Insulin Autoimmune Syndrome: A Case Report Highlighting Diagnostic Pitfalls.

Insulin autoimmune syndrome (IAS) is characterized by spontaneous hyperinsulinemic hypoglycemia and the presence of insulin autoantibodies in high titers without exogenous insulin use. The C-peptide level during a hypoglycemia episode is useful for differentiating spontaneous hypoglycemia. Generally, low C-peptides are suspicious for exogenous insulin administration. We report a 47-year-old male nurse who presented with an initial episode of hypoglycemia. Despite the pattern of hyperinsulinemic hypoglycemia and low C-peptide, he was diagnosed with IAS based on the presence of insulin autoantibodies. This case underscores the importance of suspecting IAS in non-diabetic adults with hypoglycemia, even in the setting of low C-peptide levels.

Lymphomatosis cerebri caused by adult T cell leukemia/lymphoma: a differential diagnosis for depression: a case report.

BACKGROUND: Primary central nervous system lymphoma is rare, and primary central nervous system T cell lymphoma is relatively uncommon, contributing to < 5% of all cases. Lymphomatosis cerebri, a rare subtype of primary central nervous system lymphoma, is characterized by extensive white-matter lesions on magnetic resonance imaging and nonspecific symptoms, such as cognitive decline and depression. Reports of lymphomatosis cerebri in adult T cell leukemia/lymphoma are limited. CASE PRESENTATION: A 49-year-old Japanese man gradually developed insomnia, anorexia, and weight loss over a 2-month period following work-related promotion. Initially diagnosed with depression, his condition rapidly deteriorated with cognitive decline and motor dysfunction. Despite various treatments, his symptoms persisted within a month. Upon admission, the presence of neurological abnormalities suggestive of a central nervous system disorder raised suspicion of a cerebral lesion. Diagnostic tests revealed extensive brain lesions on imaging and the presence of atypical lymphocytes (flower cells) in the cerebrospinal fluid. The patient was diagnosed with lymphomatosis cerebri due to adult T cell leukemia/lymphoma, a rare presentation in the literature. Due to irreversible brainstem damage and poor neurological prognosis, aggressive treatment was not initiated, and the patient died, with an autopsy confirming the diagnosis. CONCLUSION: Lymphomatosis cerebri with adult T cell leukemia/lymphoma is very rare. It is crucial to promptly consider lymphomatosis cerebri as a differential diagnosis, particularly in cases of rapid cognitive decline and poor treatment response. Recognition of lymphomatosis cerebri as an important differential diagnosis for cognitive decline, and depression is necessary for timely intervention and management. Further research is required to better understand this unique and rare presentation in adult T cell leukemia/lymphoma.

Three layers in spinal canal.

Contrast-enhanced computed tomography revealed spontaneous spinal epidural hematoma, which mimicked aortic dissection.

Purulent nasal discharge due to gonococcal nasopharyngitis in a neonate.

Neonatal gonorrhea, caused by Neisseria gonorrhoeae, is an uncommon but important disease to prevent because its complications, such as gonococcal ophthalmia neonatorum causes blindness if untreated. Neonatal gonococcal nasopharyngitis is a rare, but important clinical manifestation to suspect gonococcal infection in a neonate. Herein we report a case of neonatal gonococcal nasopharyngitis, presented with purulent nasal discharge. A full-term male neonate without perinatal complications developed purulent eye discharge on the 7th day of life. N. gonorrhoeae was isolated from the eye discharge culture; however, he did not receive the standard regimen. Subsequently, he presented to our hospital with fever and nasal discharge on the 20th day of life. N. gonorrhoeae was also isolated from nasal discharge and nasopharyngeal swabs without any evidence of chlamydia or syphilis. He received intravenous cefotaxime until disseminated gonococcal infection was ruled out and was discharged without any sequelae. Rhinorrhea in newborns requires consideration of mother-to-child transmission of various microorganisms, not only common respiratory viruses, but also rare, serious preventable infections such as gonorrhea or syphilis. Along with the recent syphilis patients on the rise in Japan, gonorrhea is an important disease to recognize, and the incidence could increase. Clinical manifestations of neonatal gonococcal infections, including nasopharyngitis, need to be recognized to suspect the diagnosis and initiate appropriate treatment to prevent serious complications.

Accuracy evaluation of the C. elegans cancer test (N-NOSE) using a new combined method.

Early cancer detection is critical for effective treatment. N-NOSE (Nematode-NOSE) is a simple, inexpensive, and highly sensitive cancer screening method based on the chemotaxis of the nematode Caenorhabditis elegans, which shows evasive action from the urine of healthy individuals while being attracted to the urine of cancer patients. Initially, N-NOSE relied on chemotaxis indexes obtained with 10-fold dilutions of urine samples. However, cancer tissue size and concentrations of cancer odors differ among cancer patients. In this study, we examined the accuracy improvement of N-NOSE method by using two types of dilutions, 10-fold and 100-fold. We have conducted N-NOSE tests with urine samples from 32 cancer patients (esophageal, gastric, colorectal, gallbladder, cholangiocarcinoma, breast, malignant lymphoma, and acute myeloid leukemia) along with 143 healthy subjects. Our data showed a significant difference in the N-NOSE at 10-fold dilution between the two groups (p < 0.0001), with an area under the ROC curve (AUC) of 0.9188 based on receiver operating characteristic (ROC) analysis. N-NOSE index at 100-fold dilutions was also significantly different between the two groups (p < 0.0001), with an AUC of 0.9032 based on ROC analysis. In this clinical study, we further improve N-NOSE with a combined method of two dilutions (10-fold and 100-fold) of urine samples, which results in a markedly improvement in cancer detection sensitivity of 87.5%. N-NOSE sensitivity improvement was significantly high even for early-stage cancer detection, which is in stark contrast with the sensitivity of detection using blood tumor markers (CEA, CA19-9 and CA15-3). These results strongly suggest that the N-NOSE test by this new combined method strikes a good balance between sensitivity and specificity.

Case Report: Analysis of Preserved Umbilical Cord Clarified X-Linked Anhidrotic Ectodermal Dysplasia With Immunodeficiency in Deceased, Undiagnosed Uncles.

Family history is one key in diagnosing inborn errors of immunity (IEI); however, disease status is difficult to determine in deceased relatives. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is one of the hyper IgM syndromes that is caused by a hypomorphic variant in the nuclear factor kappa beta essential modulator. We identified a novel IKBKG variant in a 7-month-old boy with pneumococcal rib osteomyelitis and later found that his mother has incontinentia pigmenti. Genetic analysis of preserved umbilical cords revealed the same variant in two of his deceased maternal uncles. Analysis of preserved umbilical cord tissue from deceased relatives can provide important information for diagnosing IEI in their descendants.

Laterality of toe grip strength in Kendo players.

[Purpose] The purpose of this study was to determine whether unilateral dominance exists in toe grip strength in Kendo players using a toe grip dynamometer. [Participants and Methods] In total, 15 male college Kendo players, who had no disability or pain in their feet, were included in the study. The participants completed a questionnaire to determine which foot the participants used as their front and rear foot while standing in Kendo. We measured toe grip strength three times on each side. We then extracted the maximum value of toe grip strength from the three measurements on each side and calculated the ratio of toe grip strength to body weight (%). [Results] All players used their right foot as the front foot. We found that the front foot toe grip strength was significantly stronger than the rear foot toe grip strength. [Conclusion] Our results suggest laterality of toe grip strength and the front foot toe grip strength is stronger than the rear foot toe grip strength in Kendo players.

Theoretical Study of Formation of Methanol under Hydrothermal Conditions.

We have examined the formation process of methanol by the reduction of formaldehyde under hydrothermal conditions. A formaldehyde absorbs a hydrogen molecule and turns to a methanol. Water molecules near a formaldehyde help to transfer protons to proceed the reduction process efficiently. The energy barrier for the reduction of a formaldehyde becomes 32.8 kcal/mol when a water cluster with five water molecules catalyzes the reduction. The ionic product becomes the largest under hydrothermal conditions. We introduce the acid-base catalytic effect due to hydronium and hydroxide on the reduction of formaldehyde. The energy barriers for the reduction of a formaldehyde are further reduced to 29.3 and 10.4 kcal/mol by the acid and base catalytic effects, respectively. The reduction of a formaldehyde is more effectively catalyzed by a hydroxide than a hydronium. The acid-base catalytic effect is not available at the high temperature of supercritical water due to the sudden decrease of the ionic product. It takes too long to form a reactant compound in supercritical water. The transition state theory is applied to calculate the reduction rate of a reactant compound, considering the tunneling effect of a proton. We confirmed that a metastable equilibrium state attains among single-carbon compounds except methanol and methane by reproducing the concentrations of the carbon compounds measured in a laboratory. We calculated the formation rate of methanol using the equilibrium concentration of formaldehyde. We compared the calculated formation rate with that determined by a laboratory experiment and confirmed that the present theoretical calculation is accurately able to describe the oxidative and reductive reaction network of single-carbon compounds under hydrothermal conditions. The present study can be applied to examine a reaction network of single-carbon compounds in hydrothermal vents on the Earth, Enceladus, and other solar system bodies such as Europa.

[Effect of adding X-ray examination to endoscopy in the assessment of the invasion depth of early gastric cancer].

In the assessment of invasion depth of early gastric cancer (EGC), the effect of adding X-ray examination to endoscopy was retrospectively investigated in 84 EGC lesions diagnosed at our hospital, including 62 differentiated and 22 undifferentiated lesions. Overall diagnostic accuracy was 75% with endoscopy and 82.1% when X-ray examination was performed in addition to endoscopy. This demonstrated an increase in the accuracy of 7.1% by adding X-ray examination. In terms of presence of ulceration, the additional effect of X-ray examination was higher for lesions without ulceration for both differentiated and undifferentiated lesions. In terms of tumor diameter, the additional effect of X-ray examination was higher for differentiated lesions of ≤30mm and for undifferentiated lesions of ≥21mm. In terms of tumor location, the additional effect of X-ray examination was higher for lesions located in the upper gastric corpus. Depending on the lesion, the addition of X-ray examination to endoscopy contributed to an increase in the accuracy of the assessment of the invasion depth of EGC.

Structure of the periplasmic domain of SflA involved in spatial regulation of the flagellar biogenesis of Vibrio reveals a TPR/SLR-like fold.

Bacteria have evolved various types of flagellum, an organella for bacterial motility, to adapt to their habitat environments. The number and the spatial arrangement of the flagellum are precisely controlled to optimize performance of each type of the flagellar system. Vibrio alginolyticus has a single sheathed flagellum at the cell pole for swimming. SflA is a regulator protein to prevent peritrichous formation of the sheathed flagellum, and consists of an N-terminal periplasmic region, a transmembrane helix, and a C-terminal cytoplasmic region. Whereas the cytoplasmic region has been characterized to be essential for inhibition of the peritrichous growth, the role of the N-terminal region is still unclear. We here determined the structure of the N-terminal periplasmic region of SflA (SflAN) at 1.9-Å resolution. The core of SflAN forms a domain-swapped dimer with tetratricopeptide repeat (TPR)/Sel1-like repeat (SLR) motif, which is often found in the domains responsible for protein-protein interaction in various proteins. The structural similarity and the following mutational analysis based on the structure suggest that SflA binds to unknown partner protein by SflAN and the binding signal is important for the precise control of the SflA function.

Rectal mucocele in the anterior wall of the rectum.

An 84-year-old man presented in 2009 with a sensation of discomfort in his anus, combined with difficulty in urination. He had previously undergone a haemorrhoidectomy in 1964. After examination, he was diagnosed with a rectal mucosal cyst and followed up for observation. In 2015, he presented to our hospital complaining that the cyst was prolapsing from his anus. CT revealed a 48×41 mm cystic mass in the anterior wall of the rectum. Tumour extirpation, via a transanal route, was performed. The postoperative pathological diagnosis confirmed a rectal mucocele. Rectal mucoceles are extremely rare, with no prior report of a mucocele in the anterior wall of the rectum. In this case, we believe the mucocele developed from an invagination of the mucous membrane or obstruction of the anal gland during suturing during the previous haemorrhoid surgery.

[A case of duodenal neuroendocrine carcinoma composed of small- and large-cell types].

A 78-year-old man underwent a detailed examination by upper gastrointestinal endoscopy for the complaint of epigastric pain. The examination revealed a hemicircumferential type 2 tumor in the descending duodenum. A subsequent biopsy led to a diagnosis of neuroendocrine carcinoma. Subtotal stomach-preserving pancreaticoduodenectomy was performed. The lesion was composed of small- and large-cell neuroendocrine carcinomas. The large-cell type component was positive for both caudal homeobox protein 2 and the cluster of differentiation 138, whereas the small-cell type component was negative for both. Our report may provide valuable information regarding the pathogenesis of neuroendocrine carcinoma.

Primary Formation Path of Formaldehyde in Hydrothermal Vents.

Formaldehyde is abundant in the universe and one of the fundamental molecules for life. Hydrothermal vents produce a substantial amount of hydrogen molecules by serpentinization and promote reductive reactions of single carbon compounds. The abundance of formaldehyde is expected to be low due to the high Gibbs free energy in hydrothermal vents. We consider two competing formation pathways of formaldehyde: (1) the reduction of CO by H2 and (2) the reduction of HCOOH by H2 to form a methanediol, followed by the dehydration of the methanediol. We performed a number of quantum chemical simulations to examine the formation of formaldehyde in the gas phase as well as in aqueous solution. The energy barrier is significantly reduced by the catalytic effect of water molecules in aqueous solution and becomes lowest when a water cluster consisted of 5 water molecules catalyzes the reduction. The energy barrier to form a methanediol by the reduction of HCOOH is lower by 17.5 kcal/mol than that to form a formaldehyde by the reduction of CO. Considering the low energy barrier to dehydrate methanediol, the primary pathway to form formaldehyde in hydrothermal vents is concluded to be the reduction of HCOOH by H2, followed by the dehydration of methanediol.

A case of synchronous quintuple gastric cancer with large-cell endocrine carcinoma.

The patient was a 73-year-old man who visited our department with black stools as the chief complaint. Upper digestive tract endoscopy revealed three type 2 lesions in the lesser curvature of the gastric antrum and the gastric angle and the posterior wall of the upper gastric body, which were diagnosed by biopsy as tub2, por, and sig, respectively. Total gastrectomy was performed. The final pathological diagnosis was quintuple gastric cancer with a main lesion of large-cell endocrine carcinoma and four adenocarcinoma sublesions. We report this extremely rare case of gastric endocrine cell carcinoma complicated by adenocarcinoma.

Localization and domain characterization of the SflA regulator of flagellar formation in Vibrio alginolyticus.

Many swimming bacteria use flagella as locomotive organelles. The spatial and numerical regulation of flagellar biosynthesis differs by bacterial species. The marine bacteria Vibrio alginolyticus use a single polar flagellum whose number is regulated positively by FlhF and negatively by FlhG. Cells lacking FlhF and FlhG have no flagellum. The motility defect in an flhFG deletion was suppressed by a mutation in the sflA gene that resulted in the production of multiple, peritrichous flagella. SflA is a Vibrio-specific protein. SlfA either facilitates flagellum growth at the cell pole or prevents flagellar formation on the cell body by an unknown mechanism. Fluorescent protein fusions to SflA localized to the cell pole in the presence of FlhF and FlhG, but exhibited both polar and lateral cell localization in ΔflhFG cells. Polar localization of SflA required the polar landmark protein HubP. Over-expression of the C-terminal region of SflA (SflAC ) in ΔflhFG ΔsflA cells suppressed the lateral flagellar formation. Our results suggest that SflA localizes with the flagella and that SflAC represses the flagellar initiation in ΔflhFG strains. A model is presented where SflA inhibits lateral flagellar formation to facilitate single polar flagellum assembly in V. alginolyticus cells.

A case of mixed adenoneuroendocrine carcinoma of the stomach.

A 71-year-old man who tested positive in a pepsinogen test also underwent upper gastrointestinal endoscopy. A 0-IIc lesion was identified at the posterior wall of the antrum. Biopsy findings indicated endocrine cell carcinoma. The patient underwent distal gastrectomy, and subsequent histopathological examination of the resected specimens showed a moderately differentiated adenocarcinoma (tub2) in the mucosa with transformation to small cell carcinoma in the submucosal and muscle layers. The final diagnosis was of a mixed adenoneuroendocrine carcinoma. We herein describe a case report of this patient with this rare form of gastric carcinoma.

Dehydration of Methanediol in Aqueous Solution: An ONIOM(QM/MM) Study.

We used ONIOM(QM/MM) method to examine the dehydration of a methanediol in aqueous solution. A methanediol and a small number of water molecules in the proximity of the methanediol are calculated with quantum mechanics (QM), while a number of water molecules far from the methanediol are calculated with molecular mechanics (MM). A molecular dynamical simulation shows that 12 water molecules are located within the hydration shell of a methanediol. The energy barrier for the dehydration of a methanediol decreases when we increase the number of water molecules in the QM region and converges toward a finite value when 12 water molecules are included in the QM region. This indicates a significant effect of water molecules within the hydration shell on the dehydration process of a methanediol in aqueous solution. The dehydration rate calculated with the ONIOM(QM/MM) method agrees well with that obtained from a laboratory experiment.