Comprehensive analysis of immune responses in CLL patients after heterologous COVID-19 vaccination

Patients with chronic lymphocytic leukemia (CLL) treated with B-cell pathway inhibitors and anti-CD20 antibodies exhibit low humoral response rate (RR) following SARS-CoV-2 vaccination. To investigate the relationship between the initial transcriptional response to vaccination with ensuing B and T cell immune responses, we performed a comprehensive immune transcriptome analysis flanked by antibody and T cell assays in peripheral blood prospectively collected from 15 CLL/SLL patients vaccinated with heterologous BNT162b2/ChAdOx1 with follow up at a single institution. The two-dose antibody RR was 40% increasing to 53% after booster. Patients on BTKi, venetoclax {+/-} anti-CD20 antibody within 12 months of vaccination responded less well than those under BTKi alone. The two-dose T cell RR was 80% increasing to 93% after booster. Transcriptome studies revealed that seven patients showed interferon-mediated signaling activation within 2 days and one at 7 days after vaccination. Increasing counts of COVID-19 specific IGHV genes correlated with B-cell reconstitution and improved humoral RR. T cell responses in CLL patients appeared after vaccination regardless of treatment status. A higher humoral RR was associated with BTKi treatment and B-cell reconstitution. Boosting was particularly effective when intrinsic immune status was improved by CLL-treatment.

Genetic immune response and antibody repertoire of heterologous ChAdOx1-BNT162b2 vaccination in a Korean cohort

Heterologous ChAdOx1-BNT162b2 vaccination induces a stronger immune response than two doses of BNT162b2 or ChAdOx1. Yet, the molecular transcriptome, the germline allelic variants of immunoglobulin loci and anti-Omicron antibody levels induced by the heterologous vaccination have not been formally investigated. Moreover, there is a paucity of COVID vaccine studies including diverse genetic populations. Here, we show a robust molecular immune transcriptome and antibody repertoire in 51 office workers from the Republic of Korea after a heterologous ChAdOx1-BNT162b2 vaccination or a homologous ChAdOx1-ChAdOx1 vaccination. Anti-spike-specific IgG antibody levels in the heterologous group increased from 14,000 U/ml to 142,000 AU/ml within eight days after the BNT162b2 vaccination. In contrast, antibody levels in the homologous group increased two-fold after the second ChAdOx1 dose. Antibody titers against the Omicron spike protein as compared to the ancestral strain were reduced to a lesser extent in the heterologous group. RNA-seq conducted on immune cells demonstrated a stronger activation of interferon-induced genetic programs in the heterologous cohort. An increase of specific IGHV clonal transcripts encoding neutralizing antibodies was preferentially detected in the heterologous cohort. Enrichment of B cell and CD4+ T cell responses were observed following both heterologous and homologous vaccination using scRNA-seq, but clonally expanded memory B cells were relatively stronger in the ChAdOx1-BNT162b2 cohort. In summary, a heterologous vaccination with ChAdOx1 followed by BNT162b2 provides an innate and adaptive immune response exceeding that seen in homologous ChAdOx1 vaccinations but equivalent to that seen in homologous BNT162b2 vaccination.

Effect of corticosteroid therapy in the early phase of acute respiratory distress syndrome: a propensitymatched cohort study

Background/Aims@#It is unclear whether corticosteroid use in patients with acute respiratory distress syndrome (ARDS) improves survival. This study aimed to investigate whether the administration of corticosteroids to patients in the early phase of moderate to severe ARDS is associated with improved outcomes. @*Methods@#We analyzed the data of patients who received corticosteroids within 7 days of the onset of ARDS between June 2006 and December 2015 at a single tertiary teaching hospital. A total of 565 patients admitted with moderate to severe ARDS were eligible. The outcomes of patients treated with methylprednisolone 40 to 180 mg/day or equivalent (n = 404) were compared to those who did not receive steroids (n = 161). The primary and secondary outcomes were 28- and 90-day mortality rates, respectively. Propensity scores were used to adjust for baseline covariates. @*Results@#The overall mortality at 28 days was not significantly different between the corticosteroid-treated and control groups (43.8% vs. 41%, p = 0.541). At 90 days, the overall mortality rate was higher in the corticosteroid-treated group than in the control group (59.2% vs. 48.4%, p = 0.021). However, on propensity score matching, corticosteroid therapy was not associated with a higher 28-day mortality rate (odds ratio, 1.031; 95% confidence interval, 0.657 to 1.618; p = 0.895) and 90 days (odds ratio, 1.435; 95% confidence interval, 0.877 to 2.348; p = 0.151). @*Conclusions@#Corticosteroid therapy was not associated with 28- or 90-day mortality in the early phase of moderate to severe ARDS on propensity score matching analysis.

Comparison of rivaroxaban and dalteparin for the long-term treatment of venous thromboembolism in patients with gynecologic cancers / 부인종양

Synaptic loss and amyloid beta alterations in the rodent hippocampus induced by streptozotocin injection into the cisterna magna / 한국실험동물학회지

To date, researchers have developed various animal models of Alzheimer’s disease (AD) to investigate its mechanisms and to identify potential therapeutic treatments. A widely recognized model that mimics the pathology of human sporadic AD involves intracerebroventricular (ICV) injection with streptozotocin (STZ). However, ICV injections are an invasive approach, which creates limitations in generalizing the results. In this study, we produced a rodent model of AD using STZ (3 mg/kg) injection via the cisterna magna (CM) once every week for 4 weeks, and analyzed at 4 weeks and 16 weeks after final injection. In the CM-STZ rodent model of AD, we observed increase in extracellular amyloid-beta (Aβ) deposition and decrease and abnormal morphology of post-synaptic protein, PSD95 in 16 weeks STZ-injected group. The model developed using our less-invasive method induced features of AD-like pathology, including significantly increased extracellular amyloid-beta deposition, and decreased synaptic protein in the hippocampus. These findings supporting the success of this alternative approach, and thus, we suggest this is a promising, less invasive model for use in future AD research.

Comparison of rivaroxaban and dalteparin for the long-term treatment of venous thromboembolism in patients with gynecologic cancers / 부인종양

Objectives@#Two randomized, controlled studies comparing outcomes in patients treated with direct oral anticoagulants or low-molecular weight heparin for cancer-associated venous thromboembolism (VTE) have previously been performed. However, gynecologic cancers accounted for approximately 10% of the study populations. We compared the outcomes of patients with primary gynecological cancers who were treated for cancer-associated VTE with either rivaroxaban or dalteparin. @*Methods@#The 162 eligible patients with gynecologic cancers who were treated with either dalteparin (n=60) or rivaroxaban (n=102) were reviewed. The primary outcome was a composite event, which included recurrence or clinically relevant bleeding events during the therapeutic period. Secondary outcomes were recurrence, clinically relevant bleeding events, and mortality. @*Results@#During the therapeutic period, there were no significant differences between the groups in the proportion of composite events, recurrence, or clinically relevant bleeding. Multivariate analysis using the Cox proportional hazards model also showed no significant difference in the number of composite events and clinically relevant bleeding between the groups. In the rivaroxaban group, 44.0% of patients experienced gastrointestinal bleeding and 24.0% experienced urinary tract bleeding. In the dalteparin group, bleeding was most common in the urinary tract (44.4%) and at the injection site (22.2%). @*Conclusion@#In this study, although there were no significant differences in effectiveness or safety between the rivaroxaban and dalteparin groups, rivaroxaban use was associated with a higher rate of clinically relevant bleeding than dalteparin. Therefore, caution should be taken when prescribing rivaroxaban for gynecologic cancer-associated VTE and bleeding events should be carefully monitored.

Impaired Hand Dexterity Function in a Non-human Primate Model with Chronic Parkinson’s Disease

ymptoms of Parkinson’s disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed the alteration in Parkinsonian tremor signs and the functionality of presynaptic dopaminergic neuron using positron emission tomography imaging of dopamine transporters in these models. In addition, a significant inverse correlation between HDT and DAT level was identified, but no local bias was found. The correlation with intention tremor signs was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.

Assessment of Hand Motor Function in a Non-human Primate Model of Ischemic Stroke

Ischemic stroke results from arterial occlusion and can cause irreversible brain injury. A non-human primate (NHP) model of ischemic stroke was previously developed to investigate its pathophysiology and for efficacy testing of therapeutic candidates; however, fine motor impairment remains to be well-characterized. We evaluated hand motor function in a cynomolgus monkey model of ischemic stroke. Endovascular transient middle cerebral artery occlusion (MCAO) with an angiographic microcatheter induced cerebral infarction. In vivo magnetic resonance imaging mapped and measured the ischemia-induced infarct lesion. In vivo diffusion tensor imaging (DTI) of the stroke lesion to assess the neuroplastic changes and fiber tractography demonstrated three-dimensional patterns in the corticospinal tract 12 weeks after MCAO. The hand dexterity task (HDT) was used to evaluate fine motor movement of upper extremity digits. The HDT was modified for a home cage-based training system, instead of conventional chair restraint training. The lesion was localized in the middle cerebral artery territory, including the sensorimotor cortex. Maximum infarct volume was exhibited over the first week after MCAO, which progressively inhibited ischemic core expansion, manifested by enhanced functional recovery of the affected hand over 12 weeks after MCAO. The total performance time decreased with increasing success rate for both hands on the HDT. Compensatory strategies and retrieval failure improved in the chronic phase after stroke. Our findings demonstrate the recovery of fine motor skill after stroke, and outline the behavioral characteristics and features of functional disorder of NHP stroke model, providing a basis for assessing hand motor function after stroke.

Derivation and validation of modified early warning score plus SpO2/FiO2 score for predicting acute deterioration of patients with hematological malignancies

Background/Aims@#Scoring systems play an important role in predicting intensive care unit (ICU) admission or estimating the risk of death in critically ill patients with hematological malignancies. We evaluated the modified early warning score (MEWS) for predicting ICU admissions and in-hospital mortality among at-risk patients with hematological malignancies and developed an optimized MEWS. @*Methods@#We retrospectively analyzed derivation cohort patients with hematological malignancies who were managed by a medical emergency team (MET) in the general ward and prospectively validated the data. We compared the traditional MEWS with the MEWS plus SpO2/FiO2 (MEWS_SF) score, which were calculated at the time of MET contact. @*Results@#In the derivation cohort, the areas under the receiver-operating characteristic (AUROC) curves were 0.81 for the MEWS (95% confidence interval [CI], 0.76 to 0.87) and 0.87 for the MEWS_SF score (95% CI, 0.87 to 0.92) for predicting ICU admission. The AUROC curves were 0.70 for the MEWS (95% CI, 0.63 to 0.77) and 0.76 for the MEWS_SF score (95% CI, 0.70 to 0.83) for predicting in-hospital mortality. In the validation cohort, the AUROC curves were 0.71 for the MEWS (95% CI, 0.66 to 0.77) and 0.83 for the MEWS_SF score (95% CI, 0.78 to 0.87) for predicting ICU admission. The AUROC curves were 0.64 for the MEWS (95% CI, 0.57 to 0.70) and 0.74 for the MEWS_SF score (95% CI, 0.69 to 0.80) for predicting in-hospital mortality. @*Conclusions@#Compared to the traditional MEWS, the MEWS_SF score may be a useful tool that can be used in the general ward to identify deteriorating patients with hematological malignancies.

The quick sepsis-related organ failure score has limited value for predicting adverse outcomes in sepsis patients with liver cirrhosis

Background/Aims@#The quick Sepsis-related Organ Failure Assessment (qSOFA) is a newly developed risk stratification tool, which has been presented along with a new sepsis definition, to classify infected patients outside of the intensive care unit (ICU). We evaluated the clinical usefulness of qSOFA for predicting adverse outcomes in sepsis patients with liver cirrhosis. @*Methods@#We performed a retrospective cohort study to assess the utility of qSOFA in sepsis patients with liver cirrhosis for whom medical emergency teams (METs) were activated in general wards at an academic tertiary care hospital between March 2008 and December 2015. qSOFA, Systemic inflammatory response syndrome (SIRS), modified early warning score (MEWS), and sequential (sepsis- related) organ failure assessment (SOFA) scores were calculated according to data at MET activation. @*Results@#Of 188 patients, 69 (36.7%) had a qSOFA score of 0 or 1 point and 119 (63.3%) had ≥ 2 points. The areas under the receiver operating characteristic curve (AUROC) for ICU transfer on the SOFA (AUROC, 0.691; 95% confidence interval [CI], 0.615 to 0.767) or MEWS (AUROC, 0.663; 95% CI, 0.586 to 0.739) were significantly higher compared to those for qSOFA (AUROC, 0.589; 95% CI, 0.507 to 0.671) or SIRS (AUROC, 0.533; 95% CI, 0.451 to 0.616). @*Conclusions@#Our findings suggest that qSOFA score may have limited utility in predicting adverse outcomes in sepsis patients with liver cirrhosis at MET activation. Either MEWS or another screening tool is needed for detecting early sepsis in these patients.

Association between clinical risk factors and severity of dysphagia after extubation based on a videofluoroscopic swallowing study

Background/Aims@#This study aimed to evaluate the correlation between clinical risk factors of post-extubation dysphagia (PED) and the severity of impaired pharyngeal swallowing function assessed via videofluoroscopic swallowing studies (VFSSs). @*Methods@#This study was a retrospective review of medical records. Of 116 patients who were admitted to the intensive care unit and underwent VFSS, 32 who had non-neurologic disorders and experienced prolonged intubation (for more than 48 hours) were diagnosed with PED. The severity of PED was evaluated by using a functional dysphagia scale (FDS) and a penetration aspiration scale (PAS), on the basis of VFSS. @*Results@#The Simplified Acute Physiology Score 3 and total FDS score were positively correlated (r = 0.40, p = 0.02). Intubation duration was positively correlated with total PAS and FDS scores (r = 0.62, p < 0.001; r = 0.65, p < 0.001, respectively). The amounts of residue in the valleculae (RV) and pyriform sinuses (RP) were associated with intubation duration (r = 0.58, p < 0.001; r = 0.57, p < 0.001, respectively). Multivariate regression analysis revealed that intubation duration was significantly associated with the total FDS score, RV and RP subscales of the FDS, and total PAS score. @*Conclusions@#The severity of impaired swallowing function, particularly the amount of residue in the pharyngeal recesses assessed via VFSS, was strongly associated with both severity of medical illness and intubation duration. Intubation duration could be a prognostic factor for assessing impaired swallowing function on the basis of VFSS.

Iatrogenic Opioid Withdrawal Syndrome in Critically Ill Patients: a Retrospective Cohort Study

Background@#Opioid withdrawal syndrome (OWS) may occur following the reduction or discontinuation of opioid analgesics. In critically ill pediatric patients, OWS is a common and clinically significant condition. However, OWS in adult patients has not been assessed in detail. Therefore, we aimed to investigate the incidence, risk factors, and clinical features of OWS in mechanically ventilated patients treated in an adult intensive care unit (ICU). @*Methods@#This study was a retrospective evaluation of data from patients treated in the medical ICU for > 3 days and who received only one type of opioid analgesic. OWS was assessed over a 24 hours period from discontinuation or reduction (by > 50%) of continuous opioid infusion. OWS was defined as the presence of ≥ 3 central nervous system or autonomic nervous system symptoms. @*Results@#In 126 patients treated with remifentanil (n = 58), fentanyl (n = 47), or morphine (n = 21), OWS was seen in 31.0%, 36.2%, and 9.5% of patients, respectively (P = 0.078). The most common symptom was a change in respiratory rate (remifentanil, 94.4%; fentanyl, 76.5%; morphine, 100%). Multivariate Cox-proportional hazards model showed that OWS was negatively associated with morphine treatment (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.037–0.743) and duration of opioid infusion (HR, 0.566; 95% CI, 0.451–0.712). @*Conclusion@#OWS is not uncommon in mechanically ventilated adult patients who received continuous infusion of opioids for > 3 days. The use of morphine may be associated with a decreased risk of OWS.

Safety of antimicrobial de-escalation for culture-negative severe pneumonia.

PURPOSE: This study investigated the outcomes of antimicrobial de-escalation (ADE) based on mortality and the incidence of multi-drug resistant (MDR) pathogen occurrence in patients with culture-negative pneumonia presenting with sepsis and septic shock. MATERIALS AND METHODS: We retrospectively analyzed patients diagnosed with severe pneumonia requiring intensive care unit (ICU) admission and possessing negative microbiological culture results at a tertiary referral hospital in South Korea from March 2008 to July 2018. RESULTS: We identified 107 patients with culture-negative pneumonia. The Acute Physiologic and Chronic Health Evaluation (APACHE) II and Sepsis-related Organ Failure Assessment (SOFA) mean scores were 20.3 ±â€¯8.6 and 9.6 ±â€¯3.3, respectively. Among the patients, 40 (37.4%) underwent ADE. The APACHE II, SOFA, and follow-up SOFA scores did not differ significantly between the groups, and no differences were found in ICU mortality and MDR pathogen occurrence (27.5% vs 41.8%, P = .137 and 15.0% vs 16.9% P = .794, respectively). CONCLUSIONS: We observed similar ICU mortality and MDR pathogen occurrence in patients with culture-negative pneumonia presenting with sepsis/shock regardless of whether they received ADE. Additionally, ADE lowered the antimicrobial burden.

Erratum: Effect of vitamin D deficiency in Korean patients with acute respiratory distress syndrome

There is a spelling mistake of an author's name, and the authors want to change to Min Gee Lee from Min Gi Lee.

Reference values of hematological and biochemical parameters in young-adult cynomolgus monkey (Macaca fascicularis) and rhesus monkey (Macaca mulatta) anesthetized with ketamine hydrochloride / 한국실험동물학회지

Nonhuman primate models are valuable in biomedical research. However, reference data for clinical pathology parameters in cynomolgus and rhesus monkeys are limited. In the present study, we established hematologic and biochemical reference intervals for healthy cynomolgus and rhesus monkeys anesthetized with ketamine hydrochloride. A total of 142 cynomolgus monkeys (28 males and 114 females) and 42 rhesus monkeys (22 males and 20 females) were selected and analyzed in order to examine reference intervals of 20 hematological and 16 biochemical parameters. The effects of sex were also investigated. Reference intervals for hematological and biochemical parameters were separately established by species (cynomolgus and rhesus) and sex (male and female). No sex-related differences were determined in erythrocyte-related parameters for cynomolgus and rhesus monkey housed in indoor laboratory conditions. Alkaline phosphatase and gamma glutamyltransferase were significantly lower in females than males in both cynomolgus and rhesus monkeys aged 48–96 months. The reference values for hematological and biochemical parameters established herein might provide valuable information for researchers using cynomolgus and rhesus monkeys in experimental conditions for biomedical studies.

Evaluation of fecal microbiomes associated with obesity in captive cynomolgus monkeys (Macaca fascicularis)

Microorganisms play important roles in obesity; however, the role of the gut microbiomes in obesity is controversial because of the inconsistent findings. This study investigated the gut microbiome communities in obese and lean groups of captive healthy cynomolgus monkeys reared under strict identical environmental conditions, including their diet. No significant differences in the relative abundance of Firmicutes, Bacteroidetes and Prevotella were observed between the obese and lean groups, but a significant difference in Spirochetes (p < 0.05) was noted. Microbial diversity and richness were similar, but highly variable results in microbial composition, diversity, and richness were observed in individuals, irrespective of their state of obesity. Distinct clustering between the groups was not observed by principal coordinate analysis using an unweighted pair group method. Higher sharedness values (95.81% ± 2.28% at the genus level, and 79.54% ± 5.88% at the species level) were identified among individual monkeys. This paper reports the association between the gut microbiome and obesity in captive non-human primate models reared under controlled environments. The relative proportion of Firmicutes and Bacteroidetes as well as the microbial diversity known to affect obesity were similar in the obese and lean groups of monkeys reared under identical conditions. Therefore, obesity-associated microbial changes reported previously appear to be associated directly with environmental factors, particularly diet, rather than obesity.

Comparative Evaluation of Hormones and Hormone-Like Molecule in Lineage Specification of Human Induced Pluripotent Stem Cells

BACKGROUND AND OBJECTIVES: Proficient differentiation of human pluripotent stem cells (hPSCs) into specific lineages is required for applications in regenerative medicine. A growing amount of evidences had implicated hormones and hormone-like molecules as critical regulators of proliferation and lineage specification during in vivo development. Therefore, a deeper understanding of the hormones and hormone-like molecules involved in cell fate decisions is critical for efficient and controlled differentiation of hPSCs into specific lineages. Thus, we functionally and quantitatively compared the effects of diverse hormones (estradiol 17-β (E2), progesterone (P4), and dexamethasone (DM)) and a hormone-like molecule (retinoic acid (RA)) on the regulation of hematopoietic and neural lineage specification. METHODS AND RESULTS: We used 10 nM E2, 3 μM P4, 10 nM DM, and 10 nM RA based on their functional in vivo developmental potential. The sex hormone E2 enhanced functional activity of hematopoietic progenitors compared to P4 and DM, whereas RA impaired hematopoietic differentiation. In addition, E2 increased CD34⁺CD45⁺ cells with progenitor functions, even in the CD43⁻ population, a well-known hemogenic marker. RA exhibited lineage-biased potential, preferentially committing hPSCs toward the neural lineage while restricting the hematopoietic fate decision. CONCLUSIONS: Our findings reveal unique cell fate potentials of E2 and RA treatment and provide valuable differentiation information that is essential for hPSC applications.

Increased CD68/TGFβ Co-expressing Microglia/Macrophages after Transient Middle Cerebral Artery Occlusion in Rhesus Monkeys

The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found colocalized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206⁺ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68⁺ microglia/macrophages can therefore be used as a potential therapeutic target.

Abnormal Mitochondria in a Non-human Primate Model of MPTP-induced Parkinson's Disease: Drp1 and CDK5/p25 Signaling

Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.

Rise of the Visible Monkey: Sectioned Images of Rhesus Monkey

BACKGROUND: Gross anatomy and sectional anatomy of a monkey should be known by students and researchers of veterinary medicine and medical research. However, materials to learn the anatomy of a monkey are scarce. Thus, the objective of this study was to produce a Visible Monkey data set containing cross sectional images, computed tomographs (CTs), and magnetic resonance images (MRIs) of a monkey whole body. METHODS: Before and after sacrifice, a female rhesus monkey was used for 3 Tesla MRI and CT scanning. The monkey was frozen and sectioned at 0.05 mm intervals for the head region and at 0.5 mm intervals for the rest of the body using a cryomacrotome. Each sectioned surface was photographed using a digital camera to obtain horizontal sectioned images. Segmentation of sectioned images was performed to elaborate three-dimensional (3D) models of the skin and brain. RESULTS: A total of 1,612 horizontal sectioned images of the head and 1,355 images of the remaining region were obtained. The small pixel size (0.024 mm × 0.024 mm) and real color (48 bits color) of these images enabled observations of minute structures. CONCLUSION: Due to small intervals of these images, continuous structures could be traced completely. Moreover, 3D models of the skin and brain could be used for virtual dissections. Sectioned images of this study will enhance the understanding of monkey anatomy and foster further studies. These images will be provided to any requesting researcher free of charge.