Occurrence and Exposure Assessment of Lipophilic Shellfish Toxins in the Zhejiang Province, China.

Although lipophilic shellfish toxins (LSTs) pose a significant threat to the health of seafood consumers, their systematic investigation and risk assessment remain scarce. The goals of this study were as follows: (1) analyze LST levels in commercially available shellfish in Zhejiang province, China, and determine factors influencing LST distribution; (2) assess the acute dietary risk of exposure to LSTs for local consumers during the red tide period; (3) explore potential health risks of LSTs in humans; and (4) study the acute risks of simultaneous dietary exposure to LSTs and paralytic shellfish toxins (PSTs). A total of 546 shellfish samples were collected. LSTs were detected in 89 samples (16.3%) at concentrations below the regulatory limits. Mussels were the main shellfish species contaminated with LSTs. Spatial variations were observed in the yessotoxin group. Acute exposure to LSTs based on multiple scenarios was low. The minimum tolerable exposure durations for LSTs calculated using the mean and the 95th percentile of consumption data were 19.7 and 4.9 years, respectively. Our findings showed that Zhejiang province residents are at a low risk of combined exposure to LSTs and PSTs; however, the risk may be higher for children under 6 years of age in the extreme scenario.

Mortality prediction and influencing factors for intensive care unit patients with acute tubular necrosis: random survival forest and cox regression analysis.

Background: Patients with acute tubular necrosis (ATN) not only have severe renal failure, but also have many comorbidities, which can be life-threatening and require timely treatment. Identifying the influencing factors of ATN and taking appropriate interventions can effectively shorten the duration of the disease to reduce mortality and improve patient prognosis. Methods: Mortality prediction models were constructed by using the random survival forest (RSF) algorithm and the Cox regression. Next, the performance of both models was assessed by the out-of-bag (OOB) error rate, the integrated brier score, the prediction error curve, and area under the curve (AUC) at 30, 60 and 90 days. Finally, the optimal prediction model was selected and the decision curve analysis and nomogram were established. Results: RSF model was constructed under the optimal combination of parameters (mtry = 10, nodesize = 88). Vasopressors, international normalized ratio (INR)_min, chloride_max, base excess_min, bicarbonate_max, anion gap_min, and metastatic solid tumor were identified as risk factors that had strong influence on mortality in ATN patients. Uni-variate and multivariate regression analyses were used to establish the Cox regression model. Nor-epinephrine, vasopressors, INR_min, severe liver disease, and metastatic solid tumor were identified as important risk factors. The discrimination and calibration ability of both predictive models were demonstrated by the OOB error rate and the integrated brier score. However, the prediction error curve of Cox regression model was consistently lower than that of RSF model, indicating that Cox regression model was more stable and reliable. Then, Cox regression model was also more accurate in predicting mortality of ATN patients based on the AUC at different time points (30, 60 and 90 days). The analysis of decision curve analysis shows that the net benefit range of Cox regression model at different time points is large, indicating that the model has good clinical effectiveness. Finally, a nomogram predicting the risk of death was created based on Cox model. Conclusion: The Cox regression model is superior to the RSF algorithm model in predicting mortality of patients with ATN. Moreover, the model has certain clinical utility, which can provide clinicians with some reference basis in the treatment of ATN and contribute to improve patient prognosis.

Occurrence and Exposure Assessment of Nickel in Zhejiang Province, China.

Nickel (Ni) is a silver-white metal with high antioxidative properties, often existing in a bivalent form in the environment. Despite being the fifth most abundant metal on Earth, anthropogenic activities, including industrial processes, have elevated Ni levels in environmental media. This study investigated Ni contamination in various food groups in Zhejiang Province, China, mainly focusing on Ni levels in beans, vegetables, aquatic foods, meat products, cereal products, and fruits. A total of 2628 samples were collected and analyzed. Beans exhibited the highest Ni content in all samples. The overall detection rate of Ni was 86.5%, with variation among food categories. For plant-origin foods, legumes had the highest Ni concentration while for animal-origin foods, shellfish showed the highest median Ni concentration. The results indicate generally acceptable Ni exposure levels among Zhejiang residents, except for children aged 0-6. Beans were identified as the primary contributor to high Ni exposure risk. The paper suggests monitoring Ni contamination in food, especially for vulnerable populations, and provides insights into exposure risks in different age groups.

An Occurrence and Exposure Assessment of Paralytic Shellfish Toxins from Shellfish in Zhejiang Province, China.

The intake of paralytic shellfish toxins (PSTs) may adversely affect human health. Therefore, this study aimed to show the prevalence of PSTs from commercially available shellfish in Zhejiang Province, China, during the period of frequent red tides, investigate the factors affecting the distribution of PSTs, and assess the risk of PST intake following the consumption of bivalve shellfish among the Zhejiang population. A total of 546 shellfish samples were collected, 7.0% of which had detectable PSTs at concentrations below the regulatory limit. Temporal, spatial, and interspecific variations in the occurrence of PSTs were observed in some cases. The dietary exposure to PSTs among the general population of consumers only was low. However, young children in the extreme scenario (the 95th percentile of daily shellfish consumption combined with the maximum PST concentration), defined as 89-194% of the recommended acute reference doses, were possibly at risk of exposure. Notably, Arcidae and mussels were the major sources of exposure to toxins. From the public health perspective, PSTs from commercially available shellfish do not pose a serious health risk; however, more attention should be paid to acute health risks, especially for young children, during periods of frequent red tides.

Could C3, 4, and 5 Nerve Root Block be a Better Alternative to Interscalene Block Plus Intermediate Cervical Plexus Block for Patients Undergoing Surgery for Midshaft and Medial Clavicle Fractures? A Randomized Controlled Trial.

BACKGROUND: Variable innervation of the clavicle is a major challenge in surgery of clavicle fractures with patients under regional anesthesia. An interscalene block (ISB) combined with an intermediate cervical plexus block (ICPB) provides analgesia in clavicle fracture surgery, but this combination does not completely block sensation in the midshaft or medial clavicle. Cervical nerve root block is an alternative to deep cervical plexus block and has recently been used as an analgesic method in the neck and shoulder. Whether it should be used as an alternative for midshaft and medial clavicle fractures is unknown. QUESTIONS/PURPOSES: In this randomized controlled trial, we compared a C3, 4, and 5 nerve root block to ISB combined with ICPB in surgery of midshaft and medial clavicle fractures in terms of the (1) proportion of patients achieving a sensory block that is sufficient for surgery, (2) onset time and duration of the block, and (3) effectiveness of postoperative analgesia, as measured by pain scores and consumption of analgesics. METHODS: Between November 2021 and December 2021, we treated 154 patients for clavicle fractures. A total of 122 were potentially eligible, 91 of whom agreed to participate in this study. Twenty-nine patients were excluded because the patients chose general anesthesia or declined to undergo surgery. Ultimately, 62 patients were randomly allocated into the C3, 4, and 5 group or ISB + ICPB group, with 31 patients in each group; there were no dropouts. All patients were analyzed in the group they were randomized to under intention-to-treat principles. The assessor and patients were blinded to randomization throughout the trial. The two groups did not differ in any important ways, including age, gender, BMI, American Society of Anesthesiologists classification, and type of clavicle fracture. The two groups received either an ultrasound-guided C3, 4, and 5 nerve root block with 2, 3, and 5 mL of 0.5% ropivacaine or ultrasound-guided ISB with ICPB with 20 mL of 0.5% ropivacaine. The primary outcome was the proportion of patients in each group with a successful nerveba block who did not receive general anesthesia; this was defined as nerve block success. Secondary outcomes included the onset time and duration of the sensory block, defined as the onset to the moment when the patients felt pain and sought rescue analgesia; pain assessment in terms of the numeric rating scale (NRS) score (range 0 to 10) for pain after nerve block before and during surgery; and the median amount of sufentanil consumed intraoperatively and postoperatively in the recovery room. The dosing of sufentanil was determined by the assessor when the NRS score was 1 to 3 points. If the NRS score was more than 3 points, general anesthesia was administered as a rescue method. Complications after the two inventions such as toxic reaction, dyspnea, hoarseness, pneumothorax, and Horner syndrome were also recorded in this study. RESULTS: A higher proportion of patients in the C3, 4, and 5 group had a successful nerve block than in the ISB + ICPB group (97% [30 of 31] versus 68% [21 of 31], risk ratio 6 [95% CI 1.5 to 37]; p < 0.01). The median onset time was 2.5 minutes (range 2.0 to 3.0 minutes) in the C3, 4, and 5 group and 12 minutes (range 9 to 16 minutes) in the ISB + ICPB group (difference of medians 10 minutes; p < 0.001). The sensory block duration was 10 ± 2 hours in the C3, 4, and 5 group and 8 ± 2 hours in the ISB + ICPB group (mean difference 2 hours [95% CI 1 to 3 hours]; p < 0.001). The median sufentanil consumption was lower in the C3, 4, 5 group than in the ISB + ICPB (median 5 µg [range 0.0 to 5.0 µg] versus median 0 µg [range 0.0 to 0.0 µg]; difference of medians 5.0 µg; p < 0.001). There were no differences between the two groups regarding NRS scores after nerve blocks and NRS score for incision and periosteum separation, with the minimum clinically important difference set at a 2-point difference (of 10). There were no severe complications in this study. CONCLUSION: Based on our analysis of the data, a C3, 4, and 5 nerve root block was better than ISB combined with ICPB for surgery to treat medial shaft and medial clavicle fractures. When choosing the anesthesia method, however, the patient's basic physiologic condition and possible complications should be considered. LEVEL OF EVIDENCE: Level I, therapeutic study.

Nicotinic Acetylcholine Receptors are Associated with Ketamine-induced Neuronal Apoptosis in the Developing Rat Retina.

Early synchronized spontaneous network activity is a hallmark of the brain growth spurt period, during which general anesthetics cause widespread neuronal apoptosis and subsequent cognitive dysfunction. However, the relationship of such activity to anesthetic-induced neuronal apoptosis remains to be determined. In this study, we utilized patch-clamp electrophysiological recording, immunohistochemistry, and TUNEL assays to investigate the potential roles of spontaneous network activity in ketamine-induced neuronal apoptosis during early development. All experiments were performed using acutely dissected whole-mount Sprague-Dawley rat retinas (0-14 postnatal days [P0-P14]). Ketamine reversibly blocked spontaneous network activity in the rat retina from P0 to P9 and irreversibly blocked such activity from P10 to P12. The peak of physiological and ketamine-induced neuronal apoptosis mainly occurred from P7 to P9. Blockade of nicotinic acetylcholine receptors (nAChRs) also induced reversible inhibition of spontaneous network activity from P0 to P7 and extensive neuronal apoptosis in the P7 rat retina, while activation of nAChRs or increases in endogenous ACh levels attenuated ketamine-induced apoptotic responses. Furthermore, blockade of α7-nAChR and ß2-nAChR subtypes induced neuronal apoptosis in the developing retina, while activation of the α7-nAChR subtype attenuated ketamine-induced apoptotic responses. These results demonstrate that ketamine may inhibit early synchronized spontaneous network activity by blocking nAChRs, and that such inhibition may contribute to ketamine-induced neuronal apoptosis in the developing rat retina.

The expression profile of developmental stage-dependent circular RNA in the immature rat retina.

PURPOSE: Physiologic neuronal apoptosis, which facilitates the developmental maturation of the nervous system, is regulated by neuronal activity and gene expression. Circular RNA (circRNA), a class of non-coding RNA, regulates RNA and protein expression. As the relationship between circRNA and apoptosis is unknown, we explored changes in expression patterns of circRNA during physiologic neuronal apoptosis. METHODS: High-throughput sequencing was used to explore changes in the expression of circRNA in the postnatal developing rat retina. Neuronal apoptosis was determined with immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in the rat retinal ganglion cell layer. RESULTS: In total, 2,654, 7,201, and 5,628 circRNA species were detected in the postnatal day (P)3, P7, and P12 rat retina, respectively. Of these circRNA species, 1,371 changed statistically significantly between P3 and P7 and 1,112 changed statistically significantly between P7 and P12. Normal developmental apoptosis, measured with the ratio of apoptotic (caspase-3- or TUNEL-positive) cells to normal cells, showed an increase from P3 to P7 and then a reduction from P7 to P12. In addition, 15 circRNAs whose host genes were associated with apoptosis were differentially expressed during the early development period. CONCLUSIONS: These results associate circRNAs with neuronal apoptosis, providing potential mechanisms and treatment targets for physiologic and drug-induced apoptosis in the developing nervous system.

Dopamine attenuates ethanol-induced neuroapoptosis in the developing rat retina via the cAMP/PKA pathway.

Apoptosis has been identified as the primary cause of fetal alcohol spectrum disorder (FASD), and the development of methods to prevent and treat FASD have been based on the mechanisms of alcohol-induced apoptosis. The present study aimed to explore the effects of dopamine on alcohol­induced neuronal apoptosis using whole­mount cultures of rat retinas (postnatal day 7). Retinas were initially incubated with ethanol (100, 200 or 500 mM), and in subsequent analyses retinas were co­incubated with ethanol (200 mM) and dopamine (10 µM). In addition, several antagonists and inhibitors were used, including a D1 dopamine receptor (D1R) antagonist (SCH23390; 10 µM), a D2R antagonist (raclopride; 40 µM), an adenosine A2A receptor (AA2AR) antagonist (SCH58261; 100 nM), an adenylyl cyclase (AC) inhibitor (SQ22536; 100 µM) and a PKA inhibitor (H­89; 1 µM). The results demonstrated that exposure increased neuroapoptosis in the retinal ganglion cell layer (GCL) in a dose­dependent manner. Dopamine treatment significantly attenuated ethanol­induced neuronal apoptosis. D1R, D2R and AA2AR antagonists partially inhibited the protective effects of dopamine against ethanol­induced apoptosis; similar results were observed with AC and PKA inhibitor treatments. In summary, the present study demonstrated that dopamine treatment may be able to attenuate alcohol­induced neuroapoptosis in the developing rat retina by activating D1R, D2R and AA2AR, and by upregulating cyclic AMP/protein kinase A signaling.

Dopamine Attenuates Ketamine-Induced Neuronal Apoptosis in the Developing Rat Retina Independent of Early Synchronized Spontaneous Network Activity.

Deprivation of spontaneous rhythmic electrical activity in early development by anesthesia administration, among other interventions, induces neuronal apoptosis. However, it is unclear whether enhancement of neuronal electrical activity attenuates neuronal apoptosis in either normal development or after anesthesia exposure. The present study investigated the effects of dopamine, an enhancer of spontaneous rhythmic electrical activity, on ketamine-induced neuronal apoptosis in the developing rat retina. TUNEL and immunohistochemical assays indicated that ketamine time- and dose-dependently aggravated physiological and ketamine-induced apoptosis and inhibited early-synchronized spontaneous network activity. Dopamine administration reversed ketamine-induced neuronal apoptosis, but did not reverse the inhibitory effects of ketamine on early synchronized spontaneous network activity despite enhancing it in controls. Blockade of D1, D2, and A2A receptors and inhibition of cAMP/PKA signaling partially antagonized the protective effect of dopamine against ketamine-induced apoptosis. Together, these data indicate that dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina by activating the D1, D2, and A2A receptors, and upregulating cAMP/PKA signaling, rather than through modulation of early synchronized spontaneous network activity.