indicating a tripartite interaction between the host, microbiota and abiotic environment. A synthetic microbiota composed of 48 culturable bacterial strains from the leaf endosphere of healthy Arabidopsis plants was able to substantially restore immunocompetence similar to plants inoculated with a soil-derived community. In contrast, a 52-member dysbiotic synthetic leaf microbiota overstimulated the immune transcriptome. Together, these results provide evidence for a causal role of a eubiotic microbiota in gating proper immunocompetence and age-dependent immunity in plants.

Roles of microbiota in autoimmunity in Arabidopsis.

Over the past three decades, researchers have isolated plant mutants that display constitutively activated defense responses in the absence of pathogen infection. These mutants are called autoimmune mutants and are typically dwarf and/or bearing chlorotic/necrotic lesions. From a genetic screen for Arabidopsis genes involved in maintaining a normal leaf microbiota, we identified TIP GROWTH DEFECTIVE 1 (TIP1), which encodes a S-acyltransferase, as a key player in guarding leaves against abnormal microbiota level and composition under high humidity conditions. The tip1 mutant has several characteristic phenotypes of classical autoimmune mutants, including a dwarf stature, displaying lesions, and having a high basal level of defense gene expression. Gnotobiotic experiments revealed that the autoimmune phenotypes of the tip1 mutant are largely dependent on the presence of microbiota as axenic tip1 plants have markedly reduced autoimmune phenotypes. We found that the microbiota dependency of autoimmune phenotypes is shared by several "lesion mimic"-type autoimmune mutants in Arabidopsis. Interestingly, autoimmune phenotypes caused by mutations in NLR genes do not require the presence of microbiota and can even be partially alleviated by microbiota. Our results therefore suggest the existence of two classes of autoimmunity (microbiota-dependent vs. microbiota-independent) in plants. The observed interplay between autoimmunity and microbiota in the lesion mimic class of autoimmunity is reminiscent of the interactions between autoimmunity and dysbiosis in the animal kingdom.

Doxycycline Ameliorates the Severity of Experimental Proliferative Vitreoretinopathy in Mice.

After successful surgeries for patients with rhegmatogenous retinal detachment, the most common cause of retinal redetachment is proliferative vitreoretinopathy (PVR), which causes severe vision impairment and even blindness worldwide. Until now, the major treatment for PVR is surgical removal of the epiretinal membrane, while effective treatment to prevent PVR is still unavailable. Therefore, we investigated the potential of doxycycline, an antibiotic in the tetracycline class, to treat PVR using a mouse model. We used the human retinal pigment epithelial cell line, ARPE-19, for in vitro and in vivo studies to test doxycycline for PVR treatment. We found that doxycycline suppressed the migration, proliferation, and contraction of ARPE-19 cells with reduced p38 MAPK activation and total MMP activity. Intravitreal doxycycline and topical tetracycline treatment significantly ameliorated the PVR severity induced by ARPE-19 cells in mice. PVR increased the expression of MMP-9 and IL-4 and p38 MAPK phosphorylation and modestly decreased IL-10. These effects were reversed by doxycycline and tetracycline treatment in the mouse retina. These results suggest that doxycycline will be a potential treatment for PVR in the future.

1-Aminocyclopropane-1-carboxylate (ACC) Deaminase Gene in Pseudomonas azotoformans Is Associated with the Amelioration of Salinity Stress in Tomato.

Although bacteria with 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity have been used to mitigate biotic and abiotic stresses in crops, it is not well known whether the ACC deaminase gene (acdS) in Pseudomonas azotoformans is related to the alleviation of salt stress by the bacterium. This study aimed to evaluate the effects of acdS in P. azotoformans strain CHB 1107 on the nutrient uptake and growth of tomato plants under salt stress. The acdS mutant (CHB 1107 M) of P. azotoformans CHB 1107 was obtained through bacterial conjugation. Wild-type (CHB 1107 WT) and CHB 1107 M were used to inoculate tomato plants grown in a soil or solution with an electrical conductivity of 6 dS/m adjusted by NaCl. CHB 1107 M completely lost the ability to produce ACC deaminase, whereas the complementation of acdS in CHB 1107 M preserved its ACC deaminase activity. CHB 1107 WT significantly reduced the production of ethylene and proline by tomato plants under salt stress, increasing the shoot and root dry weights of tomato plants compared with the noninoculated control and CHB 1107 M. In addition, tomato plants inoculated with CHB 1107 M showed a significant reduction in K (27.5%), Ca (23.0%), and Mn uptake (17.5%) compared with those inoculated with CHB 1107 WT. In contrast, CHB 1107 WT significantly reduced Na uptake by tomato plants in comparison to CHB 1107 M in saline soil conditions. In addition, the inoculation of tomato plants with CHB 1107 WT resulted in a higher K/Na ratio than in those inoculated with CHB 1107 M and the noninoculated control. These findings suggest that acdS in P. azotoformans is associated with the amelioration of salinity stress in tomato. Plant transformation with acdS and the field application of P. azotoformans may be used as potential management tools for crops under salt stress.

Suppression of the Reactive Oxygen Response Alleviates Experimental Autoimmune Uveitis in Mice.

Reactive oxygen species (ROS) are produced by host phagocytes and play an important role in antimicrobial actions against various pathogens. Autoimmune uveitis causes blindness and severe visual impairment in humans at all ages worldwide. However, the role of ROS in autoimmune uveitis remains unclear. We used ROS-deficient (Ncf1-/-) mice to investigate the role of ROS in experimental autoimmune uveitis (EAU). Besides, we also used the antioxidant N-acetylcysteine (NAC) treatment to evaluate the effect of suppression of ROS on EAU in mice. The EAU disease scores of Ncf1-/- mice were significantly lower than those of wild-type mice. EAU induction increased the levels of cytokines (interleukin (IL)-1α, IL-1ß, IL-4, IL-6, IL-12, IL-17, and tumor necrosis factor (TNF)-α) and chemokines (monocyte chemoattractant protein (MCP)-1) in the retinas of wild-type mice but not in those of Ncf1-/- mice. EAU induction enhanced the level of NF-κB activity in wild-type mice. However, the level of NF-κB activity in Ncf1-/- mice with EAU induction was low. Treatment with the antioxidant NAC also decreased the severity of EAU in mice with reduced levels of oxidative stress, inflammatory mediators, and NF-κB activation in the retina. We successfully revealed a novel role of ROS in the pathogenesis of EAU and suggest a potential antioxidant role for the treatment of autoimmune uveitis in the future.

Effects of immediately static loading on osteointegration and osteogenesis around 3D-printed porous implant: A histological and biomechanical study.

The 3D-printed porous implant is capable of achieving favorable osteointegration and osteogenesis in the absence of mechanical stimulation during the early healing period. The purpose of this study is to evaluate the impact of immediately static loading on bone osteointegration and osteogenesis around the 3D-printed porous implant. Thirty porous implants with optimal configuration were installed bilaterally into femurs of 15 rabbits. The Load group on the left side was applied the maximal initial load of 10 N offered by a diminutive and built-in loading device and the Non-load group was on the contralateral side. At 2, 4, and 8 weeks post-operatively, the explants were harvested for push-out test to measure the biological fixation strength. The quantity and quality of new bone were evaluated by the means of histological examination, Micro-CT and bone density analysis. Moreover, the animal data were integrated into finite element models to assess the biomechanics of peri-implant bone. The results indicated that the quantity, quality and biomechanical properties of the new bone increased and optimized along with the healing time. It also demonstrated that the immediately static loading increased the volume of new bone with inferior quality in 2 weeks after implantation and the adverse influence emerged gradually as time extended. Moreover, finite element results demonstrated that the early structures of new bone around porous implant were not suitable for functional loading. This study indicated the mineralization modes of distance osteogenesis and contact osteogenesis around the porous implant. Accordingly, the delay and progressive loading protocol was recommended.

Effect of Porous Microstructures on the Biomechanical Characteristics of a Root Analogue Implant: An Animal Study and a Finite Element Analysis.

BACKGROUND: Full ceramic or metal custom-made root analogue implants (RAIs) are made by replicating the natural tooth geometry. However, it may lead to the stress shielding of the surrounding bone, and an RAI is unable to easily achieve primary stability. Therefore, to improve primary stability and reduce stress shielding, RAI porous structures are proposed. The purpose of this study was to evaluate the effect of porous microstructures on the biomechanical characteristics of the custom-made RAI. METHODS: Porous and bulk titanium cylinders and porous RAI and conventional implants for in vivo tests were fabricated using a selective laser melting (SLM) technology. The elastic modulus and the compressive strength of porous titanium cylinders were evaluated. These samples were then implanted into rabbit femurs (cylinders) and beagle dog mandibles (RAI and conventional implants). A simplified three-dimensional geometry of the anterior maxilla of a patient was constructed. Then, based on the extracted standard template library (STL) data, five different RAI models were constructed: (A) smooth surface, (B) pit surface, (C) bulb surface, (D) threaded surface, and (E) porous surface. A conventional implant model was also constructed. A static load of 100 N was applied to the crown in the multivectoral direction. RESULTS: The results of the in vivo experiment confirmed that the porous structure decreased the elastic modulus of Ti6Al4V. Additionally, the implantation of the porous custom-made RAIs resulted in increased new bone ingrowth and decreased bone resorption compared to conventional implants. Moreover, the 3D finite element analysis suggested that the bone surrounding porous custom-made RAIs was subjected to a more uniform stress distribution, and the strain values of the surrounding bone were more conducive to bone formation. CONCLUSION: Based on these findings, a custom-made RAI with a porous surface accelerates bone formation and might reduce the stress-shielding effect.

Postoperative Mycobacteroides abscessus subsp. abscessus endophthalmitis: Clinical analysis of 12 clustered adults and a proposed therapeutic algorithm.

PURPOSE: Postoperative endophthalmitis caused by nontuberculous mycobacterium is a rare but devastating complication after intraocular surgery. However, optimal treatment strategies remain undetermined in view of its rarity. METHODS: We investigated the cases of culture-proven postoperative Mycobacteroides abscessus subsp. abscessus endophthalmitis in southern Taiwan, focusing on clinical manifestations and microbiological study, and aimed to describe clinical staging and to propose a therapeutic modality for this disease. RESULTS: Twelve cases, including two published cases, were treated in two medical centers in southern Taiwan between Aug. 2011 and Dec. 2016, and all ever received cataract surgery at one clinic. Their disease courses could be categorized into four distinct stages, i.e., the initial, quiescent, recurrent, and end stage, and some cases experienced 1-4 cycles of quiescent-recurrent stages. Although all eyes ended up with phthisis or were eviscerated, the affected eyes receiving pars plana vitrectomy (PPV) tended to become quiescent and survived longer than those without PPV (adjusted hazard ratio: 13.9, p < 0.05). Eight isolates of eight patients were available for microbiological study. All isolates were susceptible to amikacin, and inducible clarithromycin resistance was observed in 100% of isolates. CONCLUSION: Despite the preservation of vision in postoperative M.abscessus endophthalmitis remained a challenge, a stage-based approach is proposed, which may facilitate decision-makings for the future study.

Plant-Microbe Interactions Facing Environmental Challenge.

In the past four decades, tremendous progress has been made in understanding how plants respond to microbial colonization and how microbial pathogens and symbionts reprogram plant cellular processes. In contrast, our knowledge of how environmental conditions impact plant-microbe interactions is less understood at the mechanistic level, as most molecular studies are performed under simple and static laboratory conditions. In this review, we highlight research that begins to shed light on the mechanisms by which environmental conditions influence diverse plant-pathogen, plant-symbiont, and plant-microbiota interactions. There is a great need to increase efforts in this important area of research in order to reach a systems-level understanding of plant-microbe interactions that are more reflective of what occurs in nature.

Biomechanical comparison of implant inclinations and load times with the all-on-4 treatment concept: a three-dimensional finite element analysis.

The purpose of this study was to compare the effects of implant inclinations and load times on stress distributions in the peri-implant bone based on immediate- and delayed-loading models. Four 3D FEA models with different inclination angle of the posterior implants (0°, 15°, 30°, 45°) were constructed. A static load of 150 N in the multivectoral direction was applied unilaterally to the cantilever region. The stress distributions in the peri-implant bone were evaluated before and after osseointegration. The principal tensile stress (σmax), mean principal tensile stress (σmax), principal compressive stress (σmin) and mean principal compressive stress (σmin) of the bone and micromotion at the contact interface between the bone and implants were calculated. In all the models, peak principal stresses occurred in the bone surrounding the left tilted implant. The highest σmax and σmin were all observed in the 0° model for both immediate- and delayed-loading models. And the 0° and 15° models showed higher σmax and σmin values. The 0°models showed the largest micromotion. The observed stress distribution was better in the 30° and 45° models than in the 0° and 15° models.

First report of bovine viral diarrhea virus and Mycobacterium avium subspecies paratuberculosis infection in Tibetan sheep (Ovis aries) in Tibetan Plateau, China.

Bovine viral diarrhea virus (BVDV) and Mycobacterium avium subspecies paratuberculosis (MAP) are important pathogens, which cause serious disease in animals. However, information about BVDV and MAP infection in Tibetan sheep in China is limited. Two thousand one hundred and eighty-seven blood samples were collected from Tibetan sheep between April 2013 and March 2014 from the Tibetan Plateau and tested for BVDV and MAP antibodies using commercial ELISA kits. The overall seroprevalence of BVDV and MAP in Tibetan sheep was 36.7 and 11.29%, respectively. Furthermore, risk factor analysis indicated that the age of sheep was statistically significant associated with BVDV infection and the region was considered as the risk factor of MAP infection in sheep (P < 0.05), gender and season were not considered as risk factors. This is the first report of seroprevalence and risk factors associated with BVDV and MAP infection in Tibetan Sheep in China, which will provide baseline information for controlling BVDV and MAP infection in ruminants in the Tibetan Plateau, western China.

Author Correction: Major ocular trauma in Taiwan: 2002-2004 versus 2012-2014.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Major ocular trauma in Taiwan: 2002-2004 versus 2012-2014.

We investigated the temporal changes in major eye injuries in Taiwan by reviewing the medical records of all patients with ocular trauma hospitalized at the National Cheng Kung University Hospital during 2002-2004 and 2012-2014. A total of 169 eyes (161 patients) during 2002-2004 and 121 eyes (120 patients) during 2012-2014 were enrolled (mean ± SD age: 41.9 ± 20.8 years in 2002-2004, and 51.8 ± 19.3 years in 2012-2014). Males accounted for ~75% of patients. The most frequent injury-causing object was metallic material (~24%), and blunt traumas were most frequently attributable to traffic accidents and falls. The most common locations of injuries for males and females were the workplace and home, respectively. Open-globe injuries occurred in ~70% of eyes, requiring primary repair, cataract extraction, and/or intraocular lens implantation. The frequencies of fall injury, lacrimal system laceration, lens injury, corneal/scleral foreign bodies, and use of intracameral antibiotics increased from 2002-2004 to 2012-2014, while those of closed-globe injury, vitreous haemorrhage, optic nerve injury, and medical treatment decreased. The final visual acuity remained poor (≤20/200) in >1/3 of injured eyes. Despite therapeutic advancements, major eye injuries still pose a high risk for poor visual outcome.

Real-world use of ranibizumab for neovascular age-related macular degeneration in Taiwan.

This study investigated the "real-world" use of ranibizumab for neovascular age-related macular degeneration (nAMD) in Taiwan and assessed the visual outcome. We reviewed the medical records at National Cheng Kung University Hospital, Taiwan, during 2012-2014 for 264 consecutive eyes of 229 patients with nAMD, who applied for ranibizumab covered by national health insurance. A total of 194 eyes (73.5%) in 179 patients (65.5% men; mean ± standard deviation age 69.4 ± 10.7 years) were pre-approved for treatment. Applications for treatment increased year by year, but approval rates decreased during this time. The major causes of rejection for funding were diseases mimicking nAMD, including macular pucker/epiretinal membrane, macular scarring, dry-type AMD, and possible polypoidal choroidal vasculopathy. After completion of three injections in 147 eyes, visual acuity significantly improved, gaining ≥1 line in 51.8% of eyes and stabilising in 38.3% of 141 eyes in which visual acuity was measured. The 114 eyes approved with only one application had a better visual outcome than the 27 eyes approved after the second or third applications. In conclusion, ranibizumab is effective for nAMD; however, approval after the second or third application for national health insurance cover is a less favourable predictor of visual outcome.

Motorized injector-assisted intrascleral intraocular lens fixation.

For eyes with deficient capsular support, intraocular lens (IOL) implantation has long been a technical challenge. Recently, intrascleral fixation of the haptics of a three-piece posterior chamber IOL has become a popular option. In this procedure, externalization of the leading haptic during IOL injection is a stressful step. We present a modified technique to improve the ease and safety of this step. Our modified technique involves IOL injection with a motorized injector with several important modifications described here. With these modifications, a surgeon can easily maintain the correct orientation of the IOL in a well-controlled manner during IOL injection. The records of 13 patients who underwent this technique were retrospectively evaluated. Corrected-distance visual acuity improved significantly after surgery (p<0.05). No postoperative retinal detachment, endophthalmitis, IOL decentration, or vitreous hemorrhage was noted during the follow-up period. In conclusion, the motorized injector-assisted intrascleral IOL fixation technique is a safe and effective alternative to the conventional procedure. This technique makes the process of leading haptic externalization easier and more controllable.

Airbag-Associated Severe Blunt Eye Injury Causes Choroidal Rupture and Retinal Hemorrhage: A Case Report.

A case of choroidal rupture caused by airbag-associated blunt eye trauma and complicated with massive subretinal hemorrhage and vitreous hemorrhage that was successfully treated with intravitreal injection of expansile gas and bevacizumab is presented. A 53-year-old man suffered from loss of vision in his right eye due to blunt eye trauma by a safety airbag after a traffic accident. On initial examination, the patient had no light perception in his right eye. Dilated ophthalmoscopy revealed massive subretinal hemorrhage with macular invasion and faint vitreous hemorrhage. We performed intravitreal injection of pure sulfur hexafluoride twice for displacement, after which visual acuity improved to 0.03. For persistent subretinal hemorrhage and suspicion of choroidal neovascularization (CNV), intravitreal bevacizumab (1.25 mg/0.05 mL) injection was administered. After 3 weeks, the visual acuity of his right eye recovered to 0.4. For early-stage choroidal rupture-induced subretinal hemorrhage and complications of suspected CNV, intravitreal injection of expandable gas and intraocular injection of antiangiogenesis drugs seem to be an effective treatment.

Isolates and antibiotic susceptibilities of endophthalmitis in postcataract surgery: a 12-year review of culture-proven cases.

The purpose of this study was to investigate the spectrum of organisms causing endophthalmitis after cataract surgery in a tertiary medical center in Taiwan and the antibiotic susceptibilities. This was a retrospective case series study. Patients with endophthalmitis after cataract surgery from January 2004 to July 2015 were reviewed. The outcome measures included the identification of isolates, antibiotic susceptibilities, and final visual outcomes. Twenty-one organisms were isolated from 19 cases. The most common organisms were Enterococcus in 38.1 %, especially Enterococcus faecalis, followed by Staphylococcus epidermidis in 28.6 % and Staphylococcus aureus in 9.5 %. All of the Gram-positive isolates tested were susceptible to vancomycin (100 %), and ceftazidime and amikacin were susceptible for Gram-negative organisms. The Gram-positive organisms remain to be the predominant cause of postoperative endophthalmitis, and Enterococcus species has had an increasing incidence. Vancomycin is still the most powerful antibiotic for Gram-positive organisms, while ceftazidime and amikacin are effective for Gram-negative bacteria.

A new approach of operating room management in a general public hospital with multiple wholly-owned campuses / 中华护理杂志

Objective To explore a new approach of operating room (OR) management to ensure quality of care for surgical patients in a general public hospital with wholly-owned campuses. Methods The three-grade manageri-al structure for operating room was established,unified quality management was conducted in three campuses. Uni-fied training system was established to ensure the same level of professional competence among nurses. Highly flex-ible human resources allocation plan was performed for better staff rotation arrangement. Depending on information integration system,operation schedules of surgeons at all campuses were taken into consideration. Through instruments linkage among campuses,cost control was accomplished via scientific performance allocation mechanism. Results There was no statistically significant difference both in nursing quality scores and work satisfaction level of sur-geons for OR nurses among three campuses (P>0.05). The acquisition cost of instruments was reduced by 1.7048 million Yuan. Conclusion The new approach of operating room management guaranteed the quality of nursing care for surgical patients in three campuses,saved labor and financial cost in OR.

Two Redundant Receptor-Like Cytoplasmic Kinases Function Downstream of Pattern Recognition Receptors to Regulate Activation of SA Biosynthesis.

Salicylic acid (SA) serves as a critical signaling molecule in plant defense. Two transcription factors, SARD1 and CBP60g, control SA biosynthesis through regulating pathogen-induced expression of Isochorismate Synthase1, which encodes a key enzyme for SA biosynthesis. Here, we report that Pattern-Triggered Immunity Compromised Receptor-like Cytoplasmic Kinase1 (PCRK1) and PCRK2 function as key regulators of SA biosynthesis. In the pcrk1 pcrk2 double mutant, pathogen-induced expression of SARD1, CBP60g, and ICS1 is greatly reduced. The pcrk1 pcrk2 double mutant, but neither of the single mutants, exhibits reduced accumulation of SA and enhanced disease susceptibility to bacterial pathogens. Both PCRK1 and PCRK2 interact with the pattern recognition receptor FLS2, and treatment with pathogen-associated molecular patterns leads to rapid phosphorylation of PCRK2. Our data suggest that PCRK1 and PCRK2 function downstream of pattern recognition receptor in a signal relay leading to the activation of SA biosynthesis.