An inhaled ACE2 decoy confers protection against SARS-CoV-2 infection in preclinical models.

The Omicron variant continuously evolves under the humoral immune pressure exerted by vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the resulting Omicron subvariants display further immune evasion and antibody escape. An engineered angiotensin-converting enzyme 2 (ACE2) decoy composed of high-affinity ACE2 and an IgG1 Fc domain could offer an alternative modality to neutralize SARS-CoV-2. We previously reported its broad spectrum and therapeutic potential in rodent models. Here, we demonstrate that the engineered ACE2 decoy retains neutralization activity against Omicron subvariants, including the currently emerging XBB and BQ.1 strains, which completely evade antibodies currently in clinical use. SARS-CoV-2, under the suboptimal concentration of neutralizing drugs, generated SARS-CoV-2 mutants escaping wild-type ACE2 decoy and monoclonal antibodies, whereas no escape mutant emerged against the engineered ACE2 decoy. Furthermore, inhalation of aerosolized decoys improved the outcomes of rodents infected with SARS-CoV-2 at a 20-fold lower dose than that of intravenous administration. Last, the engineered ACE2 decoy exhibited therapeutic efficacy for cynomolgus macaques infected with SARS-CoV-2. These results indicate that this engineered ACE2 decoy represents a promising therapeutic strategy to overcome immune-evading SARS-CoV-2 variants and that liquid aerosol inhalation could be considered as a noninvasive approach to enhance the efficacy of COVID-19 treatments.

[Subdural hematoma with reversible cerebral vasoconstriction syndrome: a case report].

A 71-year-old man had persistent cervical pain secondary to thunderclap headache during sleep. MRI conducted the next morning revealed subdural hematoma and convexity subdural hemorrhage on the right occipital region, and the patient was hospitalized. MRA showed vascular narrowing in the bilateral PCA. Follow-up MRA on day 8 of admission showed aggravated vascular narrowing of PCA, indicative of reversible cerebral vasoconstriction syndrome (RCVS). The patient was treated with a calcium-channel antagonist. Post-discharge MRA showed improvement of PCA narrowing, and the diagnosis of RCVS was confirmed.

Iodinated Contrast Media Substitution to Prevent Recurrent Hypersensitivity Reactions: A Systematic Review and Meta-Analysis.

Background Changing iodinated contrast media (ICM) may reduce the risk of recurrent ICM-induced hypersensitivity reactions in patients with a prior reaction. Purpose To perform a systematic review on the effectiveness of ICM change in comparison with no change to prevent recurrent ICM immediate hypersensitivity reactions. Materials and methods Multiple data bases were searched without language restriction between January 1990 and August 2021 to identify comparative studies of any design that included patients with a prior ICM hypersensitivity reaction to low-osmolality ICM and re-exposure to intravascular ICM. The methods used included a duplicate assessment of eligibility, double extraction of quantitative data, validity assessment, and random-effects meta-analysis. The primary outcome was the incidence of all-grade immediate recurrent hypersensitivity reactions. Secondary outcomes were the incidence of severe immediate recurrent hypersensitivity reactions and other adverse events associated with ICM change. Results Six retrospective observational studies at moderate to severe risk of bias assessed 7155 adult patients (4329 in the ICM change group and 2826 in the no-change group). Studies adopted nonstandardized switching methods, and the proportions of the ICM change group ranged between 19% (five of 27 examinations) and 80% (3104 of 3880 examinations). A Bayesian meta-analysis revealed that changing ICM was associated with a reduced risk of recurrent hypersensitivity reaction by 61% (risk ratio = 0.39; 95% credible interval [CrI]: 0.24, 0.58). The wide-ranging estimates of risk reduction were not explained by the risk of bias ratings, the event rates in the no-change group, the index-reaction severity, or the co-administered nonstandard premedication. Rare severe recurrent reactions (five studies with five events) precluded a conclusion (risk ratio = 0.34, favoring ICM change; CrI: 0.01, 3.74). Adverse events associated with ICM change were not reported. Conclusion In observational evidence of limited quality, iodinated contrast media (ICM)-change was associated with a reduced risk of recurrent immediate hypersensitivity reaction in patients with a prior ICM-induced hypersensitivity reaction. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by McDonald in this issue.

Th17 Cells Participate in Thy1.1 Glomerulonephritis Which Is Ameliorated by Tacrolimus.

INTRODUCTION: Thy1.1 glomerulonephritis (Thy1.1 GN) in rats is widely used as an experimental model of mesangial proliferative glomerulonephritis (GN). We previously reported that T-helper (Th) cells were accumulated in glomeruli from the early phase of this model and that not Th2 cells but Th1 cells play an important role in the development of glomerular alterations. Although Th17 is reported to be involved in the pathogenesis of several autoimmune diseases, the role of Th17 cells in the pathogenesis of mesangial alterations in Thy1.1 GN remains unclear. METHODS: The kinetics of the infiltration of subsets of Th cells and the expression of IL-17 in Thy1.1 GN were analyzed. Next, the localization and the cell types of IL-17 receptor (IL-17R)-positive cells and IL-6-positive cells were analyzed. Then, the effect of tacrolimus on the expressions of Th17-related cytokines in Thy1.1 GN was analyzed. RESULTS: Not only Th1 cells but also Th17 cells were recruited into glomeruli from the early phase of the disease. mRNA expression of IL-17 in glomeruli was elevated. The increased positive expression of IL-17R was detected in the mesangial area, and some of IL-17R-positive cells were co-stained with IL-6. Tacrolimus treatment ameliorated mesangial alterations by suppressing the expressions of Th17-related cytokines such as IL-17 and IL-6. CONCLUSION: Th17 cells participate in the development of Thy1.1 GN, a mimic of mesangial proliferative GN, and Th17 cells and their related cytokines are pertinent therapeutic targets.

Establishment of monoclonal antibodies broadly neutralize infection of hepatitis B virus.

Antibodies against hepatitis B virus S protein can protect against hepatitis B virus (HBV) infection. Therefore, hepatitis B immunoglobulin (HBIG), which contains HBsAb, is used clinically as a therapy for HBV infection. In this study, a series of monoclonal antibodies that recognize multiple HBV genotypes was obtained. All the antibodies recognized conformational epitopes of S protein, but not linear epitopes. Several antibodies neutralized HBV infection and exhibited strong affinities and neutralizing activities. Antigenic epitope analysis demonstrated that they recognized residue Ile152 of S protein, which is localized outside the "a" determinant. Ile152 is highly conserved, and a mutation in this residue resulted in reduced expression of large hepatitis B surface proteins (L protein), suggesting that the amino acid at this position is involved in the expression of L protein. In addition, the antibodies neutralized the infection of hepatitis D virus possessing a Gly145 mutation to Arg in S protein, which is a well-known escape mutation against HBIG treatment. Using mouse monoclonal antibodies, a humanized antibody possessing affinities and neutralizing activities similar to those of the original mouse antibody was successfully established. The antibodies generated in this study may have the potential for use in alternative antibody therapies for HBV infection.

Massive hemothorax in a pregnant patient with neurofibromatosis type 1.

BACKGROUND: Reports of spontaneous hemothorax in patients with neurofibromatosis type 1 are scarce despite the severe complication. We herein present the first case of hemothorax in a neurofibromatosis type 1 patient during pregnancy and discuss the difficulty associated with its diagnosis and treatment. CASE PRESENTATION: A 39-year-old female at 34 weeks gestation presented with sudden left back pain and dyspnea. Chest radiography revealed massive left pleural effusion. Computed tomography showed bleeding from the intercostal artery. Although the patient appeared hemodynamically stable, the fetus was in a critical condition. Emergency caesarean section was performed within 1 hour. Subsequently, we performed endovascular coil embolization of the intercostal artery. While this intensive treatment saved the patient, her fetus could not be rescued. CONCLUSIONS: Patients with neurofibromatosis type 1 may develop massive hemothorax without gross lesions. In late pregnancy, sufficient infusion and quick hemostasis are essential and can be lifesaving.

Anemia Prevalence and Anthropometric Status of Indigenous Women and Young Children in Rural Botswana: The San People.

In Botswana, there is limited data available on the health and nutritional status of the San People (also known as the Basarwa or Bushmen), an Indigenous minority group primarily living in the Ghanzi District. Our aim in this study was to assess anemia prevalence among and anthropometric indices of women and young children in Ghanzi District through a cross-sectional survey. We recruited 367 mother-child pairs (women 15-49 years and children 6-59 months) in nine randomly selected areas. A capillary blood sample was collected, and weight and height were measured. Hemoglobin (Hb) concentration was measured with use of a hemoglobinometer (HemoCue, AB), as per global recommendations. Overall, adjusted anemia prevalence was 12% in non-pregnant women (Hb < 120 g/L), 26% in pregnant women (Hb < 110 g/L), and 42% in children (Hb < 110 g/L), but it varied widely depending on whether or not the controversial factor of ethnicity was adjusted for (range of 6-26%, 22-30%, and 35-68% prevalence, respectively). Thirty-nine percent (n = 133/344) of non-pregnant women and 52% (n = 12/23) of pregnant women were underweight (BMI < 18.5 kg/m2). In children aged 6-23 months, 41% were underweight (weight-for-age z-score < -2 SD), 13% were wasted (weight-for-height z-score < -2 SD), and 65% were stunted (height-for-age z-score < -2 SD); in children aged 24-59 months, 57% were underweight, 13% were wasted, and 66% were stunted. Fifty-six percent (n = 205/367) of women self-reported smoking in any form (rolled cigarettes or snuffing). The high prevalence of smoking among women, underweight status among pregnant women, and anemia, stunting, and wasting among children is of the highest concern for public health and should be addressed in future health and nutrition programming.

Neurosurgical Pathology and Management of Limited Dorsal Myeloschisis Associated with Congenital Dermal Sinus in Infancy.

BACKGROUND: Because of the shared origin of limited dorsal myeloschisis (LDM) and congenital dermal sinus (CDS), CDS elements may be found within the fibroneural LDM stalk. When part of the CDS invested in the intradural stalk is left during untethering surgery, inclusion tumors such as dermoid cysts may develop. However, the most appropriate surgical strategy for LDM with CDS is still under debate. METHODS: Of 19 patients with LDM, 3 (15.8%) had histologically verified CDS elements. We retrospectively analyzed the clinicopathological findings of these patients. RESULTS: In patient 1, the entire stalk including a tiny dermoid cyst at the intradural stalk could be resected through two-level laminectomy during untethering at 6 months of age. In patients 2 and 3, the stalk appeared to be a typical LDM stalk during the initial surgery at 18 and 7 days, respectively; however, CDS was histologically diagnosed in the proximal severed end of the stalk. Postoperative three-dimensional heavily T2-weighted imaging demonstrated spherical enlargement of the remnant stalk, and the entire length of the remnant stalk including newly developed dermoid was resected during the second surgery at 3 years 11 months and 11 months, respectively. Histopathologically, glial fibrillary acidic protein-immunopositive neuroglial tissues and CDS elements were mainly located at the proximal and distal sites of the stalk, respectively, supporting the "dragging down and pulling up" theory. In patients 2 and 3, however, the proximal head of the dermoid cyst passed the distal head of the neuroglial tissues and located at the stalk-cord attachment. CONCLUSION: Surgeons should be aware of the approximately 10% possibility of the coexistence of CDS when managing infant LDM. However, the recommendation for excision of the entire length of the LDM stalk in all patients should be more carefully made because such a strategy may result in an unnecessary extent of laminotomy/laminectomy for most patients with pure LDM. However, once the postoperative histological examination reveals coexistence of CDS in the resected proximal part of the stalk, the entire length of the remnant stalk should be excised as soon as possible.

Pharmacologic and non-pharmacologic interventions to prevent hypersensitivity reactions of non-ionic iodinated contrast media: a systematic review protocol.

INTRODUCTION: Iodinated contrast media are commonly used in medical imaging and can cause hypersensitivity reactions, including rare but severe life-threatening reactions. Although several prophylactic approaches have been proposed for severe reactions, their effects remain unclear. Therefore, we aim to review systematically the preventive effects of pharmacologic and non-pharmacologic interventions and predictors of acute, hypersensitivity reactions. METHODS AND ANALYSIS: We will search the PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases from 1 January 1990 through 31 December 2019 and will examine the bibliographies of eligible studies, pertinent review articles and clinical practice guidelines. We will include prospective and retrospective studies of any design that evaluated the effects of pharmacological and non-pharmacological preventive interventions for adverse reactions of non-ionic iodinated contrast media. Two assessors will independently extract the characteristics of the study and intervention and the quantitative results. Two independent reviewers will assess the risk of bias using standard design-specific validity assessment tools. The primary outcome will be reduction in acute contrast media-induced hypersensitivity reactions. The secondary outcomes will include characteristics associated with the development of contrast media-induced acute hypersensitivity reactions, and adverse events associated with specific preventive interventions. Unique premedication regimens (eg, dose, drug and duration) and non-pharmacological strategies will be analysed separately. Average-risk and high-risk patients will be considered separately. A meta-analysis will be performed if appropriate. ETHICS AND DISSEMINATION: Ethics approval is not applicable, as this will be a secondary analysis of publicly available data. The results of the analysis will be submitted for publication in a peer reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019134003.

Socialization Practices Regarding Shame in Japanese Caregiver-Child Interactions.

Affect is both an organizing force and a product of socialization practices in communities. Shame is an affective experience that is primarily rooted in socially shared normativity, and it has featured in studies of language socialization that examine how children are socialized into their socio-culturally structured universe (Duranti et al., 2012). After the publication of Benedict's (1946) seminal work, shame became associated with the ethos of East Asian cultures. Inspired by previous work, this paper focuses on the use, in socialization, of phrases that include the Japanese term hazukashii, which is commonly translated as shameful, in the context of Japanese caregiver-child interactions. We videotaped interactions between young Japanese children and their caregivers in natural settings and examined the gestures and speech around uses of hazukashii. The results indicate that phrases including hazukashii are often used when a child hesitates to perform an appropriate action or performs an act that is deemed inappropriate. The caregiver thereby provides an account that the action is understandable in the given context. Further, hazukashii is also used in teasing contexts. This is done to promote a cooperative and pleasant atmosphere. The word hazukashii is a powerful tool for the language socialization of children in Japanese speech communities.

Validity of a disposable catheter to drain urine overnight in neurogenic bladder.

BACKGROUND: Overnight catheter drainage (OCD) is introduced to avoid overdistention of the bladder at night-time when clean intermittent catheterization proves ineffective for daytime management of neurogenic bladder. We adopted OCD using disposable silicone no-balloon (DSnB) catheters, with the distal end outside the body opening into diapers. OCD using DSnB catheter, however, had risks of retrograde bacterial contamination. Therefore, in this study, the validity of equipping DSnB catheters with check valves to prevent retrograde bacterial contamination was examined. METHODS: For the in vitro study, excised saline-filled swine bladders were drained using DSnB catheters with or without check valves, and the time required for intravesical pressure to reach 5 cmH2 O was measured. For the in vivo study, in cross-over experiments comparing DSnB catheters with and without check valves, OCD using DSnB catheters for 10 h was performed in rabbits under analgesia. Bacterial growth from urine samples before and after OCD and residual urine volume were examined. RESULTS: For the in vitro experiment, the median drainage time was 368.2 s (range, 88-1,085 s) and 344.7 s (range, 28-840 s) with and without check valves, respectively (n = 6), which was not significantly different. For the in vivo experiment, in cross-over experiments (n = 8) new bacterial growth rates after OCD did not differ, and median residual urine volume was 17.1 mL (range, 0-75 mL) and 1.2 mL (range, 0-5 mL) with and without check valves, respectively (P = 0.055). CONCLUSIONS: Installing a check valve in the DSnB catheter did not decrease new bacterial growth, while tending to increase residual urine volume. DSnB catheters without check valves appear to be better for continuous drainage of urine from bladder.

Bringing the Real World Into Developmental Science: A Commentary on Weber, Fernald, and Diop (2017).

This article examines the parent intervention program evaluated by Weber et al. (2017) and argues that there are scientific and ethical problems with such intervention efforts in applied developmental science. Scientifically, these programs rely on data from a small and narrow sample of the world's population; assume the existence of fixed developmental pathways; and pit scientific knowledge against indigenous knowledge. The authors question the critical role of talk as solely providing the rich cognitive stimulation important to school success, and the critical role of primary caregivers as teachers of children's verbal competency. Ethically, these programs do not sufficiently explore how an intervention in one aspect of child care will affect the community's culturally organized patterns of child care.

Molecular dynamics study of tridymite.

Structural changes in tridymite have been investigated by molecular dynamics simulation. Two thermal processes were carried out, one cooling from the high-temperature hexagonal structure of tridymite (HP-tridymite) and the other heating from the low-temperature monoclinic structure of tridymite (MX1-tridymite). The former process showed that HP, LHP (low-temperature hexagonal structure), OC (orthorhombic structure with C2221 symmetry) and OP (orthorhombic structure with P212121 symmetry)-like structures appeared in sequence. In contrast, the latter process showed that MX1, OP, OC, LHP and HP-like structures appeared in sequence. Detailed analysis of the calculated structures showed that the configuration underwent stepwise changes associated with several characteristic modes. First, the structure of HP-tridymite determined from diffraction experiments was identified as a time-averaged structure in a similar manner to ß-cristobalite, thus indicating the important role of floppy modes of oxygen atoms at high temperature - one of the common features observed in silica crystals and glass. Secondly, the main structural changes were ascribed to a combination of distortion of the six-membered rings in the layers and misalignment between layers. We suggest that the slowing down of floppy oxygen movement invokes the multistage emergence of structures with lower symmetry on cooling. This study therefore not only reproduces the sequence of the main polymorphic transitions in tridymite, except for the appearance of the monoclinic phase, but also explains the microscopic dynamic structural changes in detail.

Successful Management of Fulminant Guillain-Barré Syndrome and Its Complications.

A 3-year-old girl presented with muscle weakness of her limbs and trunk 6 days after developing symptoms of common cold. Two days later, she experienced respiratory arrest with a Glasgow Coma Scale score of 3, necessitating endotracheal intubation. Therefore, she was transferred to our hospital with suspected acute encephalopathy. Although no abnormalities were observed on brain and spinal magnetic resonance imaging and electroencephalography, peripheral nerve conduction velocity tests failed to evoke motor and sensory nerve action potentials. Thus, we gave a diagnosis of fulminant Guillain-Barré syndrome and initiated immunoglobulin therapy. On day 3 of admission, she developed sinus tachycardia that induced circulatory failure and oliguria, which was successfully treated with landiolol. Subsequently, we performed plasmapheresis followed by immunoglobulin and steroid pulse therapies. She was weaned off the mechanical ventilator by day 20 of admission, was ambulatory by day 44, and had completely recovered without any adverse sequelae by day 55. In conclusion, landiolol was effective for treating acute sinus tachycardia-induced circulatory failure and played a key role in saving the life of this patient.

Partition Function and Configurational Entropy in Non-Equilibrium States: A New Theoretical Model.

A new model of non-equilibrium thermodynamic states has been investigated on the basis of the fact that all thermodynamic variables can be derived from partition functions. We have thus attempted to define partition functions for non-equilibrium conditions by introducing the concept of pseudo-temperature distributions. These pseudo-temperatures are configurational in origin and distinct from kinetic (phonon) temperatures because they refer to the particular fragments of the system with specific energies. This definition allows thermodynamic states to be described either for equilibrium or non-equilibrium conditions. In addition; a new formulation of an extended canonical partition function; internal energy and entropy are derived from this new temperature definition. With this new model; computational experiments are performed on simple non-interacting systems to investigate cooling and two distinct relaxational effects in terms of the time profiles of the partition function; internal energy and configurational entropy.

Culture and emotion perception: comparing Canadian and Japanese children's and parents' context sensitivity.

Prior research on the perception of facial expressions suggests that East Asians are more likely than North Americans to incorporate the expressions of background figures into their judgment of a central figure's emotion (Masuda et al. in J Pers Soc Psychol 94:365-381, 2008b). However, little research has examined this issue in the context of developmental science, especially during joint sessions where parents engage in a task in front of their 7-8-year-old children. In this study, 22 Canadian and 20 Japanese child-parent dyads participated in an emotion judgment task, and were asked to judge a central figure's emotion and explain their reasoning. The results indicated that while early elementary school children did not show culturally dominant reasoning styles, parents displayed culturally dominant modes of attention, serving as models for their children.

The Communication of Culturally Dominant Modes of Attention from Parents to Children: A Comparison of Canadian and Japanese Parent-Child Conversations during a Joint Scene Description Task.

Previous findings have indicated that, when presented with visual information, North American undergraduate students selectively attend to focal objects, whereas East Asian undergraduate students are more sensitive to background information. However, little is known about how these differences are driven by culture and socialization processes. In this study, two experiments investigated how young children and their parents used culturally unique modes of attention (selective vs. context sensitive attention). We expected that children would slowly learn culturally unique modes of attention, and the experience of communicating with their parents would aid the development of such modes of attention. Study 1 tested children's solitary performance by examining Canadian and Japanese children's (4-6 vs. 7-9 years old) modes of attention during a scene description task, whereby children watched short animations by themselves and then described their observations. The results confirmed that children did not demonstrate significant cross-cultural differences in attention during the scene description task while working independently, although results did show rudimentary signs of culturally unique modes of attention in this task scenario by age 9. Study 2 examined parent-child (4-6 and 7-9 years old) dyads using the same task. The results indicated that parents communicated to their children differently across cultures, replicating attentional differences among undergraduate students in previous cross-cultural studies. Study 2 also demonstrated that children's culturally unique description styles increased significantly with age. The descriptions made by the older group (7-9 years old) showed significant cross-cultural variances in attention, while descriptions among the younger group (4-6 years old) did not. The significance of parental roles in the development of culturally unique modes of attention is discussed in addition to other possible facilitators of this developmental process.

Ability of a novel system for neonatal extracorporeal renal replacement therapy with an ultra-small volume circuit to remove solutes in vitro.

BACKGROUND: We automated our manual, syringe-driven extracorporeal renal replacement therapy (eRRT) system with an ultra-small volume circuit (3.2 ml) that is suitable for neonates without blood priming. Our objective was to determine the solute clearance and water balance of the automated and manual systems in vitro. METHODS: Stored whole blood samples containing exogenous urea, creatinine (Cr), potassium (K), and ammonia (NH3) to imitate acute kidney injury (AKI) and hyperammonemia were dialyzed for 3 h (blood flow, 4.0 ml/min; dialysate flow, 600 ml/h) with a continuous infusion of heparin. Solute clearance and sample weight were then compared with values before dialysis. RESULTS: The median clearance of blood urea nitrogen, Cr, K, and NH3 ranged from 1.7 to 2.3 and from 2.4 to 2.6 ml/min, and the median weight of the samples was decreased by 3.8 g and increased by 8.3 g after 3 h of dialysis using the manual and automated systems, respectively. CONCLUSIONS: The automated system effectively cleared solutes, but safety concerns were associated with platelet consumption and fluid balance. Additional studies are needed to establish the safety and accuracy of this novel system for clinical use in neonates and preterm infants.