Fungal infections in solid organ transplantation: An update on diagnosis and treatment

Invasive fungal infections constitute an important cause of morbidity and mortality in solid organ transplantation recipients. Since solid organ transplantation is an effective therapy for many patients with end-stage organ failure, prevention and treatment of fungal infections are of vital importance. Diagnosis and management of these infections, however, remain difficult due to the variety of clinical symptoms in addition to the lack of accurate diagnostic methods. The use of fungal biomarkers can lead to an increased diagnostic accuracy, resulting in improved clinical outcomes. The evidence for optimal prophylactic approaches remains inconclusive, which results in considerable variation in the administration of prophylaxis. The implementation of a standard protocol for prophylaxis remains difficult as previous treatment regimens, which can alter the distribution of different pathogens, affect the outcome of antifungal susceptibility testing. Furthermore, the increasing use of antifungals also contributes to incremental costs and the risk of development of drug resistance. This review will highlight risk factors, clinical manifestations and timing of fungal infections and will focus predominately on the current evidence for diagnosis and management of fungal infections.     

Endovascular repair of acute traumatic injury of thoracic aorta

Blunt thoracic aortic injury is associated with a high mortality rate. It is the second leading cause of death after head injury from vehicle accidents. Surgical repair with graft interposition was the traditional treatment of blunt aortic injury however; the introduction of endovascular stent graft has revolutionized the definitive treatment of these injuries.     

Class IA phosphatidylinositol 3‐kinase regulates osteoclastic bone resorption through protein kinase B–mediated vesicle transport

Class IA phosphatidylinositol 3‐kinases (PI3Ks) are activated by growth factor receptors and regulate a wide range of cellular processes. In osteoclasts, they are activated downstream of α_vβ₃ integrin and colony‐stimulating factor‐1 receptor (c‐Fms), which are involved in the regulation of bone‐resorbing activity. The physiological relevance of the in vitro studies using PI3K inhibitors has been of limited value, because they inhibit all classes of PI3K. Here, we show that the osteoclast‐specific deletion of the p85 genes encoding the regulatory subunit of the class IA PI3K results in an osteopetrotic phenotype caused by a defect in the bone‐resorbing activity of osteoclasts. Class IA PI3K is required for the ruffled border formation and vesicular transport, but not for the formation of the sealing zone. p85α/β doubly deficient osteoclasts had a defect in macrophage colony‐stimulating factor (M‐CSF)–induced protein kinase B (Akt) activation and the introduction of constitutively active Akt recovered the bone‐resorbing activity. Thus, the class IA PI3K‐Akt pathway regulates the cellular machinery crucial for osteoclastic bone resorption, and may provide a molecular basis for therapeutic strategies against bone diseases. © 2013 American Society for Bone and Mineral Research.     

Clinical Utility and Outcome Prediction of Early ZnT8-IgG Testing and Titer in Type 1 Diabetes

Objective:Type 1 diabetes autoantibodies are directed against multiple antigens including: glutamic acid decarboxylase, protein tyrosine phosphatase-like islet antigen 2 (IA2), insulin (IAA), and Zinc transporter 8 protein (ZnT8). The aim of our study was to determine if the presence or titer of ZnT8 antibodies (Ab) was predictive for clinical presentation at diagnosis or for the subsequent disease course.Methods:Between January, 2003 and May, 2019, 105 patients aged ≤21 years with a clinical diagnosis of type 1 diabetes mellitus had at least 1 autoantibody measured. A retrospective chart review was completed. At diagnosis, we evaluated the body mass index z-score, hemoglobin (HbA1c), and the presence of diabetic ketoacidosis (DKA). Complications analyzed post-diagnosis included episodes of DKA, the diagnosis of autoimmune disease, and the presence of vascular complications. We evaluated cumulative lifetime excess glucose as HbA1c area under the curve (AUC) >6%.Results:Seventy-one patients were ZnT8-Ab(+) (68%), with 19 having low titer ZnT8-Ab and 52 with high titer ZnT8-Ab. Follow-up ranged from 10 days to 15.7 years (median 2.08 years). There were no differences in the characteristics at disease onset or in the subsequent follow-up between those with and those without ZnT8-Ab or those with high or low titers of ZnT8 Ab, except for a small but statistically significant difference in cumulative excess glucose (HbA1c AUC >6%) between those with low and high titers (p=0.0095).Conclusion:Our study adds to the limited literature on the effect of the presence and titer of ZnT8-Ab in pediatric diabetes. The small effect of ZnT8-Ab titer on glucose excess as measured by HbA1c AUC warrants further study.     

手性固定相HPLC法分离测定匹多莫德对映异构体

建立匹多莫德光学异构体检查的手性固定相HPLC法,为本品的质量控制提供有效的分析方法。色谱条件为CHIRALPAK^?IA柱(250 mm×4.6 mm,5 μm),流动相为甲基叔丁基醚-乙腈-三氟乙酸（35∶65∶0.2）,柱温25 ℃,流速为1.0 mL/min,检测波长为210 nm。在建立的色谱条件下,匹多莫德与其对映异构体可完全分离。本方法可用于匹多莫德原料中对映异构体的检测。     

Intimate partner violence as a mechanism of traumatic ocular injury in women

ObjectiveDetermine the prevalence of intimate partner violence (IPV) as a mechanism of traumatic ocular injury in women, typical injury patterns, and the clinical course of affected patients. Encourage IPV screening and safety assessment in patients presenting with characteristic ocular trauma.MethodsMedical records of 211 female patients with traumatic ocular injuries evaluated at the University of Iowa Hospitals and Clinics between January 1995 and January 2015 were reviewed to determine the rate of IPV as a mechanism of ocular trauma. Twenty-one patients were excluded due to no documented trauma.ResultsLeading causes of traumatic ocular injuries in the 190 female patients included were accidental trauma with an inanimate object (n = 70/190, 36.8%), falls (n = 52/190, 27.4%), motor vehicle collisions (n = 21/190, 11.1%), and assault (n = 16/190, 8.4%). In 2.1% of cases (n = 4/190), no mechanism of traumatic injury was documented. Assault was the fourth leading mechanism of injury accounting for 8.4% of cases (n = 16/190), with IPV accounting for more than one third of cases with a documented perpetrator (n = 5/13). No perpetrator was documented in 18.8% (n = 3/16). All 5 patients with IPV-related injuries sustained scleral laceration or rupture; 4 out of 5 patients had no light perception vision and ultimately required enucleation.ConclusionIPV is an important mechanism of traumatic ocular injury. IPV-associated injuries tend to be severe in nature, as demonstrated by the high rate of globe laceration or rupture and subsequent enucleation in the study population. By appropriate screening and referral, ophthalmologists have an opportunity to redirect a potentially devastating course.     

Two distinct phases characterize maturation of neurons in the nucleus of the tractus solitarius during early development: Morphological and electrophysiological evidence

We have used electrophysiology and light microscopy of intracellularly labeled neurons in the nucleus of the tractus solitarius (nTS) in brainstem slices of the newborn rat (PO to P6) to examine the functional and morphological correlation of their development. Three-dimensional reconstruction of neurons injected intracellularly with biocytin, following electrophysiological recording, revealed a close correspondence between morphological immaturity (appearing as polarization of the dendritic tree) and the absence of a ramp-like voltage trajectory at the offset of hyperpolarizing current injections–l_A negativity (8 of the 8 cells examined showed this correlation). These morphologically polarized I_A negative neurons showed preferential dendritic sprouting in two diametrically opposite poles of the perikaryon. The orientation of the polarity differed according to the rostrocaudal location of the neuron. The appearance of a polarized dendritic tree during the first (immature) phase was transient and closely coincident with I_A negativity. Following the development of adult-like electrophysiological characteristics, i.e., I_A positivity, nucleus of the tractus solitarius neurons showed remarkably different morphological features (9 of 10 cells). These included a widespread branching of the dendritic tree in all directions, giving it a bushy appearance (cell body to dendrite ratio of 1:40). Numerous dendritic spines, growth cones on both dendrites and axons, and axon collateralization were present during both phases and indicate that nTS neurons during the two phases of early development demonstrate dynamic features of growth and maturation. The development of adult-like electrophysiological characteristics, i.e., I_A positivity, progressively increased in the postnatal period. During the later part of the first postnatal week, twice as many neurons showed I_A positivity in days P3 to P6 as compared with days PO to P2. These results reveal the dynamic nature of neurons in the nTS during early development and illustrate the close link between morphology and functional characteristics in this region. We suggest that the establishment of adult-like morphology can be modified by appropriate environmental clues provided to nTS neurons during the initial (immature) phase of early postnatal development. © 1993 Wiley-Liss, inc.     

Somatic complaints -- harbinger of depression in primary care

The pattern of patient visits and type of complaints relating to depressive illness was investigated in a University family practice clinic. Complaints and visits of depressives were compared to those made by age and sex-matched controls over 6 time periods which spanned a period of 2 years starting 6 months prior to the diagnosis of depression. Functional, pain, anxiety, and social complaints appeared to parallel the course of the depression, rising before the diagnosis of depression and returning to control levels 15-18 months after the depression was diagnosed. Somatic complaints were a prominent part of the depressive presentation.