The Digestive Tract and Derived Primordia Differentiate by Following a Precise Timeline in Human Embryos Between Carnegie Stages 11 and 13

The precise mechanisms through which the digestive tract develops during the somite stage remain undefined. In this study, we examined the morphology and precise timeline of differentiation of digestive tract‐derived primordia in human somite‐stage embryos. We selected 37 human embryos at Carnegie Stage (CS) 11–CS13 (28–33 days after fertilization) and three‐dimensionally analyzed the morphology and positioning of the digestive tract and derived primordia in all samples, using images reconstructed from histological serial sections. The digestive tract was initially formed by a narrowing of the yolk sac, and then several derived primordia such as the pharynx, lung, stomach, liver, and dorsal pancreas primordia differentiated during CS12 (21–29 somites) and CS13 (≥ 30 somites). The differentiation of four pairs of pharyngeal pouches was complete in all CS13 embryos. The respiratory primordium was recognized in ≥ 26‐somite embryos and it flattened and then branched at CS13. The trachea formed and then elongated in ≥ 35‐somite embryos. The stomach adopted a spindle shape in all ≥ 34‐somite embryos, and the liver bud was recognized in ≥ 27‐somite embryos. The dorsal pancreas appeared as definitive buddings in all but three CS13 embryos, and around these buddings, the small intestine bent in ≥ 33‐somite embryos. In ≥ 35‐somite embryos, the small intestine rotated around the cranial‐caudal axis and had begun to form a primitive intestinal loop, which led to umbilical herniation. These data indicate that the digestive tract and derived primordia differentiate by following a precise timeline and exhibit limited individual variations. Anat Rec, 299:439–449, 2016. © 2016 Wiley Periodicals, Inc.     

Temporal association between sleep apnea–hypopnea and sleep bruxism events

There is some evidence suggesting that obstructive sleep apnea–hypopnea syndrome is concomitant with sleep bruxism. The aim of this study was to investigate the temporal association between sleep apnea–hypopnea events and sleep bruxism events. In an open observational study, data were gathered from 10 male subjects with confirmed obstructive sleep apnea–hypopnea syndrome and concomitant sleep bruxism. Polysomnography and audio‐video recordings were performed for 1 night in a sleep laboratory. Breathing, brain, heart and masticatory muscle activity signals were analysed to quantify sleep and sleep stage duration, and number and temporal distribution of apnea–hypopnea events and sleep bruxism events. Apnea–hypopnea events were collected within a 5‐min time window before and after sleep bruxism events, with the sleep bruxism events as the pivotal reference point. Two temporal patterns were analysed: (i) the interval between apnea–hypopnea events termination and sleep bruxism events onset, called T1; and (ii) the interval between sleep bruxism events termination and apnea–hypopnea events onset, called T2. Of the intervals between sleep bruxism events and the nearest apnea–hypopnea event, 80.5% were scored within 5 min. Most intervals were distributed within a period of <30 s, with peak at 0–10 s. The T1 interval had a mean length of 33.4 s and was significantly shorter than the T2 interval (64.0 s; P < 0.05). Significantly more sleep bruxism events were scored in association with the T1 than the T2 pattern (P < 0.05). Thus, in patients with concomitant obstructive sleep apnea–hypopnea syndrome and sleep bruxism, most sleep bruxism events occurred after sleep apnea–hypopnea events, suggesting that sleep bruxism events occurring close to sleep apnea–hypopnea events is a secondary form of sleep bruxism.     

Efficient induction of HIV-1 replication in latently infected cells through contact with CD4+ T cells: involvement of NF-kappaB activation

Reservoir cells latently infected with HIV-1 pose one of the major obstacles that hamper ultimate eradication of HIV-1 from infected patients. In this report, we showed that direct contact with MOLT-4 T cells induced HIV-1 replication in J(22)-HL-60 latently infected cells without any additional stimulus. Neutralization experiments revealed that pro-inflammatory cytokines, whose production was increased following cell-cell contact, were unlikely to be primarily involved in the induced HIV-1 replication. Cell-cell contact, but not soluble components in the culture supernatant, caused a rapid phosphorylation and degradation of IkappaBalpha, which led to elevated NF-kappaB DNA binding activity in J(22)-HL-60 cells. Furthermore, forced expression of a super-repressor form of IkappaBalpha or pretreatment with ritonavir efficiently blocked the activation of NF-kappaB and HIV-1 replication in J(22)-HL-60 cells co-cultured with MOLT-4 T cells. Moreover, either resting or PHA stimulated primary CD4(+) T cells induced HIV-1 replication in J(22)-HL-60 cells in a similar way with that of MOLT-4 cells. These results indicated that direct contact with CD4(+) T cells induced HIV-1 replication in latently infected cells and provide insight into the molecular mechanism of virus release from myeloid progenitor cells latently infected with HIV-1.     

Analysis of hypofibrinogenemias found on routine coagulation screening tests and identification of heterozygous dysfibrinogenemia or fibrinogen deficiency

We analyzed the clinical factors resulting in hypofibrinogenemia, which is defined as less than 100mg/dl of plasma fibrinogen values determined by a procedure based on the Thrombin-time method. Within a 12-month period, we assayed 5,746 patients (19,309 plasmas) and found 113 patients (1.97%) with hypofibrinogenemia. We categorized these patients as having decreased synthesis of fibrinogen (less than 3.0g/dl of albumin, 140 IU/l of Cholinesterase, and/or 50% on Hepaplastin Test), increased consumption of fibrinogen (more than 10 microg/ml of FDP D-dimer), known side effect of L-asparaginase administration, or other causes. Details are follows: 1) decreased synthesis: 26 patients, suspected of decreased synthesis (albumin: 3.1-3.4 g/dl): 4 patients, 2) increased consumption: 15 patients, suspected of increased consumption (FDP D-dimer: 5.0-9.9 g/dl): 1 case, 3) decreased synthesis combined with increased consumption: 24 patients, suspected of decreased synthesis and/or suspected of increased consumption: 14 patients, 4) side-effect of L-asparaginase administration: 24 patients, 5) heterozygous dysfibrinogenemia: 1 patient, 6) heterozygous fibrinogen deficiency: 1 patient, suspected of heterozygous fibrinogen deficiency: 1 patient, 7) unidentified: 2 patients with West syndrome treated with a combination of ACTH and valproic acid. Three patients with dysfibrinogenemia or fibrinogen deficiency showed normal or slightly prolonged PT values and normal APTT values. These data and our previous reports suggest that heterozygous patients with dysfibrinogenemia or fibrinogen deficiency do not demonstrate markedly prolonged PT and APTT values, differing from patients with afibrinogenemia.     

Orofacial granulomatosis of the lower lip and cheek: report of a case.

Orofacial granulomatosis (OFG) is a granulomatous disease of the orofacial region. This clinicopathological entity describes patients with oral lesions characterized by persistent and/or recurrent labial enlargement, ulcers, and a variety of other orofacial features, which on biopsy have lymphedema and noncaseating granulomas. The cause is idiopathic but appears to represent an abnormal immune reaction. This may be a manifestation of Crohn's disease (CD) since some patients with oral lesions develop typical bowel symptoms of CD in ensuing months to years; tooth-associated infections, sarcoidosis, food or contact allergies, and viruses have also been implicated in causing OFG. Clinical features of OFG are highly variable and sometimes so insidious that signs and symptoms are frequently not severe enough to cause alarm. The lips are most commonly involved and demonstrate a nontender, persistent swelling. Because of the relatively nonspecific clinical findings associated with granulomatous diseases, a microscopic diagnosis of granulomatous inflammation often presents a diagnostic dilemma for clinicians. We report a case of OFG of the lower lip and cheek and describe its management to add to the current body of literature on the subject.     

Tolvaptan Reduces Extracellular Fluid per Amount of Body Fluid Reduction Less Markedly than Conventional Diuretics

Objective Tolvaptan, a vasopressin V2 receptor antagonist, is a water diuretic, removing electrolyte-free water from the kidneys and affecting the water balance between the intracellular and extracellular fluid. We previously reported that tolvaptan efficiently reduced the intracellular fluid volume, suggesting its utility for treating cellular edema. Furthermore, tolvaptan is known for its low incidence of worsening the renal function, with conventional diuretics use associated with worsening of the renal function Methods In this retrospective observational study, five chronic kidney disease (CKD) patients with fluid retention were assessed by the bioelectrical impedance (BIA) method twice (before and after tolvaptan therapy). Tolvaptan was used with conventional diuretics. The post/pre ratio of extracellular water (ECW)/total body water (TBW) in the tolvaptan group was compared with that in 18 CKD patients undergoing body fluid reduction with conventional diuretics alone (conventional diuretics groups), taking the reduced amount of body fluid into consideration. Results Removing body fluid, either by tolvaptan or by conventional diuretics alone, decreased the ECW/TBW ratio. Of note, the reduction in extracellular fluid was milder in the tolvaptan group than in the conventional diuretics group. Conclusion Tolvaptan reduces the extracellular fluid per amount of body fluid reduction less markedly than conventional diuretics.     

Gene Expression Programming Model for Tribological Behavior of Novel SiC–ZrO2–Al Hybrid Composites

In order to improve product format quality and material flexibility, variety of application, and cost-effectiveness, SiC, ZrO₂, and Al hybrid composites were manufactured in the research utilizing the powder metallurgy (PM) technique. A model was created to predict the tribological behavior of SiC–ZrO₂–Al hybrid composites using statistical data analysis and gene expression programming (GEP) based on artificial intelligence. For the purpose of examining the impact of zirconia concentration, sliding distance, and applied stress on the wear behavior of hybrid composites, a comprehensive factor design of experiments was used. The developed GEP model was sufficiently robust to achieve extremely high accuracy in the prediction of the determine coefficient (R²), the root mean square error (RMSE), and the root relative square error (RRSE). The maximum state of the RMSE was 0.4357 for the GEP-1 (w1) model and the lowest state was 0.7591 for the GEP-4 (w1) model, while the maximum state of the RRSE was 0.4357 for the GEP-1 (w1) model and the minimum state was 0.3115 for the GEP-3 model (w1).     

Differential Genomics Output and Susceptibility of Iranian Patients with Unilocular Hydatidose

Background

The objective of this study was to investigate HLA-DRB1*and DQB1* allelic polymorphisms in Iranian patients with hydatidose. This is the first survey dealing with the correlation between HLA-DRB1* and DQB1* alleles and cystic echinococcosis in Iranian patients.

Methods

The study was carried out on 56 patients with confirmed cystic echinococcosis and 30 apparently healthy individuals living in Arak- Markazi Province by HLA-DRB1 and DQB1 typing through PCR-SSP method. The first step was to identify the patients and blood sampling. DNA was prepared from whole blood and PCR-SSP with 31 primer mixes for per sample was used. PCR reaction mixtures were loaded in agarose gels and bands were observed under UV illumination and gel document after electrophoresis. Analysis of results was carried out with specific softwares and frequency and interpretation tables for calculation of P-value in χ² test were provided via Fisher’s exact test. Significant samples were analyzed by logistic regression and odds-ratios were calculated.

Results

A statistically significant positive association was found between HLA-DQB1*03 and the resistance to cystic echinococcosis (P < 0.02) (odds-ratio = 2.87).

Conclusion

Immunogenetic susceptibility to unilocular hydatidose varies according to the HLA antigens in Arak, Markazi Province, and DQB1*03 molecules are associated with the level of immune response to parasite antigens.     

Differences in Macro‐ and Microarchitecture of the Appendicular Skeleton in Young Chinese and White Women

To identify the racial differences in macro‐ and microstructure of the distal radius and tibia that may account for the lower fracture rates in Asians than whites, we studied 61 healthy premenopausal Chinese and 111 white women 18–45 yr of age using high‐resolution pQCT (HR‐pQCT). The Chinese were shorter and leaner. Distal radius total cross‐sectional area (CSA) was 14.3% smaller in Chinese because of an 18.0% smaller trabecular area (p < 0.001). Cortical thickness was 8.8% greater in the Chinese, but cortical area was no different. Total volumetric BMD (vBMD) was 10.3% higher in the Chinese because of the 8.8% higher cortical thickness and 2.8% greater cortical density (all p < 0.01). Trabecular vBMD and bone volume/tissue volume (BV/TV) did not differ by race because trabeculae were 7.0% fewer but 10.8% thicker in Chinese than whites (both p < 0.01). Similar results were found at the distal tibia. Lower fracture risk in Chinese women may be partly caused by thicker cortices and trabeculae in a smaller bone‐more bone within the bone than in whites.     

Juvenile Paget's disease in an Iranian kindred with vitamin D deficiency and novel homozygous TNFRSF11B mutation

Juvenile Paget's disease (JPD) is a rare heritable osteopathy characterized biochemically by markedly increased serum alkaline phosphatase (ALP) activity emanating from generalized acceleration of skeletal turnover. Affected infants and children typically suffer bone pain and fractures and deformities, become deaf, and have macrocranium. Some who survive to young adult life develop blindness from retinopathy engendered by vascular microcalcification. Most cases of JPD are caused by osteoprotegerin (OPG) deficiency due to homozygous loss‐of‐function mutations within the TNFRSF11B gene that encodes OPG. We report a 3‐year‐old Iranian girl with JPD and craniosynostosis who had vitamin D deficiency in infancy. She presented with fractures during the first year‐of‐life followed by bone deformities, delayed development, failure‐to‐thrive, and pneumonias. At 1 year‐of‐age, biochemical studies of serum revealed marked hyperphosphatasemia together with low‐normal calcium and low inorganic phosphate and 25‐hydroxyvitamin D levels. Several family members in previous generations of this consanguineous kindred may also have had JPD and vitamin D deficiency. Mutation analysis showed homozygosity for a unique missense change (c.130T>C, p.Cys44Arg) in TNFRSF11B that would compromise the cysteine‐rich domain of OPG that binds receptor activator of NF‐κB ligand (RANKL). Both parents were heterozygous for this mutation. The patient's serum OPG level was extremely low and RANKL level markedly elevated. She responded well to rapid oral vitamin D repletion followed by pamidronate treatment given intravenously. Our patient is the first Iranian reported with JPD. Her novel mutation in TNFRSF11B plus vitamin D deficiency in infancy was associated with severe JPD uniquely complicated by craniosynostosis. Pamidronate treatment with vitamin D sufficiency can be effective therapy for the skeletal disease caused by the OPG deficiency form of JPD.