Non-specific blood tests as proxies for COVID-19 hospitalisation: are there plausible associations after excluding noisy predictors?

This study applied causal criteria in directed acyclic graphs for handling covariates in associations for prognosis of severe coronavirus disease 2019 (COVID-19) cases. To identify non-specific blood tests and risk factors as predictors of hospitalisation due to COVID-19, one has to exclude noisy predictors by comparing the concordance statistics (area under the curve - AUC) for positive and negative cases of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Predictors with significant AUC at negative stratum should be either controlled for their confounders or eliminated (when confounders are unavailable). Models were classified according to the difference of AUC between strata. The framework was applied to an open database with 5644 patients from Hospital Israelita Albert Einstein in Brazil with SARS-CoV-2 reverse transcription - polymerase chain reaction (RT-PCR) exam. C-reactive protein (CRP) was a noisy predictor: hospitalisation could have happened due to causes other than COVID-19 even when SARS-CoV-2 RT-PCR is positive and CRP is reactive, as most cases are asymptomatic to mild. Candidates of characteristic response from moderate-to-severe inflammation of COVID-19 were: combinations of eosinophils, monocytes and neutrophils, with age as risk factor; and creatinine, as risk factor, sharpens the odds ratio of the model with monocytes, neutrophils and age.

Long-term analgesic effect of a single dose of anti-NGF antibody on pain during motion without notable suppression of joint edema and lesion in a rat model of osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) patients experience exaggerated pain during movements such as walking. Anti-nerve growth factor (NGF) antibodies have recently shown analgesic effects in OA patients. We examined the effect of a single dose of anti-NGF antibody on pain during motion, joint edema and lesion in a rat model of OA to determine whether the analgesic effect demonstrated in clinical studies can be translated to a preclinical model. METHODS: Sodium monoiodoacetate (MIA)-induced arthritic rats that develop a right-left gait imbalance when walking as an index of pain during motion. This imbalance was assessed using a gait analysis system called "CatWalk". Edema size and lesion score in the relevant knee joint were also measured. The effect of a single intravenous injection of an anti-NGF monoclonal antibody AS2886401-00 on these parameters was assessed. RESULTS: AS2886401-00 administered at 0.3 or 1 mg/kg on Day 3 post-MIA injection resulted in a statistically significant improvement in gait imbalance even on Day 35. When gait measurement was set on Week 3 post-MIA administration, administration of the antibody at a timing close to the gait measurement, i.e., 1 or 24 h prior to the measurement, was less effective. AS2886401-00 did not suppress either edema or lesion. CONCLUSIONS: A single dose of anti-NGF antibody exerts a long-lasting analgesic effect on pain during motion in a rat model of OA. This finding could be associated with the analgesic efficacies that anti-NGF antibodies have exhibited in clinical studies. It appears unlikely that analgesia is secondary to inhibition of joint edema and lesion.

Endothelial expression of Fc gamma receptor IIb in the full-term human placenta.

In the third trimester, human placental endothelial cells express Fc gamma receptor IIb (FcgammaRIIb). This expression is unique because FcgammaRIIb is generally expressed on immune cells and is typically undetectable in adult endothelial cells. Recently, we found a novel FcgammaRIIb-defined, IgG-containing organelle in placental endothelial cells; this organelle may be a key structure for the transcytosis of IgG across the endothelial layer. In this study, we verify the expression of FcgammaRIIb in endothelial placenta cells and use reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing analyses to define the expressed FCGR2B mRNA transcript variant. We also investigated the distribution of FCGR2B mRNA and protein within the vascular tree of the full-term human placenta by RT-PCR and quantitative microscopy. The mRNA sequence of FCGR2B expressed specifically in placental endothelial cells is that of transcript variant 2. FcgammaRIIb expression and synthesis occur throughout the placental vascular tree but do not extend into the umbilical cord. This study provides additional information on FcgammaRIIb expression in the human placenta.

Proteome analysis of human placentae: pre-eclampsia versus normal pregnancy.

Although placental proteins play multiple roles in fetal and placental development and in the maintenance of pregnancy, many remain inadequately characterized. In the present study, we comprehensively analyzed these proteins by using a proteomic approach. Samples were denatured with guanidine hydrochloride, which was found to be superior to the commonly used urea for the present purpose, and subjected to 2-dimensional (2D) electrophoresis (2-DE) to obtain placental proteome maps. The identified protein spots (ca. 60% of the total) on the proteome maps included several pregnancy-related proteins (PRPs). Furthermore, a novel 2D immunoblotting (2-DI) analysis of molecules related to pre-eclampsia revealed three immunopositive spots that appeared to correspond to dynactin p-50, a protein related to cell turn-over. The rate of positivity for dynactin p-50-reactive antibodies was significantly (P=0.0024) higher in 26 pre-eclamptic women than in 58 normally pregnant women. These results indicate that dynactin p-50 may be involved in the pathophysiology of pre-eclampsia.

Enhancing effect of high dietary iron on lung tumorigenesis in mice.

In our previous reports we indicated that oxidative stress on pulmonary nuclei caused by oxy radicals could be involved in glycerol-enhanced lung tumorigenesis in ddY mice treated with 4-nitroquinoline 1-oxide (4NQO). This study was undertaken to estimate if dietary iron could act as a stimulating factor on lung tumorigenesis in mice treated with 4NQO plus glycerol. Feeding excessive iron to mice treated with these agents significantly increased nuclear thiobarbituric acid reactive substances (TBARS) and DNA single strand breaks (DNA-SSB) in the lungs as compared with mice fed adequate iron 4 weeks after 4NQO injection. Nuclear non-haem iron level in mice fed excessive iron was also higher than the level in mice fed adequate iron. Twenty-three weeks after 4NQO injection (at the end of this experiment) the supply of excessive iron for 4 and 23 weeks after 4NQO injection stimulated the development of lung tumors in mice treated with 4NQO plus glycerol. These results suggest that a high dietary iron level acts as a stimulating factor on lung tumorigenesis in mice treated with 4NQO plus glycerol.

Primary structure and function of superoxide dismutase from the ascidian Halocynthia roretzi.

A protein with a molecular weight of 17K, immunoreactive with the S-1B2 antibody, has been isolated from hemocytes of Halocynthia roretzi. Its amino acid sequence has been determined by sequential Edman degradation analysis of peptide fragments derived from proteolytic fragmentation. The 17K protein is a single chain protein consisting of 151 amino acids with an acylated N-terminal serine. A comparison of the amino acid sequence of H. roretzi 17K protein with those of other proteins reveals that the 17K protein is Cu,Zn-SOD. The protein was found to have a KCN-inhibited SOD activity. Cu,Zn-SOD has been purified from H. roretzi plasma. The molecular weight is 17K and the activity is inhibited with KCN and diethyldithiocarbamate. It has been demonstrated that it can enhance phagocytosis by H. roretzi hemocytes. Thus, plasma Cu,Zn-SOD plays a role in H. roretzi as a defense molecule.

The prevention of oxy radical-mediated lung tumorigenesis in mice by vitamin E.

This work was carried out to estimate the preventive effect of vitamin E on oxy radical-enhanced lung tumorigenesis in ddY mice. We have reported that oxy radicals could be an important factor contributing to the promotive effect of glycerol on 4-nitroquinoline 1-oxide (4NQO)-induced lung tumorigenesis (1). The glycerol-promoted lung tumorigenesis of mice treated with 4NQO was reduced in mice feeding on excessive vitamin E in this study. The levels of nuclear thiobarbituric acid reactive substances (TBARS) and oxidative damage of DNA estimated as DNA single strand breaks (DNA-SSB) were significantly higher in the lungs of mice treated with 4NQO + glycerol than in those treated with 4NQO at 4 weeks after 4NQO administration, This increase was suppressed by the feeding of excessive vitamin E for 4 weeks after 4NQO injection. At 23 weeks after 4NQO injection, the feeding of excessive vitamin E for 4 and 23 weeks after 4NQO injection could cancel the promotive effect of glycerol on lung tumorigenesis. Additionally, the alpha-tocopherol level in serum was related with the degree of lung tumorigenesis at 23 weeks after 4NQO injection. These findings suggest that vitamin E can act as a useful agent to protect mice from oxy radical-promoted lung tumorigenesis.

Effect of vitamin E on 4-nitroquinoline 1-oxide-induced lung tumorigenesis in mice.

Oxidative stress may play a partial role in chemically induced tumorigenesis in mice. Herein, we investigated the preventive effect of vitamin E on 4-nitroquinoline 1-oxide (4NQO)-induced oxidative damage on pulmonary nuclei and lung tumorigenesis in mice. At 4 weeks after 4NQO injection, the levels of nuclear thiobarbituric acid substances (TBARS) and DNA single strand breaks (DNA-SSB) in the lungs of mice treated with 4NQO were significantly higher than those in the control mice. The 4NQO-induced oxidative stress on the nuclei and DNA-SSB were significantly inhibited by vitamin E treatment. The nuclear alpha-tocopherol level in the 4NQO-treated group was significantly lower than that in the control, but the plasma alpha-tocopherol level in the former was slightly lower than that in the latter. Vitamin E feeding compensated the decrease of the level in the nuclei and plasma. The feeding on excessive vitamin E for 23 weeks after 4NQO injection could partly reduce the lung tumor incidence as well as lung tumor multiplicity in mice. These findings suggest that vitamin E could partly suppress 4NQO-induced lung tumorigenesis in mice, probably through the inhibition of 4NQO-induced oxidative damage on the nuclei.

Prediction of uterine dehiscence by measuring lower uterine segment thickness prior to the onset of labor: evaluation by transvaginal ultrasonography.

OBJECTIVE: Lower uterine segment thickness was measured by transvaginal ultrasound examination and its correlations with the occurrence of uterine dehiscence and rupture was examined. METHODS: The thickness of the muscular layer of the lower uterine segment was measured in 186 term gravidas with previous uterine scars and its correlation with uterine dehiscence/rupture was investigated. RESULTS: Uterine dehiscence was found in 9 cases or 4.7%. There were no cases of the uterine rupture. The thickness of the lower uterine segment among the gravidas with dehiscence was significantly less in than those without dehiscence (p< 0.01). The cut-off value for the thickness of the lower uterine segment was 1.6 mm as calculated by the receiver operating characteristic curve. The sensitivity was 77.8%; specificity 88.6%; positive predictive value 25.9%; negative predictive value 98.7%. CONCLUSION: Measurement of the lower uterine segment is useful in predicting the absence of dehiscence among gravidas with previous cesarean section. If the thickness of the lower uterine segment is more than 1.6 mm, the possibility of dehiscence during the subsequent trials of labor is very small.

[The effect of hypertonic saline infusion on lumbar epidural anesthesia].

The author compared hemodynamic effects of fluid loading during epidural anesthesia with 7.2% hypertonic saline (HS), lactate Ringer's (LR) or isotonic saline solutions in 24 ASA 1 patients undergoing elective lower abdominal or pelvic surgery, allocated randomly into three groups. The first two groups, patients received equal amounts of sodium (2.2 mmol.kg-1), and the latter group, isotonic saline solutions for 1-2 ml.kg-1.h-1 as control. After epidural injection (2%mepivacaine 0.1 ml.cm(Height)-1), fluid loading was performed for 20 minutes. The volume of fluid loading was significantly larger in group LR (979.3 +/- 154.7 ml) than the other two groups (HS: 104.5 +/- 20.0 ml, NS: 48.8 +/- 8.3 ml) (P < 0.05). The number of blocked segments was similar in three groups. Magnitude of hypotension was no significantly different among the groups 20 minutes after fluid loading, but recovered to the control level in group HS. In all groups heart rate decreased but the decrease was significant only in group HS. But, in group HS, stroke index increased after fluid loading and remained elevated. Increase of extracellular volume in group HS was observed by bioelectrical impedance analysis as in group LR. The author concludes that HS may be useful especially in the case not requiring a large volume of fluid loading. Finding ideal concentration, volume, and speed of infusion of intravenous fluids would be clinically useful.

[A case of using continuous double-tapped epidural analgesia for herpes zoster duplex].

A 66-year-old woman developed herpes zoster duplex, which is a rare disease. She had severe pain at the right upper back area and left lower abdominal area. The authors used double-tapped continuous epidural analgesia for this patient. The catheters for the epidural block were placed at the 8th thoracic vertebral level and 2nd lumbar vertebral level. After the start of continuous epidural block, she suffered from nausea, vomited, and felt dizzy. It was evident that these symptoms were caused by local anesthetic toxicity. We emphasize that we must pay attention to the patient who undergoes continuous double-tapped epidural analgesia for pain relief so as not to elicit local anesthetic toxicity.

[A case of atopic dermatitis treated with stellate ganglion block--the change of serum IgE and blood eosinophil levels].

Stellate ganglion block (SGB) therapy was tried on a patient with severe adult type atopic dermatitis. SGB was performed 102 times in total and clinical symptoms improved gradually. Serum IgE and blood eosinophil levels, which correlate with disease severity, increased gradually following repeated SGB. After a series of SGB was stopped, clinical symptoms became worse and serum IgE and blood eosinophil levels increased again. We conclude that although SGB is presumably one of the effective therapies for severe adult type atopic dermatitis, it might be difficult to improve atopic constitution entirely because the patient was not cured completely following repeated SGB.

[Changes in dementia rating scale scores of elderly patients with femoral neck fracture during perioperative period].

We evaluated changes in dementia rating scale scores in the revised version of Hasegawa's dementia scale (HDS-R), and rated dementia, 2 days before and 7 days after surgery in the elderly patients with femoral neck fracture. The 50 patients examined ranged in age from 70 years to 101 years. A perfect score in the HDS-R is 30 points, and a score below 20 points strongly suggests dementia. The results were as follows. In septuagenarian and octogenarian patients, the scale score was higher after surgery than the value before the surgery. Although the preoperative and postoperative scores of the patients who had been under epidural anesthesia were not significantly different, the score of patients who had been under general anesthesia was higher in the postoperative period than in the preoperative period. In octogenarian patients, there was a negative correlation between "postoperative score minus preoperative score" and "the number of the days from suffering fracture to surgery". These results showed that general anesthesia is more advantageous than epidural anesthesia from the viewpoint of the intellectual faculty in septuagenarian and octogenarian patients with femoral neck fracture, and it is within the bounds of possibility that the intellectual faculty may decline if an octogenarian patient is operated after a long delay from the occurrence of fracture. To prevent this decline, patients must be operated on as soon as possible.

Note: Absolute detection efficiency of a tapered microchannel plate for Ne⁺ ions.

The absolute detection efficiency of a tapered microchannel plate with an open-area ratio of 90% was measured for Ne(+) with energies up to 5 keV, and comparison with the results for Xe(+) was made. As in the case of Xe(+), the maximum detection efficiency was 90%. The energy dependence of the efficiency curves normalized with respect to the open-area ratios was examined based on the scaling law proposed previously.

Automated measurement of spontaneous pain-associated limb movement and drug efficacy evaluation in a rat model of neuropathic pain.

BACKGROUND: The withdrawal response elicited by a nociceptive stimulus, i.e., evoked pain measure, is commonly used as an efficacy endpoint in neuropathic pain animal models. It, however, has several limitations, which highlight the importance of examining spontaneous pain. The present study describes an automated method for measuring spontaneous pain behaviour in a rat model of neuropathic pain caused by chronic constriction injury (CCI) of sciatic nerve. METHODS: After CCI surgery, a small magnet was implanted into the operated limb. The rat was placed in a test chamber that was surrounded by wire coil. Limb movements, including lifting/guarding, flinching/shaking, licking and walking in the operated limb, caused changes in the electromagnetic field, including a change in voltage and transformed into a signal via an amplifier. RESULTS: CCI rats consistently showed more frequent limb movement than sham rats. There was no significant correlation between the frequency of spontaneous pain behaviour and the evoked pain symptoms. Treatment with duloxetine (30 mg/kg p.o.) and amitriptyline (30 and 100 mg/kg p.o.) significantly reduced this frequency. Pregabalin at 30 mg/kg p.o. tended to reduce the frequency, and diclofenac up to 10 mg/kg p.o. had no effect. CONCLUSION: A non-subjective automated method for measuring spontaneous pain behaviour in an animal model of neuropathic pain was established. It is expected that the current system will greatly enhance the analysis of spontaneous pain-related behaviour, which is a predominant symptom in patients with neuropathic pain. The current system may also be valuable in the screening of potential analgesic treatments.