The pheromone darcin drives a circuit for innate and reinforced behaviours.

Organisms have evolved diverse behavioural strategies that enhance the likelihood of encountering and assessing mates1. Many species use pheromones to communicate information about the location, sexual and social status of potential partners2. In mice, the major urinary protein darcin-which is present in the urine of males-provides a component of a scent mark that elicits approach by females and drives learning3,4. Here we show that darcin elicits a complex and variable behavioural repertoire that consists of attraction, ultrasonic vocalization and urinary scent marking, and also serves as a reinforcer in learning paradigms. We identify a genetically determined circuit-extending from the accessory olfactory bulb to the posterior medial amygdala-that is necessary for all behavioural responses to darcin. Moreover, optical activation of darcin-responsive neurons in the medial amygdala induces both the innate and the conditioned behaviours elicited by the pheromone. These neurons define a topographically segregated population that expresses neuronal nitric oxide synthase. We suggest that this darcin-activated neural circuit integrates pheromonal information with internal state to elicit both variable innate behaviours and reinforced behaviours that may promote mate encounters and mate selection.

Constitutive and conditional epitope-tagging of endogenous G protein coupled receptors in Drosophila.

To visualize the cellular and subcellular localization of neuromodulatory G-protein coupled receptors (GPCRs) in Drosophila, we implement a molecular strategy recently used to add epitope tags to ionotropic receptors at their endogenous loci. Leveraging evolutionary conservation to identify sites more likely to permit insertion of a tag, we generated constitutive and conditional tagged alleles for Drosophila 5-HT1A, 5-HT2A, 5-HT2B, Octß1R, Octß2R, two isoforms of OAMB, and mGluR. The conditional alleles allow for the restricted expression of tagged receptor in specific cell types, an option not available for any previous reagents to label these proteins. We show expression patterns for these receptors in female brains, and that 5-HT1A and 5-HT2B localize to the mushroom bodies and central complex respectively, as predicted by their roles in sleep. By contrast, the unexpected enrichment of Octß1R in the central complex and of 5-HT1A and 5-HT2A to nerve terminals in lobular columnar cells in the visual system suggest new hypotheses about their functions at these sites. Using an additional tagged allele of the serotonin transporter, a marker of serotonergic tracts, we demonstrate diverse spatial relationships between postsynaptic 5-HT receptors and presynaptic 5-HT neurons, consistent with the importance of both synaptic and volume transmission. Finally, we use the conditional allele of 5-HT1A to show that it localizes to distinct sites within the mushroom bodies as both a postsynaptic receptor in Kenyon cells and a presynaptic autoreceptor.Significance Statement In Drosophila, despite remarkable advances in both connectomic and genomic studies, antibodies to many aminergic GPCRs are not available. We have overcome this obstacle using evolutionary conservation to identify loci in GPCRs amenable to epitope-tagging, and CRISPR/Cas9 genome editing to generate eight novel lines. This method may also be applied to other GPCRs and allows cell-specific expression of the tagged receptor. We have used the tagged alleles we generated to address several questions that remain poorly understood. These include the relationship between pre- and postsynaptic sites that express the same receptor, and the use of relatively distant targets by presynaptic release sites that may employ volume transmission as well as standard synaptic signaling.

Removal of Intraocular Foreign Bodies Using a Modified Flute Needle.

PURPOSE: To describe the construction of a novel intraocular snare and evaluate its effectiveness in intraocular foreign body (IOFB) removal. METHOD: This is a retrospective consecutive case series. Five patients underwent pars plana vitrectomy and IOFB removal using the intraocular snare constructed from modified flute needle. RESULTS: All IOFBs were successfully engaged and removed with the snare on the first attempt. Three of the 5 cases (60%) enjoyed good visual outcome (0.4-1.0) postoperatively. No complication related to the use of the snare was encountered in this case series. CONCLUSION: Intraocular foreign body snare is simple, safe, and effective in IOFB removal.

Are we facing an increasing surgical demand for high myopic traction maculopathies? A 12-year study from Hong Kong.

PURPOSE: We aimed to investigate the longitudinal change in the number of surgically operated myopic traction maculopathies (MTM) cases at a tertiary eye centre. METHODS: A retrospective study of all consecutive cases of surgically operated MTM over 12 years (2009-2020) was conducted in a myopia prevalent region. We compared outcomes among three groups: (1) myopic macular hole (MH), (2) myopic macular hole with retinal detachment (MHRD), and (3) myopic foveoschisis with retinal detachment (MFRD). RESULTS: Fifty-one cases were included in the study (8 cases of MH, 33 cases of MHRD and 10 cases of MFRD). The overall mean age was 63.8 +/- 8.7 with a female preponderance (2:1). The mean age of the MH group (58.6) was significantly younger than the MHRD group (64.2) and MFRD group (66.6) (p = 0.02). Subgroup analysis using ATN classification did not show its correlation with both visual improvement and anatomical success. When comparing the first 6-year period (2009-2014) with the second 6-year period (2015-2020), there was a significant increase in the number of cases (p = 0.01). CONCLUSION: We observe an increase in the number of surgically operated MTM. This follows the trend of the global rise in the prevalence of myopia and baby boomers entering retirement.

Association between endoscopic cyclophotocoagulation and vitreous prolapse in trabeculectomy: a case report.

BACKGROUND: To propose that possible alteration or damage to the ciliary zonules during uncomplicated endoscopic cyclophotocoagulation (ECP) can cause complications in subsequent filtration surgery. CASE PRESENTATION: We present two cases with uncomplicated primary combined phacoemulsification and ECP that underwent subsequent trabeculectomy. Both cases were complicated with vitreous prolapse during the trabeculectomy procedure. We review the anatomy of the ciliary zonules and their spatial relationship with the ciliary processes targeted during ECP and propose an association between ECP, zonular damage and complications in subsequent trabeculectomy such as vitreous prolapse. CONCLUSIONS: Damage to ciliary zonules during ECP may not manifest until subsequent glaucoma filtration surgery. In patients who received prior ECP, we may consider taking preventative measures to avoid associated complications such as vitreous prolapse. Patients with known risk factors for weak zonules may consider choosing alternative intraocular pressure-lowering means.

Laser-assisted LED for adaptive-driving-beam headlights employing ultra-reliable single crystal phosphor for autonomous vehicles.

A novel laser-assisted LED for adaptive-driving-beam (ADB) headlights employing an ultra-reliable Ce3+: YAG-based single crystal phosphor (SCP)-converter layer for use in autonomous vehicles is demonstrated. The SCP fabricated at a high-temperature of 1,940°C exhibited better thermal stability than other phosphor-converter materials, evidenced by a thermal aging test. The high-beam pattern of the ADB is measured at a luminous intensity of 88,436 cd at 0°, 69,393 cd at ± 2.5°, and 42,942 cd at ± 5°, which well satisfies the ECE R112 class B regulation. The advantage of introducing the laser-assisted LED system employing the highly reliable SCP is to produce the high intensity for the ADB, which enables the increase of the field of view by 20% and the brightness by 28% for the ADB headlight and results in improving the visibility from ± 7° to ± 8.5° and the illumination distance up to 200 m. This proposed advance ADB headlight with the ultra-reliable SCP and the novel laser-assisted LED is favorable as one of the most promising ADB light source candidates for use in the next-generation autonomous vehicle applications.

Detection of SARS-CoV-2 in conjunctival secretions from patients without ocular symptoms.

PURPOSE: To evaluate the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in conjunctival secretions from patients without ocular symptoms. METHODS: Conjunctival swabs were prospectively collected from laboratory-confirmed Coronavirus disease 2019 (COVID-19) patients without ocular symptoms for reverse transcription-polymerase chain reaction (RT-PCR) and viral culture. RESULTS: A total of 158 conjunctival swabs were obtained from 49 laboratory-confirmed COVID-19 patients. The median duration of illness when the first conjunctival swab was obtained was 10 days (range 2-27 days). Four conjunctival swabs from four different patients (4/49, 8.2%) were positive for SARS-CoV-2 RNA by RT-PCR. The Ct values ranged from 32.7 to 37.7 (mean 35.4). Viral cultures were negative for all four RT-PCR-positive conjunctival swabs. CONCLUSION: Conjunctival secretions of a minority of COVID-19 patients without ocular symptoms may contain relatively low levels of SARS-CoV-2 RNA, but their infectiousness remains undetermined. Appropriate infection control measures should be implemented during ophthalmological assessment of COVID-19 patients to prevent potential nosocomial transmission of SARS-CoV-2.

The Implications of COVID-19 to Ophthalmology.

The coronavirus disease 2019 (COVID-19) pandemic has brought unprecedented challenges to ophthalmology. At least 16 ophthalmologists worldwide have succumbed to COVID-19. It reflects the susceptibility of ophthalmologists to COVID-19 infection as they are in close proximity to patients. This chapter provides an overview of the ocular manifestations of COVID-19, risks of COVID-19 to ophthalmologists and patients, clinical service adjustments due to COVID-19, and infection control measures to minimize the transmission of COVID-19 in ophthalmic practice.

The use of short message service (SMS) to reduce outpatient attendance in ophthalmic clinics during the coronavirus pandemic.

PURPOSE: In order to minimize the risk of transmission of coronavirus disease 2019 (COVID-19), many clinic appointments were postponed to lower patient attendance. Actively calling patients to postpone appointments is a labour-intensive process. We were the first ophthalmic clinics in Hong Kong to use short message service (SMS) to dispatch messages simultaneously to a large number of patients to offer postponement of appointments. The aim of this study is to evaluate whether SMS is an effective method to reduce outpatient attendance during the COVID-19 pandemic. METHODS: This is an observational study reviewing data on SMS messages sent to all patients attending ophthalmology clinics of a tertiary eye centre in Hong Kong. All SMS were sent at least 5 days before the scheduled appointments. The text message included an enquiry hotline for postponement of appointments and offered drug refill. The study included data from February to April 2020. Two hundred patients were invited to take part in a questionnaire on satisfaction level and reason(s) for appointment rescheduling. RESULTS: During the study period, a total of 17,028 SMS were sent. The overall response rate was 23.6%. 14.3% postponed their appointments. This led to an overall 13.9% reduction of clinic attendance. The overall satisfaction was high (96%). The main reason for postponing appointment was worries about infection risk (93.1%). CONCLUSION: SMS was an efficient and cost-effective flow-control method which was well accepted by patients and can reduce outpatient attendance. The time saved can potentially allow healthcare workers to conduct other infection control measures during the COVID-19 pandemic.

Differential Tropism of SARS-CoV and SARS-CoV-2 in Bat Cells.

Severe acute respiratory syndrome coronavirus 2 did not replicate efficiently in 13 bat cell lines, whereas severe acute respiratory syndrome coronavirus replicated efficiently in kidney cells of its ancestral host, the Rhinolophus sinicus bat, suggesting different evolutionary origins. Structural modeling showed that RBD/RsACE2 binding may contribute to the differential cellular tropism.

Possible Bat Origin of Severe Acute Respiratory Syndrome Coronavirus 2.

We showed that severe acute respiratory syndrome coronavirus 2 is probably a novel recombinant virus. Its genome is closest to that of severe acute respiratory syndrome-related coronaviruses from horseshoe bats, and its receptor-binding domain is closest to that of pangolin viruses. Its origin and direct ancestral viruses have not been identified.

The use of personal protective equipment in clinical ophthalmology during corona virus disease-2019: a review of international guidelines and literature.

PURPOSE OF REVIEW: The use of nonpharmaceutical interventions can prevent viral spread in COVID-19 pandemic and PPE forms a crucial part of this strategy. However, there are discrepancies in existing guidelines and a lack of consensus among ophthalmic communities. This review aims to identify general consensus and provides recommendation of PPE for most common ophthalmological scenarios. With a global shortage of PPE, extended use and reuse strategies are also discussed. RECENT FINDINGS: In this review, guidelines and resources were selected, based on a three-tier process. The first-tier resources were from international infection control organizations. The second-tier resources were from ophthalmological professional associations and colleges. The third-tier resources involved a PubMed search using the keywords 'COVID-19; coronavirus; personal protective equipment' performed on 1 May 2020. Non-English guidelines and literatures were excluded. SUMMARY: On the basis of our methodology, we included a total of 30 documents, including 5 resources from tier 1, 14 resources from tier 2 and 15 from tier 3. Different levels of protection are necessary. Whenever performing an aerosol generating procedure, maximum protection should be ensured, this includes FFP3 respirator, fluid resistant gown, goggles or face-shield and disposable gloves. Similar protection should be used for handling COVID-19-positive/suspected case but the use of FFP2 respirator is acceptable. During routine outpatient clinic in cases of negative triage, it is recommended to use ASTM III surgical mask, plastic apron, disposable gloves and eye protection with goggles or face-shield. Lastly, patients should be encouraged to wear surgical masks whenever possible.

Stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from Hong Kong.

PURPOSE: Coronavirus disease (COVID-19) has rapidly emerged as a global health threat. The purpose of this article is to share our local experience of stepping up infection control measures in ophthalmology to minimise COVID-19 infection of both healthcare workers and patients. METHODS: Infection control measures implemented in our ophthalmology clinic are discussed. The measures are based on detailed risk assessment by both local ophthalmologists and infection control experts. RESULTS: A three-level hierarchy of control measures was adopted. First, for administrative control, in order to lower patient attendance, text messages with an enquiry phone number were sent to patients to reschedule appointments or arrange drug refill. In order to minimise cross-infection of COVID-19, a triage system was set up to identify patients with fever, respiratory symptoms, acute conjunctivitis or recent travel to outbreak areas and to encourage these individuals to postpone their appointments for at least 14 days. Micro-aerosol generating procedures, such as non-contact tonometry and operations under general anaesthesia were avoided. Nasal endoscopy was avoided as it may provoke sneezing and cause generation of droplets. All elective clinical services were suspended. Infection control training was provided to all clinical staff. Second, for environmental control, to reduce droplet transmission of COVID-19, installation of protective shields on slit lamps, frequent disinfection of equipment, and provision of eye protection to staff were implemented. All staff were advised to measure their own body temperatures before work and promptly report any symptoms of upper respiratory tract infection, vomiting or diarrhoea. Third, universal masking, hand hygiene, and appropriate use of personal protective equipment (PPE) were promoted. CONCLUSION: We hope our initial experience in stepping up infection control measures for COVID-19 infection in ophthalmology can help ophthalmologists globally to prepare for the potential community outbreak or pandemic. In order to minimise transmission of COVID-19, ophthalmologists should work closely with local infection control teams to implement infection control measures that are appropriate for their own clinical settings.

A Rapid, Simple, Inexpensive, and Mobile Colorimetric Assay COVID-19-LAMP for Mass On-Site Screening of COVID-19.

To control the COVID-19 pandemic and prevent its resurgence in areas preparing for a return of economic activities, a method for a rapid, simple, and inexpensive point-of-care diagnosis and mass screening is urgently needed. We developed and evaluated a one-step colorimetric reverse-transcriptional loop-mediated isothermal amplification assay (COVID-19-LAMP) for detection of SARS-CoV-2, using SARS-CoV-2 isolate and respiratory samples from patients with COVID-19 (n = 223) and other respiratory virus infections (n = 143). The assay involves simple equipment and techniques and low cost, without the need for expensive qPCR machines, and the result, indicated by color change, is easily interpreted by naked eyes. COVID-19-LAMP can detect SARS-CoV-2 RNA with detection limit of 42 copies/reaction. Of 223 respiratory samples positive for SARS-CoV-2 by qRT-PCR, 212 and 219 were positive by COVID-19-LAMP at 60 and 90 min (sensitivities of 95.07% and 98.21%) respectively, with the highest sensitivities among nasopharyngeal swabs (96.88% and 98.96%), compared to sputum/deep throat saliva samples (94.03% and 97.02%), and throat swab samples (93.33% and 98.33%). None of the 143 samples with other respiratory viruses were positive by COVID-19-LAMP, showing 100% specificity. Samples with higher viral load showed shorter detection time, some as early as 30 min. This inexpensive, highly sensitive and specific COVID-19-LAMP assay can be useful for rapid deployment as mobile diagnostic units to resource-limiting areas for point-of-care diagnosis, and for unlimited high-throughput mass screening at borders to reduce cross-regional transmission.

Neurocognitive function, performance status, and quality of life in pediatric intracranial germ cell tumor survivors.

BACKGROUND: Intracranial germ cell tumors (GCT) are more common in Asia than in the West, accounting for about 15% of brain tumors in Asian children. The survival rate for intracranial GCT is excellent, but there are concerns about the effects of radiotherapy on neuropsychological function and quality of life of patients. METHODS: Intracranial germ cell tumors (GCT) are more common in Asia than in the West, accounting for about 15% of brain tumors in Asian children. The survival rate for intracranial GCT is excellent, but there are concerns about the effects of radiotherapy on neuropsychological function and quality of life of patients. Intracranial GCT survivors in Hong Kong aged ≥ 6 years who received cranial irradiation in the past 15 years were recruited. Neurocognitive function and performance status were assessed by the Hong Kong Wechsler Intelligence scale and Karnofsky/Lansky performance scales (KPS), respectively. Quality of life was assessed using the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales. A chart review was performed for tumor characteristics and complications related to the tumor and its treatment. RESULTS: Twenty-five intracranial GCT survivors were recruited. Longer length of time since treatment was associated with lower IQ scores. Larger tumor size was associated with lower KPS scores. Hemiparesis, poor manual dexterity, and complications with multi-organ involvement were associated with significantly lower KPS scores. Higher irradiation dosage was associated with lower PedsQL physical scores. CONCLUSIONS: The majority of GCT survivors had average intellectual functioning, satisfactory performance status and relatively good quality of life, except in the physical aspect. Comprehensive evaluation and long-term follow-up of GCT survivors are essential to provide timely support and improve long-term outcomes.

Phacoemulsification cataract surgery in patients receiving novel oral anticoagulant medications.

INTRODUCTION: An increasing number of patients are taking novel oral anticoagulant (NOAC) medication, making perioperative management in phacoemulsification surgery an important issue. This study reports the haemorrhagic complications of NOAC in phacoemulsification surgery. DESIGN: Retrospective case study over a 4-year period. METHODS: Consecutive cases receiving NOAC during the time of phacoemulsification were reviewed. Patients were either advised to continue medications (continued group) or withhold medications before surgery (withheld group). MAIN OUTCOME MEASURES: Details including patient demographics, preoperative assessment, postoperative outcome and intraoperative, postoperative and systemic complications were recorded. RESULTS: A total of 20,100 cases of phacoemulsification were performed. Of which, 66 cases were found to be on NOAC (0.33%). This included 66 eyes of 53 patients, with 42 continued and 24 withheld medications before surgery. There was no statistically significant difference between the two groups in demographics, cataract risk factors, baseline renal function, clotting profile, type of NOAC, incision size, phacoemulsification energy, preoperative and postoperative visual acuity. There was also no significant difference in intraoperative, postoperative and systemic complications (p = 1.00 and 0.53, Fischer's exact test). None of the patients in the continued group had postoperative complications; two cases in the withheld group receiving retrobulbar anaesthesia had bruising and subconjunctival haemorrhage after resumption of NOAC (p = 0.13, Fischer's exact test). CONCLUSION: The present study found no difference in haemorrhagic complications between cases continuing and withholding NOAC during phacoemulsification. Nevertheless, the potential risks and benefits to continue or withhold NOAC perioperatively should be carefully considered via a multidisciplinary approach.

Retrospective review on the outcome and safety of transscleral diode laser cyclophotocoagulation in refractory glaucoma in Chinese patients.

PURPOSE: Transscleral cyclodiode laser cyclophotocoagulation (TSCP) is often reserved for treatment of refractory glaucoma. This retrospective study investigates the safety and efficacy of TSCP among the Chinese population. METHODS: A retrospective review was performed on electronic patient records of all patients receiving TSCP between years 2009 to year 2016. Patient demographics, indication for laser, success and response rate, change in intraocular pressure (IOP), number of treatment sessions, laser energy, glaucoma medication, visual acuity, pain symptoms and complication rate were documented. RESULTS: The study included 126 patients: 81 patients were male and 45 were female, and the mean age was 66.6 ± 14.3 years old and the mean follow-up was 22.7 ± 14.1 months. The mean number of treatment sessions was 1.5 ± 0.8. The success rate was 67.3%. The mean IOP before TSCP was 67 ± 38.6 mmHg and 22.8 ± 14.2 mmHg after TSCP, the mean IOP reduction was 38.4%, which was statistically significant (P value < 0.001, Wilcoxon signed rank test). The mean laser energy used per eye was 72.7 ± 56.6 and 49.2 ± 22.9 J per individual treatment session. The mean number of laser shots was 15.0 ± 6.1. 71% of patients were able to reduce their glaucoma medication after TSCP, (P value < 0.01, Wilcoxon signed rank test). 86.1% of patients had improvement in pain symptoms after TSCP. The overall complication rate was 7.1%. CONCLUSION: TSCP was found to be safe and effective among the Chinese population, with comparably low laser energy setting and complication rate. It was found to be most effective in treatment of glaucoma due to trauma, acute angle closure, uveitis and chronic angle closure.

Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding.

Although bats are known to harbor Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to MERS-CoV in most genome regions, its spike protein occupies a phylogenetic position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Because Ty-BatCoV HKU4 but not Pi-BatCoV HKU5 can use the MERS-CoV receptor human dipeptidyl peptidase 4 (hDPP4) for cell entry, we tested the ability of Hp-BatCoV HKU25 to bind and use hDPP4. The HKU25-receptor binding domain (RBD) can bind to hDPP4 protein and hDPP4-expressing cells, but it does so with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for entry to hDPP4-expressing cells, although with lower efficiency than that of MERS-spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest that bat CoV spike proteins may have evolved in a stepwise manner for binding to hDPP4.