Efficacy of Normalising Serum Zinc Level for Patients with Olfactory Dysfunction and Zinc Deficiency.

INTRODUCTION: Zinc deficiency may worsen the severity of olfactory dysfunction; however, the relationship between serum zinc levels and therapeutic effects on olfactory dysfunction remains uncertain. This study investigated the relationship between normalising serum zinc levels and the therapeutic effects on olfactory dysfunction. METHODS: Forty-two patients diagnosed with post-infectious, posttraumatic, and idiopathic olfactory dysfunction, with serum zinc levels < 70 µg/dL, were included in the study. All patients were treated with mecobalamin, tokishakuyakusan, and polaprezinc. The patients were divided into 2 groups: the zinc-normalised (≥ 70 µg/dL) and zinc-deficient (< 70 µg/dL) groups, based on their post-treatment serum zinc levels. Olfactory test results were compared in each of the 2 groups. RESULTS: The patients were treated for a median of 133 days. The zinc-normalised group had significantly better results in all olfactory tests (detection/recognition thresholds of the T&T olfactometer, odour identification test (Open Essence), visual analogue scale for olfactory dysfunction, self-administered odour questionnaire). In contrast, only the self-administered odour questionnaire showed a significant improvement in the zinc-deficient group, with no significant differences observed in the other olfactory tests. When comparing the changes in the olfactory test scores between the 2 groups, significant differences were observed in the detection/recognition thresholds of the T&T and Open Essence results. CONCLUSION: These findings suggest that patients with olfactory dysfunction may have difficulty improving their olfactory function if they also have zinc deficiency. Furthermore, normalisation of zinc deficiency may contribute to the improvement of olfactory dysfunction with general treatment.

Characteristics of higher depressive tendency in the patients with olfactory disorder.

OBJECTIVE: Most patients with olfactory dysfunction experience stress and anxiety because of the inconvenience and changes caused by the loss of olfaction. However, psychological assessment is not performed routinely in patients with olfactory dysfunction, and the characteristics of these patients with psychological depression are unclear. METHODS: In this study, we used the Self-rating Depression Scale to evaluate the degree of depression in patients who visited our clinic with olfactory dysfunction and examine the characteristics of these patients with strong depressive tendencies. Patients who visited our clinic between April 2019 and March 2020 with complaints of olfactory dysfunction were included in the study. RESULTS: A total of 180 patients (79 male and 101 female) underwent olfactory examination and completed the Self-rating Depression Scale. Eighty-six and 94 patients were included in the low depression and high depression groups, respectively. Binomial logistic regression analysis showed significant positive associations of Self-rating Depression Scale scores with female sex and the presence of parosmia/phantosmia (p < 0.05). CONCLUSION: In our study, approximately half of the patients with olfactory dysfunction had depressive tendencies especially in female and parosmia/phantosmia patients. We believe that psychological assessments, such as that with the SDS, can help identify patients with olfactory dysfunction who may be at a greater risk of developing depression.

Difference in the Dynamics of Antibody Titers between COVID-19 Vaccination and SARS-CoV-2 Infection in Healthcare Workers - A Case Study Based on Long-Term and Densely Repeated Measurements of Antibody Titers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is prevalent worldwide, and effective and safe vaccines against this virus have been developed. Although trends in antibody titers after vaccination and/or SARS-CoV-2 infection have been reported, long-term studies with high frequency of measurements are limited. This report describes the long-term and detailed trends in the antibodies against SARS-CoV-2 S protein receptor-binding domain (S-RBD) measured repeatedly after vaccination and/or infection in 3 healthcare workers. All healthcare workers were administered 30 µg of the messenger RNA vaccine, BNT162b2, during all vaccinations. The peak value of the SARS-CoV-2 S-RBD titer was reached at 1-2 weeks after vaccination and then decreased by half within 8 weeks after vaccination; the peak values of the antibody titer increased with repeated vaccinations. In contrast, after SARS-CoV-2 infection, the peak value of the antibody titer was reached at 4-8 weeks after infection, and the antibody titer remained elevated up to 16-40 weeks after the peak. This report describes the long-term and detailed trends in the anti-SARS-CoV-2 S-RBD titers, showing different patterns after vaccination and/or SARS-CoV-2 infection.

Impact of energy intake on the activities of daily living in patients with cervical spinal cord injury undergoing post-acute rehabilitation.

OBJECTIVE: To investigate the association between sufficient energy intake and improvement in activities of daily living (ADL) after hospitalization in patients with cervical spinal cord injury (CSCI) undergoing post-acute rehabilitation. DESIGN: Retrospective cohort study. SETTING: Post-acute care hospital from September 2013 to December 2020. PARTICIPANTS: Patients with CSCI admitted to a post-acute care hospital for rehabilitation. INTERVENTION: Not applicable. OUTCOME MEASURE(S): Multiple regression analysis was performed to investigate the relationship of sufficient energy intake to Motor Functional Independence Measure (mFIM) gain, mFIM score at discharge, and body weight change during hospitalization. RESULTS: In total, 116 patients (104 men and 12 women), median age: 55 (interquartile range [IQR] 41-65) years were included in the analysis. Then, 68 (58.6%) were in the energy-sufficient group, and 48 (41.4%) patients were classified under the energy-deficient group. The two groups did not significantly differ in terms of mFIM gain and mFIM score at discharge. The energy-sufficient group maintained body weight change during hospitalization than the energy-deficient group (0.6 [-2.0-2.0] vs. -1.9 [-4.0--0.3], P < 0.001). Multiple regression analysis showed no association between sufficient energy intake and outcomes. CONCLUSION: Sufficient energy intake within the first 3 days of admission did not affect ADL improvement during hospitalization in patients with a post-cute CSCI undergoing rehabilitation.

Two new species of Eriococcidae (Hemiptera: Coccomorpha) in Japan.

Two new felt scale species (Hemiptera: Coccomorpha: Eriococcidae) collected in Japan, Acanthococcus torikurai Tanaka sp. nov. and Anophococcus koguchii Tanaka sp. nov., are described and illustrated based on the morphological characteristics of the adult females. Acanthococcus torikurai is similar to A. spiraeae Borchsenius 1949 but lacks small pores on hind legs, spinulae on the meso- and metathoracic coxae, a cauda on abdominal segment VIII and capitate ventral setae. Anophococcus koguchii is similar to An. socialis (Goux 1931) but differs in having seven-segmented antennae, two different sizes of macrotubular ducts on the venter, multilocular pores mostly with five loculi rather than seven or eight, and in lacking large pores on the metathoracic coxae and a cauda on abdominal segment VIII. A key to the 17 Eriococcidae species found in Japan is also provided.

Long-Term Safety and Efficacy of Mirogabalin for Central Neuropathic Pain: A Multinational, Phase 3, 52-Week, Open-Label Study in Asia.

INTRODUCTION: Central neuropathic pain (CNeP) is difficult to treat and has diverse etiology, including spinal cord injury (CNePSCI), Parkinson's disease (CNePPD), and central post-stroke pain (CPSP). The safety and efficacy of mirogabalin have been demonstrated in short-term trials, including patients with CNePSCI. The objective of our study was to confirm the safety/efficacy of mirogabalin in patients with CNePPD and CPSP, and obtain long-term data for CNePSCI. METHODS: This 52-week, open-label extension of a previous randomized controlled study was conducted across Japan, Korea, and Taiwan. Patients with CNePSCI, CNePPD, or CPSP received twice daily (BID) 5-10 mg mirogabalin for a 4-week titration period, after which the dosage was maintained for 47 weeks at a maximum of 15 mg BID, followed by a 1-week taper period receiving the same dose but only administered once daily. The primary endpoint was safety, assessed primarily by incidence and severity of treatment-emergent adverse events (TEAEs). Efficacy was assessed in a post hoc analysis of data obtained by the short-form McGill Pain Questionnaire (SF-MPQ). RESULTS: Of the 210 patients enrolled, 106, 94, and 10 had CNePSCI, CPSP, and CNePPD, respectively. The mean overall age of patients was 62.9 years, and most patients were male and of Japanese ethnicity. TEAEs occurred in 84.8% of patients, the most common being somnolence (16.7%), peripheral edema (12.4%), edema (11.4%), nasopharyngitis (11.0%), and dizziness (7.6%). Most TEAEs were mild. Severe and serious TEAEs occurred in 6.2% and 13.3% of patients, respectively. All patient groups experienced reductions in SF-MPQ visual analog scores for pain: mean ± standard deviation changes from baseline at week 52 were -2.3 ± 21.13 mm (CNePSCI), -17.0 ± 24.99 mm (CPSP), and -17.1 ± 35.32 mm (CNePPD). CONCLUSION: Mirogabalin was generally safe, well tolerated, and effective for treatment of CNeP in this long-term study. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03901352.

Rapid and Robust Multi-Phenotypic Assay System for ALS Using Human iPS Cells with Mutations in Causative Genes.

Amyotrophic lateral sclerosis (ALS) is a major life-threatening disease caused by motor neuron degeneration. More effective treatments through drug discovery are urgently needed. Here, we established an effective high-throughput screening system using induced pluripotent stem cells (iPSCs). Using a Tet-On-dependent transcription factor expression system carried on the PiggyBac vector, motor neurons were efficiently and rapidly generated from iPSCs by a single-step induction method. Induced iPSC transcripts displayed characteristics similar to those of spinal cord neurons. iPSC-generated motor neurons carried a mutation in fused in sarcoma (FUS) and superoxide dismutase 1 (SOD1) genes and had abnormal protein accumulation corresponding to each mutation. Calcium imaging and multiple electrode array (MEA) recordings demonstrated that ALS neurons were abnormally hyperexcitable. Noticeably, protein accumulation and hyperexcitability were ameliorated by treatment with rapamycin (mTOR inhibitor) and retigabine (Kv7 channel activator), respectively. Furthermore, rapamycin suppressed ALS neuronal death and hyperexcitability, suggesting that protein aggregate clearance through the activation of autophagy effectively normalized activity and improved neuronal survival. Our culture system reproduced several ALS phenotypes, including protein accumulation, hyperexcitability, and neuronal death. This rapid and robust phenotypic screening system will likely facilitate the discovery of novel ALS therapeutics and stratified and personalized medicine for sporadic motor neuron diseases.

Characteristics of Extranodal NK/T-Cell Lymphoma, Nasal Type, Compared with Nasal Diffuse Large B-cell Lymphoma.

Background: Extranodal NK/T-cell lymphoma, nasal type (ENKL), is an aggressive tumour with poor prognosis. Its early diagnosis may improve the prognosis of patients; however, it is often overlooked in many cases and misdiagnosed as an inflammatory sinus disease during its initial stage. Identifying the clinical characteristics of ENKL may aid otorhinolaryngologists in indicating cases early for a pathologic examination. In this study, we aimed to investigate the clinical characteristics of ENKL compared with that of diffuse large B-cell lymphoma (DLBCL), which is the most common nasal malignant lymphoma. Methods: The backgrounds, clinical symptoms, blood test results, and computed tomography images of patients with nasal/paranasal malignant lymphoma in our hospital between 2012 and 2017 were investigated. The characteristics of ENKL and nasal DLBCL were compared to differentiate them. Results: A total of 27 patients with nasal cavity and/or paranasal sinus lymphoma were included. Extranodal NK/T-cell lymphoma, nasal type, was diagnosed in 10 patients, while DLBCL was diagnosed in 17 patients. The median age of patients with ENKL was significantly lower than that of patients with DLBCL. All patients with ENKL had a unilateral lesion in the nasal cavity, with most located at the inferior turbinate. They also experienced nasal symptoms with significantly higher incidence of nasal obstruction and tendency of bleeding. Conclusion: ENKL was often unilateral and caused nasal obstruction, unlike DLBCL. Those who are younger in age and have sinonasal tumour with unilateral nasal obstruction and bleeding should be considered for early and repeated biopsies at multiple sites, with ENKL taken into consideration.

Relationship between the severity of olfactory dysfunction and serum zinc levels.

PURPOSE: Although the association between zinc deficiency and olfactory dysfunction is inconclusive, zinc deficiency causes apoptosis of the olfactory ensheathing cells which is involved in olfactory nerve turnover and axon regeneration, thereby suggesting a possible relationship. We investigated the relationship between serum zinc levels and olfactory function in patients with olfactory dysfunction. METHODS: Ninety patients who had been diagnosed with post-infectious, posttraumatic, drug-induced, neurological and idiopathic olfactory dysfunction were included. Patients were divided into zinc normal group and zinc deficiency groups according to three reference values for serum zinc levels (60, 65, 70 µg/dL). The results of olfactory tests and patient backgrounds were used to compare the differences between the two groups. RESULTS: There were significantly worse detection and recognition thresholds in the T&T olfactometer and Open Essence (odor identification test) results in the zinc deficiency group (< 60 µg/dL). In addition, significant correlations between olfactory tests (detection/recognition thresholds in the T&T olfactometer and Open Essence results) and serum zinc levels < 65 µg/dL were observed. The zinc deficiency group < 70 µg/dL with idiopathic olfactory dysfunction had significantly worse olfactory tests (detection/recognition thresholds in the T&T olfactometer and Open Essence). In addition, there was a significant correlation between the detection/recognition thresholds in the T&T olfactometer and serum zinc levels in idiopathic olfactory dysfunction. CONCLUSIONS: Our findings suggest that zinc deficiency may exacerbate the severity of olfactory dysfunction. Furthermore, idiopathic olfactory dysfunction may be partly caused by zinc deficiency.

Symmetry-breaking host-guest assembly in a hydrogen-bonded supramolecular system.

Bio-inspired self-assembly is invaluable to create well-defined giant structures from small molecular units. Owing to a large entropy loss in the self-assembly process, highly symmetric structures are typically obtained as thermodynamic products while formation of low symmetric assemblies is still challenging. In this study, we report the symmetry-breaking self-assembly of a defined C1-symmetric supramolecular structure from an Oh-symmetric hydrogen-bonded resorcin[4]arene capsule and C2-symmetric cationic bis-cyclometalated Ir complexes, carrying sterically demanding tertiary butyl (tBu) groups, on the basis of synergistic effects of weak binding forces. The flexible capsule framework shows a large structural change upon guest binding to form a distorted resorcin[4]arene hexameric capsule, providing an asymmetric cavity. Location of the chiral guest inside the anisotropic environment leads to modulation of its Electric Dipole (ED) and Magnetic Dipole (MD) transition moments in the excited state, causing an increased emission quantum yield, longer emission lifetime, and enhancement of the dissymmetry factor (glum) in the circularly polarized luminescence.

Mirogabalin for Central Neuropathic Pain After Spinal Cord Injury: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study in Asia.

BACKGROUND AND OBJECTIVES: Patients with spinal cord injury (SCI) commonly experience central neuropathic pain (CNeP), which is challenging to treat. Mirogabalin is effective for peripheral neuropathic pain, but evidence for CNeP is lacking. METHODS: This randomized, double-blind, placebo-controlled, phase 3 study investigated mirogabalin efficacy and safety for the treatment of CNeP in patients with traumatic SCI. Adult patients from 120 sites throughout Japan, Korea, and Taiwan were randomized (1:1) to receive placebo or mirogabalin (5 mg twice daily [BID] for 1 week, 10 mg BID for 1 week, and 10 or 15 mg BID for 12 weeks). Patients with moderate renal impairment received half the dosage. The primary efficacy endpoint was change from baseline in the weekly average daily pain score (ADPS) at week 14. The secondary endpoints included ADPS responder rates, the Short-Form McGill Pain Questionnaire (SF-MPQ), average daily sleep interference score (ADSIS), and Neuropathic Pain Symptom Inventory (NPSI). Adverse events were monitored for safety. RESULTS: Each treatment group comprised 150 patients. Mirogabalin elicited a statistical and clinically relevant improvement in change from baseline in the weekly ADPS at week 14 (least-squares mean difference [95% CI] vs placebo -0.71 [-1.08 to -0.34], p = 0.0001). Responder rates at week 14 were higher for mirogabalin than those for placebo (odds ratio [95% CI] 1.91 [1.11-3.27] for the ≥30% responder rate; 2.52 [1.11-5.71] for the ≥50% responder rate). Statistical improvements (i.e., least-squares mean difference [95% CI] vs placebo) were also observed in the SF-MPQ (-2.4 [-3.8 to -1.1]), ADSIS -0.71 (-1.04 to -0.38), and NPSI -7.7 (-11.1 to -4.4) scores. Most treatment-emergent adverse events were mild; no serious adverse drug reactions were reported. DISCUSSION: Mirogabalin elicited clinically relevant decreases in pain and was well tolerated, suggesting that mirogabalin is a promising treatment for patients with CNeP due to SCI. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov (NCT03901352); first submitted April 3, 2019; first patient enrolled March 14, 2019; available at clinicaltrials.gov/ct2/show/NCT03901352. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in adult patients with CNeP due to traumatic SCI, mirogabalin, 10 or 15 mg BID, effectively improves weekly ADPS at week 14.

Evidence for the spread of SARS-CoV-2 and olfactory cell lineage impairment in close-contact infection Syrian hamster models.

Objectives: Close contact with patients with COVID-19 is speculated to be the most common cause of viral transmission, but the pathogenesis of COVID-19 by close contact remains to be elucidated. In addition, despite olfactory impairment being a unique complication of COVID-19, the impact of SARS-CoV-2 on the olfactory cell lineage has not been fully validated. This study aimed to elucidate close-contact viral transmission to the nose and lungs and to investigate the temporal damage in the olfactory receptor neuron (ORN) lineage caused by SARS-CoV-2. Methods: Syrian hamsters were orally administered SARS-CoV-2 nonvariant nCoV-19/JPN/TY/WK521/2020 as direct-infection models. On day 3 after inoculation, infected and uninfected hamsters were housed in the same cage for 30 minutes. These uninfected hamsters were subsequently assigned to a close-contact group. First, viral presence in the nose and lungs was verified in the infection and close-contact groups at several time points. Next, the impacts on the olfactory epithelium, including olfactory progenitors, immature ORNs, and mature ORNs were examined histologically. Then, the viral transmission status and chronological changes in tissue damage were compared between the direct-infection and close-contact groups. Results: In the close-contact group, viral presence could not be detected in both the nose and lungs on day 3, and the virus was identified in both tissues on day 7. In the direct-infection group, the viral load was highest in the nose and lungs on day 3, decreased on day 7, and was no longer detectable on day 14. Histologically, in the direct-infection group, mature ORNs were most depleted on day 3 (p <0.001) and showed a recovery trend on day 14, with similar trends for olfactory progenitors and immature ORNs. In the close-contact group, there was no obvious tissue damage on day 3, but on day 7, the number of all ORN lineage cells significantly decreased (p <0.001). Conclusion: SARS-CoV-2 was transmitted even after brief contact and subsequent olfactory epithelium and lung damage occurred more than 3 days after the trigger of infection. The present study also indicated that SARS-CoV-2 damages all ORN lineage cells, but this damage can begin to recover approximately 14 days post infection.

Two new species of mealybugs (Hemiptera: Coccomorpha: Pseudococcidae) from Japan.

Two new mealybug species (Hemiptera: Coccomorpha: Pseudococcidae), namely, Dysmicoccus kunaw Tanaka sp. nov. and Phenacoccus miruku Tanaka Choi sp. nov., collected in Japan, are described based on the morphological characteristics of the adult females. Dysmicoccus kunaw resembles D. trispinosus (Hall 1923) and D. furcillosus Williams 2004, but differs from them in having two conical cerarian setae in each anal lobe cerarius, a considerable number of dorsal multilocular pores on the abdominal segments, and two types of oral collar tubular ducts on the venter. Phenacoccus miruku is similar to P. sisymbriifolium Granara de Willink 2007 and P. similis Granara de Willink 1983, but differs by lacking quinqelocular pores anterior to the mouthparts and translucent pores on the hind tibiae, and in the shape of the circulus. A molecular phylogenetic analysis was used to investigate the phylogenetic placements of the two new species. Keys to the species of Dysmicoccus Ferris and Phenacoccus Cockerell found in Japan are provided.

A taxonomic study of three mealybug species (Hemiptera: Coccomorpha: Pseudococcidae) infesting dwarf bamboo in Japan, with description of a new species.

The taxonomic status of some mealybug species (Hemiptera: Coccomorpha: Pseudococcidae) found on dwarf bamboos in Japan are reviewed. A species currently placed as a junior synonym of Paraputo angustus (Ezzat McConnell 1956) was found to differ from P. angustus by having dorsal oral collar tubular ducts of two sizes rather than one, so it is revived as Formicococcus bambusiphilus (Takahashi 1958) stat. rev. and comb. nov.; it is redescribed, based on the lectotype and a paralectotype designated in this study and additional adult females collected more recently. A new species, Formicococcus kawaii sp. nov., is described; it is similar to F. bambusiphilus and Paraputo angustus (Ezzat McConnell 1956) but differs from them in having 18 pairs of cerarii, relatively large antennae and hind legs, and a dumbbell-shaped circulus. The characterization of a third dwarf bamboo-feeding species, Paraputo kaiensis (Kanda 1932), is updated based on adult females collected by the original describer and material collected more recently. Paraputo kaiensis resembles P. pauper (Danzig 1971) but differs in lacking translucent pores on the hind legs and in possessing a circulus. It also differs from most species of Paraputo Laing by having the anal opening situated on the posterior margin of the dorsum and an elongate-oval body, so the generic placement of this species remains questionable. Identification keys to separate mealybug genera with anal lobe bars and without oral rim ducts found in Asia, and to species of adult female Formicococcus in Japan and Paraputo in East Asia are provided.

Resilience of native ant community against invasion of exotic ants after anthropogenic disturbances of forest habitats.

The positive association between disturbances and biological invasions is a widely observed ecological pattern in the Anthropocene. Such patterns have been hypothesized to be driven by the superior competitive ability of invaders or by modified environments, as well as by the interaction of these factors. An experimental study that tests these hypotheses is usually less feasible, especially in protected nature areas. An alternative approach is to focus on community resilience over time after the anthropogenic disturbance of habitats. Here, we focused on ant communities within a forest to examine their responses after disturbance over time. We selected the Yanbaru region of northern Okinawa Island, which is a biodiversity hotspot in East Asia. We compared ant communities among roadside environments in forests where the road age differed from 5 to 25 years. We also monitored the ant communities before and after disturbance from forest thinning. We found that the species richness and abundance of exotic ants were higher in recently disturbed environments (roadsides of 5-15 years old roads), where the physical environment was warmer and drier. In contrast, the roadsides of 25-year-old roads indicated the potential recovery of the physical environment with cooler and moister conditions, likely owing to regrowth of roadside vegetation. At these sites, there were few exotic ants, except for those immediately adjacent to the road. The population density of the invasive species Technoymex brunneus substantially increased 1-2 years after forest thinning. There was no evidence of the exclusion of native ants by exotic ants that were recorded after disturbance. Our results suggest that local ant communities in the Yanbaru forests have some resilience to disturbance. We suggest that restoration of environmental components is a better strategy for maintaining native ant communities, rather than removing exotic ants after anthropogenic disturbance.

The identities of Pulvinaria camelicola Signoret 1873, stat. nov., and the related species,nbsp;Pulvinaria flocciferanbsp;(Westwood 1870) (Hemiptera: Coccidae) in Japan.

The soft scale, Pulvinaria floccifera (Westwood 1870) (Hemiptera: Coccidae) is a well-known agricultural and horticultural plant pest; however, there is some confusion surrounding its true taxonomic identity. The type specimens of P. floccifera differ morphologically from specimens described under this name in several recent studies. This confusion has arisen because the original description is too brief, and subsequent redescriptions were based on non-conspecific material. This taxonomically problematic situation has led to further confusion regarding the identity of P. floccifera. Herein, the oldest junior synonym of P. floccifera, i.e., Pulvinaria camelicola Signoret 1873 stat. rev., is revived to confer taxonomic stability to P. floccifera. The revived name, P. camelicola, is applied to a distinct species hitherto misidentified as P. floccifera. Morphological details of the adult female of P. camelicola stat. rev. are updated; and the adult female of P. floccifera is redescribed, based on specimens collected in Japan and some type specimens. A lectotype of P. floccifera are designated to stabilise the species identity. A key to the species of Pulvinaria found in Japan, and a table of diagnostic morphological character states of P. floccifera, P. camelicola stat. rev. and the type species of the genus, P. vitis (Linnaeus 1758), are provided to facilitate further taxonomic revision of the genus in the future.

Review of the genus Crisicoccus Ferris (Hemiptera: Coccomorpha: Pseudococcidae) in Japan with description of a new species, and the identity of a South Korean mealybug misidentified as Crisicoccus matsumotoi (Shiraiwa 1935).

Mealybug species found in Japan belonging to the genus Crisicoccus Ferris (Hemiptera: Coccomorpha: Pseudococcidae) are reviewed and the adult female of each valid species is described or update described and illustrated. Crisicoccus seruratus (Kanda 1933) and C. matsumotoi (Shiraiwa 1935) are found to be the same species, and are synonymized. A neotype is designated for C. seruratus for the purpose of taxonomic stability. A species from Japan previously identified by Ezzat & McConnell (1956) as C. matsumotoi is found to differ from specimens of C. matsumotoi from Japan and is described as a new species, Crisicoccus ezzati sp. nov. Other Crisicoccus species recorded from Japan (C. azaleae (Tinsley 1898) and C. pini (Kuwana 1902)) are characterized based on recently collected specimens. A species in South Korea that was misidentified as C. matsumotoi for over 40 years is identified as Spilococcus pacificus (Borchsenius 1949) and an updated description and an illustration of the adult female are provided. Identification keys to relevant genera and to adult females of species of Crisicoccus in Japan and Spilococcus Ferris in South Korea are provided.

Redescriptions of six Japanese species of the genus Pulvinaria (Hemiptera: Coccomorpha: Coccidae) with four new synonymies.

Six Japanese species of the genus Pulvinaria Targioni Tozzetti (Hemiptera: Coccomorpha; Coccidae): P. aurantii Cockerell, 1896, P. hazeae Kuwana, 1902, P. idesiae Kuwana, 1914, P. kuwacola Kuwana, 1907, P. nipponica Lindinger, 1933 and P. photiniae Kuwana, 1914, are redescribed and illustrated based on type specimens and some newly collected adult females. In addition, Pulvinaria decorata Borchsenius, 1957 syn. nov. and P. ornata Froggatt, 1921 (nec Hempel, 1912) syn. nov. are proposed as new junior synonyms of P. aurantii, and Pulvinaria fujisana Kanda, 1960 syn. nov. and P. hydrangeae Steinweden, 1946 syn. nov. are proposed as new junior synonyms of P. kuwacola. Lectotypes are designated for P. idesiae, P. nipponica and P. photiniae from the syntypes of these species and, in the absence of any original material, neotypes are designated for P. hazeae and P. kuwacola, respectively, using specimens collected from the type localities. To facilitate comparisons, a table containing diagnostic morphological character states of the redescribed species and the type species of the genus, P. vitis (Linnaeus, 1758), is provided.

A parasitic insect on a parasitic plant: a new species of the genus Formicoccus Takahashi (Hemiptera, Coccomorpha, Pseudococcidae) from Ishigaki Island, Japan.

A new species of the genus Formicoccus Takahashi (Hemiptera, Coccomorpha, Pseudococcidae) collected from the holoparasitic plant Balanophorafungosa J. R. & G. Forst (Balanophoraceae), on Ishigaki Island, Japan, is described as Formicoccusyoshinoi Tanaka, sp. nov. based on the morphology of adult females. This species is similar to F.formicarius (1900) and F.erythrinae Williams, 2004, but differs from them by having fewer than six cerarii, and only one type of ventral oral collar tubular duct distributed on the medial area of the posterior abdominal segments. Keys to the Oriental species of the genus Formicoccus are provided.

Novel Platform for Predicting Drug Effects in Patients with Acromegaly: Translational Exposure-Response Evaluation of Growth Hormone-Inhibitory Effect of Octreotide after Growth Hormone-Releasing Hormone Stimulation.

Acromegaly is a chronic systemic disease characterized by facial and peripheral changes caused by soft tissue overgrowth and is associated with multiple comorbidities. Despite available surgical and medical therapies, suitable treatments for acromegaly are still lacking. Efficient drug development requires an understanding of the exposure-response (E-R) relationship based on nonclinical and early clinical studies. We aimed to establish a platform to facilitate the development of novel drugs to treat acromegaly. We evaluated the E-R relationship of the growth hormone (GH)-inhibitory effect of the somatostatin analog octreotide under growth hormone-releasing hormone + arginine stimulation in healthy participants and compared the results with historical data for patients with acromegaly. This randomized five-way crossover study included two placebo and three active-treatment periods with different doses of octreotide acetate. GH secretion in the two placebo periods was comparable, which confirmed the reproducibility of the response with no carryover effect. GH secretion was inhibited by low-, medium-, and high-dose octreotide acetate in a dose-dependent manner. We also examined the E-R relationship in monkeys as a preclinical drug evaluation study and in rats as a more convenient and simple system for screening candidate drugs. The E-R relationships and EC50 values were similar among animals, healthy participants, and patients with acromegaly, which suggests that GH stimulation studies in early research and development allowed simulation of the drug response in patients with acromegaly. SIGNIFICANCE STATEMENT: This study demonstrated similar exposure-response relationships in terms of the growth hormone-inhibitory effect of octreotide after growth hormone-releasing hormone stimulation among healthy participants, monkeys, and rats. The research methods and analyses utilized in this study will be useful for simulating the dosages and therapeutic effects of drugs for acromegaly and will facilitate the research and development of novel therapeutic agents with similar modes of action.