An evaluation of rehabilitation students' learning goals in their first year: a text mining approach.

Introduction: Qualitative information in the form of written reflection reports is vital for evaluating students' progress in education. As a pilot study, we used text mining, which analyzes qualitative information with quantitative features, to investigate how rehabilitation students' goals change during their first year at university. Methods: We recruited 109 first-year students (66 physical therapy and 43 occupational therapy students) enrolled in a university rehabilitation course. These students completed an open-ended questionnaire about their learning goals at the time of admission and at 6 and 12 months after admission to the university. Text mining was used to objectively interpret the descriptive text data from all three-time points to extract frequently occurring nouns at once. Then, hierarchical cluster analysis was performed to generate clusters. The number of students who mentioned at least one noun in each cluster was counted and the percentages of students in each cluster were compared for the three periods using Cochran's Q test. Results: The 31 nouns that appeared 10 or more times in the 427 sentences were classified into three clusters: "Socializing," "Practical Training," and "Classroom Learning." The percentage of students in all three clusters showed significant differences across the time periods (p < 0.001 for "Socializing"; p < 0.01 for "Practical Training" and "Classroom Learning"). Conclusion: These findings suggest that the students' learning goals changed during their first year of education. This objective analytical method will enable researchers to examine transitional trends in students' reflections and capture their psychological changes, making it a useful tool in educational research.

Morphological characteristics of SETD2-mutated locally advanced clear cell renal cell carcinoma: Comparison with BAP1-mutated clear cell renal cell carcinoma.

SET-domain containing 2 (SETD2) and BRCA1-associated protein 1 (BAP1), both chromatin remodeling genes, are frequently mutated in clear cell renal cell carcinoma (ccRCC) and involved in tumor progression and metastasis. Herein, we studied clinicopathologic features of 7 cases of locally advanced ccRCC with single SETD2 mutation, and compared to 7 cases of locally advanced ccRCC with single BAP1 mutation. SETD2-mutated ccRCC showed high-grade transformation, comprising of enlarged tumor cells with voluminous clear cytoplasm, enlarged irregular nuclei with prominent nucleoli, eosinophilic cytoplasmic granules, arranged in various architectural patterns such as large nested, tubular, tubulopapillary and solid. 71 % (5 of 7 cases) of SETD2-mutated ccRCC showed a rhabdoid morphology. SETD2-mutated ccRCC have striking propensity for invasive growth; all cases have vascular invasion and perirenal (extracapsular) adipose tissue invasion. After nephrectomy, distant metastasis was found in 67 % (4 of 7 cases) of patients with SETD2-mutated ccRCC. The most common metastatic site was the lung (3 cases), followed by precaval lymph nodes (1 case). BAP1-mutated ccRCC also showed a similar high-grade morphology, with rhabdoid and/or sarcomatoid features. Their high-grade features mostly overlapped with those of SETD2-mutated ccRCC, which makes difficult to predict the presence of BAP1 or SETD2 mutation solely from morphology. These findings justify the use of molecular testing to detect these mutations, especially when we encounter high-grade ccRCC. Detecting SETD2 and BAP1 mutation in ccRCC is useful for risk stratification and proper therapeutic strategy.

Cell Responses of the Ventrolateral Medulla to PAR1 Activation and Changes in Respiratory Rhythm in Newborn Rat En Bloc Brainstem-Spinal Cord Preparations.

Proteinase-activated receptor-1 (PAR1) is expressed in astrocytes of various brain regions, and its activation is involved in the modulation of neuronal activity. Here, we report effects of PAR1 selective agonist TFLLR on respiratory rhythm generation in brainstem-spinal cord preparations. Preparations were isolated from newborn rats (P0-P4) under deep isoflurane anesthesia and were transversely cut at the rostral medulla. Preparations were superfused with artificial cerebrospinal fluid (25-26 °C), and inspiratory C4 ventral root activity was monitored. The responses to TFLLR of cells close to the cut surface were detected by calcium imaging or membrane potential recordings. Application of 10 µM TFLLR (4 min) induced a rapid and transient increase of calcium signal in cells of the ventrolateral respiratory regions of the medulla. More than 88% of responding cells (223/254 cells from 13 preparations) were also activated by low (0.2 mM) K+ solution, suggesting that they were astrocytes. Immunohistochemical examination demonstrated that PAR1 was expressed on many astrocytes. Respiratory-related neurons in the medulla were transiently hyperpolarized (-1.8 mV) during 10 µM TFLLR application, followed by weak membrane depolarization after washout. C4 burst rate decreased transiently in response to application of TFLLR, followed by a slight increase. The inhibitory effect was partially blocked by 50 µM theophylline. In conclusion, activation of astrocytes via PAR1 resulted in a decrease of inspiratory C4 burst rate in association with transient hyperpolarization of respiratory-related neurons. After washout, slow and weak excitatory responses appeared. Adenosine may be partially involved in the inhibitory effect of PAR1 activation.

Minocycline prevents hypoxia-induced seizures.

Severe hypoxia induces seizures, which reduces ventilation and worsens the ictal state. It is a health threat to patients, particularly those with underlying hypoxic respiratory pathologies, which may be conducive to a sudden unexpected death in epilepsy (SUDEP). Recent studies provide evidence that brain microglia are involved with both respiratory and ictal processes. Here, we investigated the hypothesis that microglia could interact with hypoxia-induced seizures. To this end, we recorded electroencephalogram (EEG) and acute ventilatory responses to hypoxia (5% O2 in N2) in conscious, spontaneously breathing adult mice. We compared control vehicle pre-treated animals with those pre-treated with minocycline, an inhibitory modulator of microglial activation. First, we histologically confirmed that hypoxia activates microglia and that pre-treatment with minocycline blocks hypoxia-induced microglial activation. Then, we analyzed the effects of minocycline pre-treatment on ventilatory responses to hypoxia by plethysmography. Minocycline alone failed to affect respiratory variables in room air or the initial respiratory augmentation in hypoxia. The comparative results showed that hypoxia caused seizures, which were accompanied by the late phase ventilatory suppression in all but one minocycline pre-treated mouse. Compared to the vehicle pre-treated, the minocycline pre-treated mice showed a delayed occurrence of seizures. Further, minocycline pre-treated mice tended to resist post-ictal respiratory arrest. These results suggest that microglia are conducive to seizure activity in severe hypoxia. Thus, inhibition of microglial activation may help suppress or prevent hypoxia-induced ictal episodes.

Post-kidney transplant cancers: Racial and ethnic differences in sun-exposed skin versus non-sun-exposed anogenital skin.

BACKGROUND: Transplant recipients have a 2- to 4-fold increased risk of developing malignancies over the general population. Cancer is the second most common cause of death for recipients. The magnitude of the risk depends on the cancer type and increases in viral-related malignancies. Skin cancer is the most common. However, data in most cancer registries is limited to cutaneous melanomas, thereby limiting the epidemiologic examination of cancer risk in non-melanoma skin cancer. Our goal was to evaluate post-kidney transplant cancer cases and sites in our population to guide screening recommendations. METHODS: Between 2009 and 2015, a retrospective study of adult kidney recipients transplanted at East Carolina University was conducted. The first cancer diagnosis after transplant through February 18, 2020, was captured and analyzed. Patient demographics, cancer sites, and histological diagnoses were analyzed and compared. p16 immunohistochemistry was used as a surrogate marker for high-risk human papillomavirus (HPV) infection. RESULTS: Retrospectively, kidney transplant recipients were analyzed (N = 439), the majority were non-Hispanic Black (NHB) individuals, 312 (71.1%), and 127 (28.9%) were non-Hispanic White (NHW) individuals. Of these, 59 (13.4%) developed a posttransplant malignancy, with the majority on sun-exposed skin found in NHW. NHB had all anogenital/mucosa skin cancers on non-sun-exposed skin. Of these detected in NHB, all were squamous cell carcinomas, with five out of six (83.3%) being positive for p16. CONCLUSIONS: Posttransplant malignancy differed significantly by race, site, and potential source of etiology. The majority of malignancies are likely explained by acceleration of precursor lesions from prior exposure to ultraviolet rays or HPV.

A new system to measure the trunk angle and pelvis angle during wheelchair propulsion.

BACKGROUND: The number of wheelchair users is increasing as the population ages. However, there is still lack of tools to objectively assess posture during wheelchair propulsion. OBJECTIVE: The purpose of this study was to develop a system to measure trunk and pelvis ROM (range of motion) while driving a wheelchair and to assess the reproducibility of the measured posture changes and cyclic fluctuations during propulsion. METHODS: Motion recorders were attached to the sternum and pelvis of fifteen healthy adults, and a pressure sensor was attached to the right heel. Subjects drove a standard wheelchair using their right leg and trunk and pelvis ROM was measured in two separate sessions. To detect the trend of postural changes during propulsion, a trend curve was computed from the measured ROM using a low-pass filter and then subtracted from the measured ROM waveforms. The resulting curves were normalized and averaged, and the maximum, minimum, and amplitude of the cyclic variation during propulsion were assessed for reproducibility. RESULTS: Intraclass correlation coefficients of the maximum, minimum, and amplitude ranged from 0.65 to 0.84. CONCLUSIONS: The proposed method can estimate the posture change and the periodic fluctuation during wheelchair propulsion with high reproducibility.

Role of microglia in blood pressure and respiratory responses to acute hypoxic exposure in rats.

Microglia modulate cardiorespiratory activities during chronic hypoxia. It has not been clarified whether microglia are involved in the cardiorespiratory responses to acute hypoxia. Here we investigated this issue by comparing cardiorespiratory responses to two levels of acute hypoxia (13% O2 for 4 min and 7% O2 for 5 min) in conscious unrestrained rats before and after systemic injection of minocycline (MINO), an inhibitor of microglia activation. MINO increased blood pressure but not lung ventilation in the control normoxic condition. Acute hypoxia stimulated cardiorespiratory responses in MINO-untreated rats. MINO failed to significantly affect the magnitude of hypoxia-induced blood pressure elevation. In contrast, MINO tended to suppress the ventilatory responses to hypoxia. We conclude that microglia differentially affect cardiorespiratory regulation depending on the level of blood oxygenation. Microglia suppressively contribute to blood pressure regulation in normoxia but help maintain ventilatory augmentation in hypoxia, which underscores the dichotomy of central regulatory pathways for both systems.

A Quantitative and Qualitative Assessment of Frozen Section Diagnosis Accuracy and Deferral Rate Across Organ Systems.

OBJECTIVES: Monitoring of frozen section diagnostic performance provides an important quality improvement measure. METHODS: Surgical specimens involving a frozen section diagnosis over a 3-year period were retrospectively reviewed. Glass slides were reviewed on cases with discordance. Discordance and deferral rates were calculated. RESULTS: Of 3,675 frozen section diagnoses included, 96 (2.7%) were discordant with the final diagnosis. Additionally, 114 frozen section diagnoses (3.1%) were deferred. The organ-specific discordance rates were lowest in breast and genitourinary specimens and highest for pancreas, lymph node, and gynecologic specimens. Deferral rates were highest in musculoskeletal, breast, and hepatobiliary cases and lowest in thyroid, parathyroid, and neuropathology cases. Discordance was explained by block-sampling error (45%), specimen-sampling error (27%), or interpretation error (27%). Discordant frozen section diagnoses from gynecologic specimens were responsible for 81% of specimen-sampling errors; frozen section diagnoses of lymph nodes, head and neck, and pancreas were responsible for 54% of interpretation errors; 51% of block-sampling errors involved lymph node evaluation for metastatic carcinoma. CONCLUSIONS: Careful gross evaluation and microscopic examination of multiple levels should minimize specimen-sampling error and block-sampling error, respectively. Periodic review of accuracy and deferral rates may help reduce errors and improve the overall performance of this essential procedure.

Expression of p11 and TASK1 Channels in Rat Carotid Body Glomus Cells Subjected to Chronic Intermittent Hypoxia.

Chronic intermittent hypoxia (CIH) has been used as a model to mimic nocturnal apnea, which is associated with hypertension. One of the mechanisms for hypertension in patients with nocturnal apnea is an enhancement of the plasma membrane response to acute hypoxia in carotid body glomus cells. Hypoxia is known to induce depolarization via inhibiting TWIK-related acid-sensitive K+ (TASK) channels, one type of leak K+ channels, in glomus cells. The present experiment was undertaken to immunocytochemically investigate the effects of CIH on the expression and intracellular localization of TASK1 channels and p11 that critically affect the trafficking of TASK1 to the cell surface. The expression levels of TASK1 proteins and p11 and their intracellular localization in rat carotid body glomus cells were not noticeably affected by CIH, suggesting that the enhanced membrane response to acute hypoxia is not due to an increase in surface TASK channels.

Dual orexin receptor blocker suvorexant attenuates hypercapnic ventilatory augmentation in mice.

Suvorexant (Belsomra(R)), a dual orexin receptor antagonist widely used in the treatment of insomnia, inhibits the arousal system in the brain. However, the drug's ventilatory effects have not been fully explored. This study aims to investigate the expression of orexin receptors in respiratory neurons and the effects of suvorexant on ventilation. Immunohistology of brainstem orexin receptor OX2R expression was performed in adult mice (n = 4) in (1) rostral ventral respiratory group (rVRG) neurons projecting to the phrenic nucleus (PhN) retrogradely labeled by Fluoro-Gold (FG) tracer, (2) neurons immunoreactive for paired like homeobox 2b (Phox2b) in the parafacial respiratory group/retrotrapezoid nucleus (pFRG/RTN), and (3) neurons immunoreactive for neurokinin 1 receptor (NK1R) and somatostatin (SST) in the preBötzinger complex (preBötC). Additionally, we measured in vivo ventilatory responses to hyperoxic hypercapnia (5% CO2) and hypoxia (10% O2) before and after suvorexant pretreatment (10 and cumulative 100 mg/kg) in unrestrained mice (n = 10) in a body plethysmograph. We found the OX2R immunoreactive materials in pFRG/RTN Phox2b and preBötC NK1R/SST immunoreactive neurons but not in FG-labeled rVRG neurons, which suggests the involvement of orexin in respiratory control. Further, suvorexant expressly suppressed the hypercapnic ventilatory augmentation, otherwise unaffecting ventilation. Central orexin is involved in shaping the hypercapnic ventilatory chemosensitivity. Suppression of hypercapnic ventilatory augmentation by the orexin receptor antagonist suvorexant calls for caution in its use in pathologies that may progress to hypercapnic respiratory failure, or sleep-disordered breathing. Clinical trials are required to explore the role of targeted pharmacological inhibition of orexin in ventilatory pathologies.

Coherence analysis of the calcium activity of putative astrocytic and neuronal cells on the L5 ventral horn and neural output in activated lumbar CPG networks.

Astrocytes are thought to play a crucial role in providing structure to the spinal cord and maintaining efficient synaptic function and metabolism because their fine processes envelop the synapses of neurons and form many neuronal networks within the central nervous system (CNS). To investigate whether putative astrocytes and putative neurons distributed on the ventral horn play a role in the modulation of lumbar locomotor central pattern generator (CPG) networks, we used extracellular recording and optical imaging techniques and recorded the neural output from the left L5 ventral root and the calcium activity of putative astrocytes and neurons in the L5 ventral horn at the same time when activating an isolated L1-L5 spinal cord preparation from rats aged 0-2 days. Optical measurements detected cells that showed a fluorescence intensity change under all experimental conditions, namely, (1) 5-HT + NMDA, (2) TTX, and (3) TTX + Low K+. These cells were semiautomatically identified using an in-house MATLAB-based program, as putative astrocytes and neurons according to the cell classification, i.e., increased or decreased fluorescence intensity change (ΔF/F0), and subjective judgment based on their soma size. Coherence and its phase were calculated according to the calcium activity of the putative astrocytes and putative neurons, and neural output was calculated during fictive locomotion with in-house MATLAB-based programs. We found that the number of putative astrocytes activated by applying low K+ tends not to differ from that activated by applying the protease-activated receptor 1 (PAR1) selective agonist TFLLR-NH2 (TFLLR). Moreover, the calcium activity of several putative astrocytes and neurons synchronized with locomotor-like activity at a frequency range below 0.5 Hz and the time lag between peaks of cellular calcium activity and locomotor-like activity ranged from -1000 to + 1000 ms. These findings presumably indicates that these putative astrocytes and neurons in the left L5 ventral horn require -1000 to + 1000 ms to communicate with lumbar CPG networks and maintain efficient synaptic function and metabolism in activated lumbar CPG networks. This finding suggests the possibility that putative astrocytic and neuronal cells in the L5 ventral horn contribute to generating the rhythms and patterns of locomotor-like activity by activated CPG networks in the first to fifth lumbar spinal cord.

Interaction of the Left-Right Somatosensory Pathways in Patients With Thalamic Hemorrhage: A Case Report.

Neural plasticity compensates for the loss of motor function after stroke. However, whether neural plasticity occurs in the somatosensory pathways after stroke is unknown. We investigated the left-right somatosensory interaction in two hemorrhagic patients using a paired somatosensory evoked potentials (p-SEPs) recorded at CP3 and CP4, which was defined as an amplitude difference between the SEPs of paired median nerve stimulations to both sides and that of single stimulation to the affected side. Patient 1 (61-year-old, left thalamic hemorrhage) has a moderate motor impairment, severe sensory deficit, and complained of pain in the affected right upper limb. Patient 2 (72-year-old, right thalamic hemorrhage) had slight motor and sensory impairments with no complaints of pain. Single SEPs (s-SEPs) were obtained by stimulation of the right and left median nerves, respectively. For paired stimulations, 1 ms after the first stimulation to the non-affected side, followed by a second stimulation to the affected side. In patient 1, a s-SEP with stimulation to the non-affected side and a p-SEP were observed in CP4. However, a s-SEP was not observed in either hemisphere with stimulation to the affected side. On the other hand, in patient 2, a s-SEP in CP3 with stimulation to the non-affected side and in CP4 with stimulation to the affected side were observed; however, a p-SEP was not observed. In addition, to investigate the mechanism by which ipsilateral median nerve stimulation enhances contralateral p-SEP in patient 1, we compared the SEP averaged over the first 250 epochs with the SEP averaged over the second 250 epochs (total number of epochs recorded: 500). The results showed that in the patient 1, when the bilateral median nerve was stimulated continuously, the habituation did not occur and the response was larger than that of the s-SEP with unilateral median nerve stimulation. In the current case report, the damage to the thalamus may cause neuroplasticity in terms of the left-right interaction (e.g., left and right S1). The somatosensory input from the affected side may interfere with the habituation of the contralateral somatosensory system and conversely increase the response.

Activation of Astrocytes in the Persistence of Post-hypoxic Respiratory Augmentation.

Acute hypoxia increases ventilation. After cessation of hypoxia loading, ventilation decreases but remains above the pre-exposure baseline level for a time. However, the mechanism of this post-hypoxic persistent respiratory augmentation (PHRA), which is a short-term potentiation of breathing, has not been elucidated. We aimed to test the hypothesis that astrocytes are involved in PHRA. To this end, we investigated hypoxic ventilatory responses by whole-body plethysmography in unanesthetized adult mice. The animals breathed room air, hypoxic gas mixture (7% O2, 93% N2) for 2min, and again room air for 10min before and after i.p. administration of low (100mg/kg) and high (300mg/kg) doses of arundic acid (AA), an astrocyte inhibitor. AA suppressed PHRA, with the high dose decreasing ventilation below the pre-hypoxic level. Further, we investigated the role of the astrocytic TRPA1 channel, a putative ventilatory hypoxia sensor, in PHRA using astrocyte-specific Trpa1 knockout (asTrpa1 -/-) and floxed Trpa1 (Trpa1 f/f) mice. In both Trpa1 f/f and asTrpa1 -/- mice, PHRA was noticeable, indicating that the astrocyte TRPA1 channel was not directly involved in PHRA. Taken together, these results indicate that astrocytes mediate the PHRA by mechanisms other than TRPA1 channels that are engaged in hypoxia sensing.

Contralateral and Ipsilateral Interactions in the Somatosensory Pathway in Healthy Humans.

Hyper-adaptability, the ability to adapt to changes in the internal environment caused by neurological disorders, is necessary to recover from various disabilities, such as motor paralysis and sensory impairment. In the recovery from motor paralysis, the pre-existing neural pathway of the ipsilateral descending pathway, which is normally suppressed and preserved in the course of development, is activated to contribute to the motor control of the paretic limb. Conversely, in sensory pathways, it remains unclear whether there are compensatory pathways which are beneficial for the recovery of sensory impairment due to damaged unilateral somatosensory pathways, such as thalamic hemorrhage. Here, we investigated the interaction between the left and right somatosensory pathways in healthy humans using paired median nerve somatosensory evoked potentials (SEPs). Paired median nerve SEPs were recorded at CP3 and CP4 with a reference of Fz in the International 10-20 System. The paired median nerve stimulation with different interstimulus intervals (ISIs; 1, 2, 3, 5, 10, 20, 40, 60, and 100 ms) was performed to test the influence of the first stimulus (to the right median nerve) on the P14, P14/N20, and N20/P25 components induced by the second stimulus (left side). Results showed that the first stimulation had no effect on SEP amplitudes (P14, P14/N20, and N20/P25) evoked by the second stimulation in all ISI conditions, suggesting that there might not be a neural connectivity formed by a small number of synapses in the left-right interaction of the somatosensory pathway. Additionally, the somatosensory pathway may be less diverse in healthy participants.

Recent Insights into the Measurement of Carbon Dioxide Concentrations for Clinical Practice in Respiratory Medicine.

In the field of respiratory clinical practice, the importance of measuring carbon dioxide (CO2) concentrations cannot be overemphasized. Within the body, assessment of the arterial partial pressure of CO2 (PaCO2) has been the gold standard for many decades. Non-invasive assessments are usually predicated on the measurement of CO2 concentrations in the air, usually using an infrared analyzer, and these data are clearly important regarding climate changes as well as regulations of air quality in buildings to ascertain adequate ventilation. Measurements of CO2 production with oxygen consumption yield important indices such as the respiratory quotient and estimates of energy expenditure, which may be used for further investigation in the various fields of metabolism, obesity, sleep disorders, and lifestyle-related issues. Measures of PaCO2 are nowadays performed using the Severinghaus electrode in arterial blood or in arterialized capillary blood, while the same electrode system has been modified to enable relatively accurate non-invasive monitoring of the transcutaneous partial pressure of CO2 (PtcCO2). PtcCO2 monitoring during sleep can be helpful for evaluating sleep apnea syndrome, particularly in children. End-tidal PCO2 is inferior to PtcCO2 as far as accuracy, but it provides breath-by-breath estimates of respiratory gas exchange, while PtcCO2 reflects temporal trends in alveolar ventilation. The frequency of monitoring end-tidal PCO2 has markedly increased in light of its multiple applications (e.g., verify endotracheal intubation, anesthesia or mechanical ventilation, exercise testing, respiratory patterning during sleep, etc.).

Simple cubic self-assembly of PbS quantum dots by finely controlled ligand removal through gel permeation chromatography.

The geometry in self-assembled superlattices of colloidal quantum dots (QDs) strongly affects their optoelectronic properties and is thus of critical importance for applications in optoelectronic devices. Here, we achieve the selective control of the geometry of colloidal quasi-spherical PbS QDs in highly-ordered two and three dimensional superlattices: Disordered, simple cubic (sc), and face-centered cubic (fcc). Gel permeation chromatography (GPC), not based on size-exclusion effects, is developed to quantitatively and continuously control the ligand coverage of PbS QDs. The obtained QDs can retain their high stability and photoluminescence on account of the chemically soft removal of the ligands by GPC. With increasing ligand coverage, the geometry of the self-assembled superlattices by solution-casting of the GPC-processed PbS QDs changed from disordered, sc to fcc because of the finely controlled ligand coverage and anisotropy on QD surfaces. Importantly, the highly-ordered sc supercrystal usually displays unique superfluorescence and is expected to show high charge transporting properties, but it has not yet been achieved for colloidal quasi-spherical QDs. It is firstly accessible by fine-tuning the QD ligand density using the GPC method here. This selective formation of different geometric superlattices based on GPC promises applications of such colloidal quasi-spherical QDs in high-performance optoelectronic devices.

Sipuleucel-T associated inflammatory cardiomyopathy: a case report and observations from a large pharmacovigilance database.

AIMS: The major cardiovascular (CV) adverse effects observed with sipuleucel-T from large multi-institutional clinical trials included thromboembolic events, myocardial infarction, and congestive heart failure in up to 0.3% of patients with CV risk factors. The incidence, outcomes, and mechanisms in real-world clinical settings of these CV adverse effects to date have not been fully elucidated. Our study identified a patient with sipuleucel-T-induced inflammatory cardiomyopathy, which led to the identification of CV adverse effects associated with sipuleucel-T from a large pharmacovigilance database and elucidation of its potential mechanisms. METHODS AND RESULTS: Using the MedDRA term 'cardiac disorders' (System Organ Class level), CV adverse events associated with sipuleucel-T versus all other drugs were reviewed from VigiBase, a large pharmacovigilance database. Disproportionality analysis was calculated by the information component (IC), a Bayesian disproportionality indicator. A positive IC025 (IC 95% lower end credibility interval) value (>0) is the traditional threshold used in statistical signal detection at the Uppsala Monitoring Centre. From VigiBase, the total number of CV adverse drug reaction reported with sipuleucel-T was 306 out of a total of 22 980 104 adverse drug reactions in VigiBase on 10/25/2020. MedDRA preferred terms levels were grouped into major CV adverse drug reaction categories where we observed significant reports of myocardial ischaemia, supraventricular tachycardia (particularly atrial fibrillation/atrial flutter), congestive heart failure, and valvular disorders. Myocardial ischemia included acute myocardial infarction (IC025 2.3) with n = 4/26 (15%) of these individual case safety reports considered fatal. Among patients with 'cardiac failure congestive' (IC025 1.5), 11 of these 43 cases (26%) were fatal with 42 (98%) of these cases considered to be solely due to sipuleucel-T. CONCLUSIONS: Patients with CV risk factors who are receiving sipuleucel-T may be at higher risk for congestive heart failure, myocardial ischemia, and supraventricular tachycardia. Electrocardiograms during weekly sipuleucel-T infusions and left ventricular function monitoring with echocardiogram should be considered in these patients. Our findings are suggestive of another rare presentation of T-cell-mediated CV toxicity with cancer immunotherapy.

Donor-Derived Neuroendocrine Carcinoma Transmission to Two Kidney Transplant Recipients Demonstrated by Short Tandem Repeat Analysis: A Case Report.

Cancer transmission from a donor organ to a transplant recipient is a rare but not infrequently fatal event. We report a case of lung cancer transmission from a deceased donor to 2 kidney recipients. Approximately 1 year after uneventful kidney transplantation, both recipients developed acute kidney failure. Computed tomography imaging of abdomen and pelvis for both recipients showed masses in the transplanted kidneys along with innumerable masses in the livers. Pathologic examinations for both cases demonstrated high-grade neuroendocrine carcinoma with "mirror image" histologic findings in the transplant kidneys with liver metastases. Short tandem repeat (STR) analyses were performed to determine the origin of the tumors. STRs of both tumors were nearly identical to that of the donor, proving that both tumors were from the same donor. Immunohistochemical analyses showed that both tumors were positive for thyroid transcription factor 1, supporting a lung primary. One recipient died as a direct sequela to metastatic tumor, and the other required transplant nephrectomy and chemotherapy. Awareness of this largely nonpreventable complication and prompt molecular testing if cancer transmission is suspected are important.

Calcium Imaging Analysis of Cellular Responses to Hypercapnia and Hypoxia in the NTS of Newborn Rat Brainstem Preparation.

It is supposed that the nucleus of the solitary tract (NTS) in the dorsal medulla includes gas sensor cells responsive to hypercapnia or hypoxia in the central nervous system. In the present study, we analyzed cellular responses to hypercapnia and hypoxia in the NTS region of newborn rat in vitro preparation. The brainstem and spinal cord were isolated from newborn rat (P0-P4) and were transversely cut at the level of the rostral area postrema. To detect cellular responses, calcium indicator Oregon Green was pressure-injected into the NTS just beneath the cut surface of either the caudal or rostral block of the medulla, and the preparation was superfused with artificial cerebrospinal fluid (25-26°C). We examined cellular responses initially to hypercapnic stimulation (to 8% CO2 from 2% CO2) and then to hypoxic stimulation (to 0% O2 from 95% O2 at 5% CO2). We tested these responses in standard solution and in two different synapse blockade solutions: (1) cocktail blockers solution including bicuculline, strychnine, NBQX and MK-801 or (2) TTX solution. At the end of the experiments, the superfusate potassium concentration was lowered to 0.2 from 3 mM to classify recorded cells into neurons and astrocytes. Excitation of cells was detected as changes of fluorescence intensity with a confocal calcium imaging system. In the synaptic blockade solutions (cocktail or TTX solution), 7.6 and 8% of the NTS cells responded to hypercapnic and hypoxic stimulation, respectively, and approximately 2% of them responded to both stimulations. Some of these cells responded to low K+, and they were classified into astrocytes comprising 43% hypercapnia-sensitive cells, 56% hypoxia-sensitive cells and 54% of both stimulation-sensitive cells. Of note, 49% of the putative astrocytes identified by low K+ stimulation were sensitive to hypercapnia, hypoxia or both. In the presence of a glia preferential blocker, 5 mM fluoroacetate (plus 0.5 µM TTX), the percentage of hypoxia-sensitive cells was significantly reduced compared to those of all other conditions. This is the first study to reveal that the NTS includes hypercapnia and hypoxia dual-sensitive cells. These results suggest that astrocytes in the NTS region could act as a central gas sensor.

Age-Related Differences in Strategy in the Hand Mental Rotation Task.

Mental imagery of movement is a potentially valuable rehabilitation task, but its therapeutic efficacy may depend on the specific cognitive strategy employed. Individuals use two main strategies to perform the hand mental rotation task (HMRT), which involves determining whether a visual image depicts a left or right hand. One is the motor imagery (MI) strategy, which involves mentally simulating one's own hand movements. In this case, task performance as measured by response time (RT) is subject to a medial-lateral effect wherein the RT is reduced when the fingertips are directed medially, presumably as the actual motion would be easier. The other strategy is to employ visual imagery (VI), which involves mentally rotating the picture and is not subject to this medial-lateral effect. The rehabilitative benefits of the HMRT are thought to depend on the MI strategy (mental practice), so it is essential to examine the effects of individual factors such as age, image perspective (e.g., palm or back of the hand), and innate ability (as indicated by baseline RT) on the strategy adopted. When presented with pictures of the palm, all subjects in the current study used the MI strategy, regardless of age and ability. In contrast, when subjects were presented with pictures of the back of the hand, the VI strategy predominated among the young age group regardless of performance, while the strategy used by middle-age and elderly groups depended on performance ability. In the middle-age and elderly groups, the VI approach predominated in those with high performance skill, whereas the MI strategy predominated among those with low performance skill. Thus, higher-skill middle-aged and elderly individuals may not necessarily form a motion image during the HMRT, potentially limiting rehabilitation efficacy.