Etiologic Classification Criteria of ARCO on Femoral Head Osteonecrosis Part 2: Alcohol-Associated Osteonecrosis

Background

Although alcohol is a leading risk factor for osteonecrosis of the femoral head (ONFH) and its prevalence reportedly ranges from 20% to 45%, there are no unified classification criteria for this subpopulation. In 2015, Association Research Circulation Osseous decided to develop classification criteria for alcohol-associated ONFH.

Optimal parameter selection problem with application to the synchronization of delivery cycles in a supply chain with Wiener process

In this paper, we use optimal parameter selection technique to develop two models involving single‐vendor–multiple‐buyer supply chain, which are called the dynamic independent optimization (DIO) model and the dynamic synchronized cycles (DSC) model, respectively. These models are, respectively, similar to the traditional static independent policy model and the traditional static synchronized cycle model, except that the deterministic demands of the buyers in the above two static models are now being replaced by the stochastic demands satisfying a Wiener process, which have more real‐life applications. Similar to the above static synchronized cycles model, the synchronization of the supply chain in our DSC model is also achieved by scheduling the delivery days of the buyers and coordinating them with the vendor's production cycle. Finding the optimal expected system costs of the DIO model and the DSC model involves solving optimal parameter selection problems governed by ordinary differential equations, whose final times are continuous decision variables and discrete decision variables, respectively. Computational methods have been developed for solving these problems. Numerical results show that the coordinated policy is better than the independent optimization policy, in terms of minimizing the expected system cost of the entire supply chain. Sensitivity analysis is performed to test the effect of changing the cost coefficients and the value on the performances of these models, where is the ratio of the total mean demand rate of all the buyers over the vendor's production rate.     

Melatonin safeguards against fatty liver by antagonizing TRAFs‐mediated ASK1 deubiquitination and stabilization in a β‐arrestin‐1 dependent manner

Melatonin has been previously shown to prevent nonalcoholic fatty liver disease (NAFLD), yet the underlying mechanisms are poorly understood. Here, we identified a previously unknown regulatory action of melatonin on apoptosis signal‐regulating kinase 1 (ASK1) signaling pathway in the pathogenesis and development of NAFLD. Although melatonin administration did not alter food intake, it significantly alleviated fatty liver phenotypes, including the body weight gain, insulin resistance, hepatic lipid accumulation, steatohepatitis, and fibrosis in a high‐fat diet (HFD)‐induced NAFLD mouse model (in vivo). The protection of melatonin against NAFLD was not affected by inactivation of Kupffer cell in this model. In NAFLD mice liver, ASK1 signal cascade was substantially activated, evidence by the enhancement of total ASK1, phospho‐ASK1, phospho‐MKK3/6, phospho‐p38, phospho‐MKK4/7, and phospho‐JNK. Melatonin treatment significantly suppressed the ASK1 upregulation and the phosphorylation of ASK1, MKK3/6, MKK4/7, p38, and JNK. Mechanistically, we found that lipid stress triggered the interaction between ASK1 and TNF receptor‐associated factors (TRAFs), including TRAF1, TRAF2, and TRAF6, which resulted in ASK1 deubiquitination and thereby increased ASK1 protein stability. Melatonin did not alter ASK1 mRNA level; however, it activated a scaffold protein β‐arrestin‐1 and enabled it to bind to ASK1, which antagonized the TRAFs‐mediated ASK1 deubiquitination, and thus reduced ASK1 protein stability. Consistent with these findings, knockout of β‐arrestin‐1 in mice partly abolished the protection of melatonin against NAFLD. Taken together, our results for the first time demonstrate that melatonin safeguards against NAFLD by eliminating ASK1 activation via inhibiting TRAFs‐mediated ASK1 deubiquitination and stabilization in a β‐arrestin‐1 dependent manner.     

Systemic disruption of the homeostasis of transfer RNA isopentenyltransferase causes growth and development abnormalities in Bombyx mori

Isopentenylation at A37 (i⁶A37) of some transfer RNAs (tRNAs) plays a vital role in regulating the efficiency and fidelity of protein synthesis. However, whether insects, which are well known for their highly efficient protein synthesis machinery, employ this regulatory mechanism remains uninvestigated. In the current study, a candidate tRNA isopentenyltransferase (IPT) gene with three alternative splicing isoforms (BmIPT1–BmIPT3) was identified in Bombyx mori (silkworm). Only BmIPT1 could complement a yeast mutant lacking tRNA IPT. Phylogenetic analysis showed that silkworm tRNA IPT is conserved in the Lepidoptera. BmIPT was expressed in all B. mori tissues and organs that were investigated, but was expressed at a significantly higher level in silk glands of the fourth instar compared to the first day of the fifth instar. Interestingly, BmIPT was expressed at a significantly higher level in the domesticated silkworm, B. mori, than in wild Bombyx mandarina in multiple tissues and organs. Knock‐down of BmIPT by RNA interference caused severe abnormalities in silk spinning and metamorphosis. Constitutive overexpression of BmIPT1 using a cytoplasmic actin 4 promoter in B. mori raised its messenger RNA level more than sixfold compared with nontransgenic insects and led to significant decreases in the body weight and cocoon shell ratio. Together, these results confirm the first functional tRNA IPT in insects and show that a suitable expression level of tRNA IPT is vital for silk spinning, normal growth, and metamorphosis. Thus, i⁶A modification at position A37 in tRNA probably plays an important role in B. mori protein synthesis.     

Retrospective analysis of forensic cases in refugees admitted to emergency department

IntroductionThe aim of this study was to compare the distribution and frequency of forensic medical events in a refugee group with that of the general population, and thus, extrapolate the problems encountered in the immigrant population.MethodsThose cases admitted to the emergency department (ED) for any reason that required a forensic examination between January 2016 and June 2018 were investigated retrospectively.ResultsA total of 310 refugees were admitted to the ED for forensic medical events. The most common nations of origin of the refugees were Iraq (n = 167), Syria (n = 65), and Afghanistan (n = 28). The median age of the refugees was 24 years old (interquartile range = 17–33). With regard to forensics, the most common reasons for the refugees to present to the ED were motor vehicle accidents 27.4%, assaults 25.8%, employment and industrial accidents 16.1%, and suicide attempts 10.3%. Other than suicide attempts, all of the forensic presentations were more common in the males. The outcomes of the refugee group were as follows: 92.3% were discharged, 5.8% were admitted to the hospital, 1% were admitted to the intensive care unit (ICU), and 1% were transferred. Suicide attempts were the most common reasons for the ICU admissions, while the most common reasons for the hospital admissions were orthopedic injuries.ConclusionIn general, the forensic event frequency in the refugee group was lower (p = 0.001); however, this was a single center study, and there could have been unrecorded cases due to an inability to access healthcare assistance, so these results may not be reliable.     

Recent trends in the prevalence of Helicobacter Pylori in symptomatic children: A 12-year retrospective study in a tertiary centre

Objective

Helicobacter pylori infection is common among Asians. However, evidence in the recent years has demonstrated a decrease in the prevalence of H. pylori infection among children and adults worldwide. Our aim was to update its prevalence in symptomatic children in our locality in the recent 12?years and compared to the results of our previous review published in 2005.

Fertility Outcome After Renal Transplantation: A Single-Center Experience

BackgroundWomen suffering from kidney disease are more prone to fertility problems, due to uremia. Fortunately, their fertility rate increases dramatically after renal transplantation. This study analyzes the predictors/risk factors of successful pregnancy with live birth outcome while presenting an overview of the 7-year experience of a single center.MethodsThis retrospective cohort study includes 239 women of reproductive age (18–40 years) who underwent renal transplantation in a tertiary Turkish clinic between October 1, 2011, and August 24, 2017. The subjects were invited to take part in a survey questioning their obstetric characteristics and they were assessed in 2 groups: fertile and infertile. Multivariable linear regression analysis was conducted to determine the predictors of a successful pregnancy.ResultsThirty-five 35 patients wished to become pregnant: 12 got pregnant spontaneously, while 21 failed to become pregnant (spontaneously). The mean age of the patients at the survey was 34 ± 7. Regular menstrual cycles after renal transplantation, tacrolimus-mycophenolate mofetil maintenance protocol, and age at transplantation were found to be predictors of spontaneous pregnancy. The duration of peritoneal dialysis was significantly longer in the infertile group (48 vs 12 months).ConclusionEnd-stage renal disease's negative impacts, including menstrual abnormality and fertility problems, can be overcome by successful kidney transplantation with appropriate immunosuppression. Minimizing the duration of peritoneal dialysis, particularly in patients who desire future fertility, may be accepted as a logical management strategy.