Iron Deficiency Anemia Associated With Acid-Modifying Medications: Two Cases and Literature Review

Iron deficiency anemia is often listed among potential adverse effects of gastric acid-suppressive medications, given that gastric acidity promotes intestinal absorption of nonheme iron. Additionally, the antacid calcium carbonate can inhibit iron absorption. However, there is little direct clinical evidence that proton-pump inhibitors, histamine-2 receptor antagonists, or calcium carbonate cause iron deficiency anemia. Most case reports have had substantial limitations (e.g., minimal follow-up and presence of other causes of iron deficiency), and retrospective cohort studies have lacked sufficient patient-specific detail to make strong causal inferences. We present 2 cases—both with detailed, prospective 10-year follow-up—in which combinations of proton-pump inhibitors, histamine-2 receptor antagonists and calcium carbonate were clearly associated with development of iron deficiency anemia. Overt iron-deficiency anemia is probably uncommon in patients who use acid-modifying medications and who have no other conditions that predispose to iron deficiency. Nevertheless, clinicians should be aware of this potential complication, given widespread use of these agents.     

Factors influencing development of residual stresses during crystallization firing in a novel lithium silicate glass-ceramic

ObjectiveDevelopment of residual stresses is a potential source of premature fractures in glassy materials, being of special interest in novel lithium silicate glass-ceramics that require a crystallization firing to achieve their final mechanical properties. The aim of this work was to assess the influence of various firing tray systems and the application of different cooling protocols on the development of residual stresses in Suprinity PC crowns. Their effect on the in vitro lifetime of the restorations was also studied.MethodsThirty crowns were milled out of Suprinity PC blocks and crystallized using one of five different commercial firing tray systems (n = 6). Samples in each group were cooled following a fast (FC = 5.5 °C/s), a slow (SC = 0.4 °C/s) or the manufacturer’s reference cooling (REF ). Obtained crowns were sagittally or transversally sectioned and the magnitude and distribution of residual stresses was determined using the light birefringence method. Extra crowns of three of the subgroups (n = 8) were produced and submitted to chewing simulation for 10⁶ cycles or until fracture ensued.ResultsAverage residual stresses ranged between 0 and 1.5 MPa (peaks of 5 MPa). Highest stress magnitudes were observed at the support areas of groups using firing pins, leading to thermal cracks in FC samples and premature failures in the REF subgroup. The use of fibrous pads and firing pastes limited the development of residual stresses, whereas application of SC regimes extended the lifetime of the restorations.SignificanceDevelopment of residual stresses during crystallization firing in lithium silicate glass-ceramics results critical for their mechanical performance and should be therefore avoided by ensuring a homogenous cooling of the structures.     

Glycogen synthase kinase-3: A potential preventive target for prostate cancer management

ObjectivesProstate cancers are the frequently diagnosed cancers in men, and patients with metastatic disease only have 28% chance for 5-year survival. Patients with low-risk tumors are subjected to active surveillance, whereas high-risk cases are actively treated. Unfortunately, there is no cure for patients with late-stage disease. Glycogen synthase kinase-3 (GSK-3, α and β) is a protein serine/threonine kinase and has diverse cellular functions and numerous substrates. We sought to summarize all the studies done with GSK-3 in prostate cancers and to provide a prospective direction for future work.Methods and materialsA comprehensive search of the literature on the electronic databases PubMed was conducted for the subject terms of GSK-3 and prostate cancer. Gene mutation and expression information was extracted from Oncomine and COSMIC databases. Case reports were not included.ResultsAccumulating evidence indicates that GSK-3α is mainly expressed in low-risk prostate cancers and is related to hormone-dependent androgen receptor (AR)–mediated gene expression, whereas GSK-3β is mainly expressed in high-risk prostate cancers and is related to hormone-independent AR-mediated gene expression. GSK-3 has been demonstrated as a positive regulator in AR transactivation and prostate cancer growth independent of the Wnt/β-catenin pathway. Different types of GSK-3inhibitors including lithium show promising results in suppressing tumor growth in different animal models of prostate cancer. Importantly, clinical use of lithium is associated with reduced cancer incidence in psychiatric patients.ConclusionsTaken together, GSK-3 inhibition might be implicated in prostate cancer management as a preventive treatment.     

Polyhydroxymethylenes as Multifunctional High Molecular Weight Sugar Alcohols Tailored for 3D Printing and Medical Applications

Common sugar alcohols used as artificial sweeteners and components of polymer networks represent low molecular weight polyhydroxymethylenes (PHMs) with the general formula [CH(OH)]_nH₂ but very low degree of polymerization (n = 2–6). Herein high molecular weight PHM (n >> 100) unparalleled in nature is tailored for 3D printing and medical applications by free radical polymerization of 1,3‐dioxol‐2‐one vinylene carbonate to produce polyvinylene carbonate (PVCA) which yields PHM by hydrolysis. Furthermore, PVCA is solution processable and enables PHM functionalization, membrane formation, and extrusion‐based 3D printing. Opposite to cellulose, amorphous PHM is plasticized by water and is readily functionalized via PVCA aminolysis/hydrolysis to produce polyhydroxymethylene urethane (PHMU), enable PHM crosslinking and coupling of PHM with amine‐functional components like gelatin. After hydrolysis/aminolysis the original PVCA shapes are retained. PVCA solution casting yields PVCA and PHM which exhibits uniform and hierarchic pore architectures. Asymmetric membranes, hydrogels, PHM/collagen blends, and electrospun nonwovens of PVCA, PHM, and PHMU are readily tailored for medical applications. 3D printing of PVCA dispersions containing hydroxyapatite affords porous PVCA, PHMU, and PHM scaffolds useful in regenerative medicine. PHM and functionalized PHMs as carbohydrate‐inspired multifunctional materials indicate in vitro biocompatibility and hold great promise for applications in medicine and health care.     

Combination of lithium and electroconvulsive therapy (ECT) is associated with higher odds of delirium and cognitive problems in a large national sample across the United States

BackgroundLithium is a helpful adjunct to patients undergoing ECT. However, only case reports and limited data suggest increase risk of delirium. Thus, this continues to be a controversial issue.ObjectiveIn this study, we examine 1) The association and odds of delirium and cognitive problems with ECT and lithium (ECT + Li) combination compared to ECT alone, 2) If positively associated, would this association vary by both type of mood episode and type of disorder?MethodsA national sample of 64,728 adult psychiatric inpatients across the US (identified from a total data of about 70 million total discharges annually) was analyzed using linear-by-linear association and logistic regression to assess the odds ratio (OR) for delirium and cognitive impairment for those treated with lithium (N = 158), ECT (N = 64148), or ECT + Li (N = 422) after adjusting for demographics and psychiatric diagnoses.ResultsThe prevalence of delirium was higher in the ECT + Lithium group (5.7%) vs. ECT only (0.6%) or lithium only groups (0%). Patients managed with ECT + Lithium have 11.7-fold higher odds (95% CI 7.55–17.99, P < 0.001) of delirium compared to ECT alone. In the ECT + Li group, delirium prevalence was 7.8% in unipolar depression, 3.4% in bipolar depressed, 0% in bipolar mania.ConclusionThese results are surprising given the fading concern about delirium association with ECT + lithium combination. The high odds in the combination group warrant clinical caution, use of lower lithium doses (if combinations cannot be avoided), and vigilance regarding early signs of delirium. These results warrant replication in future studies.     

利培酮联合碳酸锂治疗分裂情感性精神病的疗效分析

目的分析利培酮联合碳酸锂治疗分裂情感性精神病的疗效。方法选取2013年4月~2015年1月我院收治的60例分裂情感性精神病患者,将其按照数字表法分为对照组(n=25)和治疗组(n=35),比较两组患者的治疗效果。结果治疗前后前后的抑郁、燥狂评分比较,P0.05,差异具有统计学意义;对照组患者不良反应的发生率20%高于治疗组的3%,P0.05,差异具有统计学意义。结论利培酮联合碳酸锂治疗分裂情感性精神病能有效的改善患者的抑郁和燥狂情绪。     

诱发和加重银屑病的药物研究进展

药物摄入可能是诱发或加重银屑病的重要原因,某些药物可能会直接导致易感个体发生银屑病,也可能引起原有银屑病病情复发或加重.药物和银屑病的相关性可分为:明确可诱发和加重银屑病的药物(如锂制剂等);可能与银屑病发生和加重的相关药物(如干扰素等).关于药物诱发和加重银屑病的临床和组织学数据分析有助于银屑病发病机制的研究,这些可能与银屑病诱发或加重的相关药物尚需进一步的研究,对易感个体的预防有重要的意义.     

Droplet fragmentation: 3D imaging of a previously unidentified pore-scale process during multiphase flow in porous media

Using X-ray computed microtomography, we have visualized and quantified the in situ structure of a trapped nonwetting phase (oil) in a highly heterogeneous carbonate rock after injecting a wetting phase (brine) at low and high capillary numbers. We imaged the process of capillary desaturation in 3D and demonstrated its impacts on the trapped nonwetting phase cluster size distribution. We have identified a previously unidentified pore-scale event during capillary desaturation. This pore-scale event, described as droplet fragmentation of the nonwetting phase, occurs in larger pores. It increases volumetric production of the nonwetting phase after capillary trapping and enlarges the fluid−fluid interface, which can enhance mass transfer between the phases. Droplet fragmentation therefore has implications for a range of multiphase flow processes in natural and engineered porous media with complex heterogeneous pore spaces.Multiphase fluid displacement processes in porous media are important for a broad range of natural and engineering applications such as transport of nonaqueous phase liquid contaminants in aquifers, oil and gas production from hydrocarbon reservoirs, subsurface CO₂ storage, or gas transport in fuel cells. Herein, capillary trapping is a fundamental mechanism that causes immobilization of a portion of the resident nonwetting phase when it is displaced by an invading wetting phase. As a result, production of the nonwetting phase is always less than 100%.The pore-scale physics of capillary trapping are broadly understood, as the underlying mechanisms such as piston-like displacement, snap-off and film development have been observed in physical micromodel experiments and quantitative theories have been established for them (1–4). The conventional view considers such pore-scale processes to occur between multiple pores, i.e., they are interpore processes and the pores are defined as volumes connected by narrower pore throats. By contrast, intrapore processes, as presented in this paper, are not well established in the literature. During drainage (i.e., where a nonwetting phase displaces the wetting phase), the wetting phase can establish films in the corners of the pores, which results in its continuous production and hence low residual saturations of the wetting phase. During imbibition (i.e., where the wetting phase displaces a nonwetting phase), swelling of the corner wetting films causes snap-off of the nonwetting phase, which results in capillary trapping of the nonwetting phase. The trapped nonwetting phase exists as disconnected ganglia within the pore network. Numerical pore network models have been developed to include these pore-level mechanisms with the aim of predicting the macroscopic flow properties of porous materials such as the structure of the phase distributions, residual saturation, relative permeability functions, and capillary pressure curves. Some of these models, referred to as quasi-static models, assume that fluid flow is only governed by capillary forces (5–8), and hence are limited in capturing the dynamics of fluid displacements that occur under the action of both capillary and viscous forces. In another class of pore network models, referred to as dynamic models (9–11), capillary and viscous forces are considered simultaneously. Such models are more applicable in modeling the dynamics of pore-scale events controlled by both capillary and viscous forces.The saturation distribution of two immiscible fluid phases in a porous medium is influenced by the wettability of the system, i.e., the distribution of surfaces that are preferentially water wet or preferentially wetting to a nonaqueous phase such as oil (12). It is known that a trapped nonwetting phase can be remobilized and recovered when the wetting phase is injected at capillary numbers N_c that exceed a critical level. N_c is a dimensionless ratio quantifying the relative importance of viscous to capillary forces, i.e., N_c = vµ/σ where v is the apparent velocity, µ is the viscosity of the invading phase, and σ is the interfacial tension (13). For homogeneous sandstones, remobilization typically occurs at N_c of the order of 10⁻⁵, an effect known as capillary desaturation (14).Recent advances in X-ray computed microtomography (µCT) methods have enabled the visualization and quantitative analysis of the static distribution of fluid phases, fluid rock interactions, and the structure of wetting and nonwetting phases in porous materials (8, 15). A particular focus has been on capillary trapping (16–20). Using synchrotron X-ray μCT facilities, it has also become possible to visualize dynamic pore-scale mechanisms, including snap-off and Haines jumps (21). Most of these imaging studies have focused on relatively homogeneous pore systems such as bead packs (22), sand packs (22–26), and sandstones (8, 18, 21, 23), but less attention has been paid to carbonate rocks. However, more than 50% of the world’s remaining oil reserves are located in carbonate reservoirs (27), and carbonate aquifers supply water wholly or partially to one quarter of the global population (28). Carbonates rocks can have complex multiscale pore structures, which render the application of X-ray µCT more challenging because of the need to select a representative sample that is small enough to achieve high resolutions on µCT images but that also captures the essential heterogeneities of the pore structure (29, 30).In this contribution, we use X-ray µCT to quantify the structure and distribution of a nonwetting phase (oil) after drainage and after its displacement by a wetting phase (brine) at low and high capillary numbers in a heterogeneous carbonate with multiple pore scales. Using image analysis, we demonstrate the effect of capillary desaturation on the cluster size distribution of the trapped oil phase. We identify a previously unidentified pore-scale event, which we refer to as droplet fragmentation. Droplet fragmentation is responsible for further production of the oil phase beyond capillary trapping. This fragmentation process occurs mainly in larger pores. It results in the production of additional oil from these large pores, contributes to a change in the structure of residual oil, and increases the oil−brine surface area. As a consequence, the trapped phase may subsequently be more difficult to mobilize after droplet fragmentation has occurred but mass transfer between the phases can increase.