Ultra-high performance concrete alleviates ecotoxicological effects in aquatic organisms.

With the advancement of cementitious material technologies, ultra-high performance concretes incorporating nano- and(or) micro-sized particle materials have been developed; however, their environmental risks are still poorly understood. This study investigates the ecotoxicological effects of ultra-high performance concrete (UC) leachate by comparing with that of the conventional concrete (CC) leachate. For this purpose, a dynamic leaching test and a battery test with algae, water flea, and zebrafish were performed using standardized protocols. The conductivity, concentration of inorganic elements (Al, K, Na, and Fe), and total organic concentration were lower in the UC leachate than in the CC leachate. The EC50 values of the CC and UC leachates were 44.9 % and >100 % in algae, and 8.0 % and 63.1 % in water flea, respectively. All zebrafish exposed to the CC and UC leachates survived. A comprehensive evaluation of the ecotoxicity of the CC and UC leachate based on the toxicity classification system (TCS) showed that their toxicity classification was "highly acute toxicity" and "acute toxicity", respectively. Based on the hazard quotient and principal component analysis, Al and(or) K could be significant factors determining the ecotoxicity of concrete leachate. Furthermore, the ecotoxicity of UC could not be attributed to the use of silica-based materials or multi-wall carbon nanotubes. This study is the first of its kind on the ecotoxicity of UC leachate in aquatic environments, and the results of this study can be used to develop environment-friendly UC.

Pain Scales: What Are They and What Do They Mean.

PURPOSE OF REVIEW: It is essential to have validated and reliable pain measurement tools that cover a wide range of areas and are tailored to individual patients to ensure effective pain management. The main objective of this review is to provide comprehensive information on commonly used pain scales and questionnaires, including their usefulness, intended purpose, applicability to different patient populations, and associated advantages and disadvantages. RECENT FINDINGS: Acute pain questionnaires typically focus on measuring the severity of pain and the extent of relief achieved through interventions. Chronic pain questionnaires evaluate additional aspects such as pain-related functional limitations, psychological distress, and psychological well-being. The selection of an appropriate pain scale depends on the specific assessment objectives. Additionally, each pain scale has its strengths and limitations. Understanding the differences among these pain scales is essential for selecting the most appropriate tool tailored to individual patient needs in different settings. CONCLUSION: Medical professionals encounter challenges in accurately assessing pain. Physicians must be familiar with the different pain scales and their applicability to specific patient population.

A Case of Linear Hypertrophic Lichen Planus in a Pediatric Patient.

Lichen planus (LP) is a chronic inflammatory disease of the skin and mucosa. Of the various types, the hypertrophic type is characterized by thickened, purplish hyperkeratotic plaques and nodules. The course of hypertrophic LP tends to be more chronic than those of other types. A 12-year-old girl presented with a 2-year history of warty papules and plaques in a zosteriform configuration along one flank. Histopathology revealed hyperkeratosis and papillomatosis with wedge-shaped hypergranulosis. A lichenoid lymphocytic infiltrate with vacuolar change in the basal layer was evident. She was prescribed oral doxycycline, a topical corticosteroid, and tacrolimus. After 7 weeks, the skin lesions became significantly flattened and faded. LP is less common but more severe in children than in adults. The unilateral, linear hypertrophic type of LP is uncommon. Herein, we report a rare case of linear hypertrophic LP in a child.

Expanding Psychiatric Treatment in Primary Care Settings: Improved Care Through the Wisconsin Child Psychiatry Consultation Program.

The national shortage of child psychiatrists has resulted in the necessity of primary care providers (PCPs) managing increased mental health concerns of youth. The Wisconsin Child Psychiatry Consultation Program (WI CPCP) is one of several programs throughout the United States which provide PCPs with education, consultation, and resource support related to pediatric mental health. To evaluate initial impact of the program, data from 190 pediatricians and family practitioners from the Wisconsin Health Information Organization (WHIO) were analyzed. Enrollment in the WI CPCP was associated with a significant increase in rates of mental health diagnoses within primary care visits. In addition, the number of providers who made any mental health diagnosis increased from 56% of PCPs pre-enrollment to over 99% post-enrollment. These data provide additional support for pediatric psychiatry consultation programs within primary care.

Review: Discogenic Back Pain: Update on Treatment.

Purpose of Review: Lower back pain (LBP) has a lifetime prevalence of 80% in the United States population. Discogenic back pain (DBP), a subcategory of LBP, occurs as a result of the interverbal disc degeneration without disc herniation. Diagnosis relies on history, physical exam, and imaging such as MRI, provocative discography, or CT discography. Recent Findings: Treatment of DBP involves a multifaceted approach with an emphasis on conservative measures including behavioral modification, pharmacologic management, and other non-pharmacologic interventions with invasive therapy reserved for select patients. Due to the paucity of data on the treatment of DBP, treatment also relies on data derived from treatment of chronic LBP (CLBP). Summary: Despite the scarcity of data for the treatment of DBP, treatments do exist with varying efficacy for DBP. Novel techniques such as the use of biologics may provide another avenue for treatment though further studies are needed to better evaluate the most efficacious regimen for both novel and existing treatments.

Literature Review: Pericranial Nerve Blocks for Chronic Migraines.

Purpose of Review: Headaches, especially migraines, are one of the most pervasive neurological disorders affecting up to 15.9% of the population. Current methods of migraine treatment include lifestyle changes, pharmacologic, and minimally invasive techniques such as peripheral nerve stimulation (PNS) and pericranial nerve blocks (PNB). Recent Findings: PNBs are used to treat and prevent migraines and involves injection of local anesthetics with or without corticosteroids. PNBs include the greater occipital, supraorbital, supratrochlear, lesser occipital, auriculotemporal, sphenopalantine ganglion, and cervical root nerve blocks. Of the PNBs, the most extensively studied is the greater occipital nerve block (GONB) which has been shown to be an efficacious treatment for migraines, trigeminal neuralgia, hemi-crania continua, and post-lumbar puncture, post-concussive, cluster, and cervicogenic headaches but not medication overuse and chronic tension type headaches. Summary: In this review, we aim to summarize the recent literature on PNBs and their efficacy in the treatment of migraines including a brief discussion of peripheral nerve stimulation.

Meralgia Paresthetica Review: Update on Presentation, Pathophysiology, and Treatment.

Purpose of Review: Meralgia paresthetica (MP) is a condition characterized by paresthesias, neuropathic pain, and alterations in sensorium of the anterolateral thigh secondary to impingement of the lateral femoral cutaneous nerve (LFCN). MP is generally diagnosed by clinical history and is often a diagnosis of exclusion. When diagnosis remains a challenge, diagnostic modalities such as ultrasound, MRI, electromyography, and nerve conduction studies have been utilized as an adjunct. This review summarizes the most recent medical literature regarding MP, its pathophysiology, presentation, and current treatment options. Recent Findings: Treatment options for patients with MP range from lifestyle modifications and conservative management to surgical procedures. Initial management is often conservative with symptoms managed with medications. When conservative management fails, the next step is regional blocks followed by surgical management. The conflicting data for treatment options for MP highlight how the evidence available does not point to a single approach that's universally effective for treating all patients with MP. Summary: Despite the apparent success at treating MP with regional blocks and surgical interventions, much remains to be known about the dosing, frequency, and optimal interventions due to the inconclusive results of current studies. Further research including randomized controlled trials are needed to better understand the most optimal treatment options for MP including studies with a larger number of participants.

A Case of Vesicular Mycosis Fungoides.

A 44-year-old male presented with 7 months history of nonpruritic round oozing plaques on the extremities and red papules on the trunk. The lesions were resistant to topical and oral steroid prescribed at the other local clinics. Histopathological examination showed parakeratosis with acanthosis and rete ridge elongation as well as spongiotic intraepidermal blisters and dense dermal infiltration of small to medium sized atypical lymphoid cells. Immunohistochemical analysis revealed the lymphocyte infiltrate to be predominantly CD4+ T cells, with CD4/CD8 ratio to be greater than 10:1. Infiltration of large cells that were CD30+ were also noted. This histopathologic findings are consistent with vesicular mycosis fungoides (MF). He was prescribed with narrow-band ultraviolet B twice per week and topical steroid, combined with interferon-α injection for 5 weeks, and his skin lesions significantly faded and were flattened. Vesicular MF is associated with poor prognosis, but our patient was able to show benign course of disease thanks to timely diagnosis. One must consider vesicular MF as a differential for recalcitrant eczematous lesions.

Regional anesthesia techniques for cardiac surgery: where are we?

PURPOSE OF REVIEW: Inadequate pain relief after cardiac surgery results in decreased patient experience and satisfaction, increased opioid consumption with its associated adverse consequences, and reduced efficiency metrics. To mitigate this, regional analgesic techniques are an increasingly important part of the perioperative cardiac anesthesia care plan. The purpose of this review is to compare current regional anesthesia techniques, and the relative evidence supporting their efficacy and safety in cardiac surgery. RECENT FINDINGS: Numerous novel plane blocks have been developed in recent years, with evidence of improved pain control after cardiac surgery. SUMMARY: The current data supports the use of a variety of different regional anesthesia techniques to reduce acute pain after cardiac surgery. However, future randomized trials are needed to quantify and compare the efficacy and safety of different regional techniques for pain control after cardiac surgery.

The Impact of Smoking on the Development and Severity of Chronic Pain.

PURPOSE OF REVIEW: The purpose of this review is to examine the impact of smoking and its role on the development of chronic pain and provide a critical review of recent literature. RECENT FINDINGS: Recent studies demonstrate the bidirectional and dependent relationship between smoking and chronic pain. Those who are in pain have a more difficult time in the cessation of smoking as well as an increased sensitivity to pain during abstinence, lower confidence, and higher relapse rates. The fear of pain and the anxiety and depression that abstinence causes results in a grim outcome for long-term cessation. The dependent nature between chronic pain and smoking is affected by numerous variables. Providers should consider a multiprong approach to treating chronic pain and targeting smoking cessation treatment by providing motivational therapy, nicotine replacement, and medication therapies to prevent relapse, and providing those who are more likely to relapse with a higher level of care.

A human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery.

Chronic liver disease and hepatocellular carcinoma (HCC) are life-threatening diseases with limited treatment options. The lack of clinically relevant/tractable experimental models hampers therapeutic discovery. Here, we develop a simple and robust human liver cell-based system modeling a clinical prognostic liver signature (PLS) predicting long-term liver disease progression toward HCC. Using the PLS as a readout, followed by validation in nonalcoholic steatohepatitis/fibrosis/HCC animal models and patient-derived liver spheroids, we identify nizatidine, a histamine receptor H2 (HRH2) blocker, for treatment of advanced liver disease and HCC chemoprevention. Moreover, perturbation studies combined with single cell RNA-Seq analyses of patient liver tissues uncover hepatocytes and HRH2+, CLEC5Ahigh, MARCOlow liver macrophages as potential nizatidine targets. The PLS model combined with single cell RNA-Seq of patient tissues enables discovery of urgently needed targets and therapeutics for treatment of advanced liver disease and cancer prevention.

A case of porokeratotic adnexal ostial nevus misdiagnosed as wart.

Porokeratotic adnexal ostial nevus may be misdiagnosed as wart based on clinical appearance and morphology. An accurate diagnosis through skin biopsy is crucial, as is the inclusion of rare disorders such as porokeratotic adnexal ostial nevus in the differential diagnosis.

Epigallocatechin Gallate Induces Hepatic Stellate Cell Senescence and Attenuates Development of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly morbid condition with lack of effective treatment options. HCC arises from chronically inflamed and damaged liver tissue; therefore, chemoprevention may be a useful strategy to reduce HCC incidence. Several reports suggest that epigallocatechin gallate (EGCG), extracted from green tea, can suppress liver inflammation and fibrosis in animal models, but its role in HCC chemoprevention is not well established. In this study, male Wistar rats were injected with diethylnitrosamine at 50 mg/kg for 18 weeks to induce cirrhosis and HCC, and EGCG was given in drinking water at a concentration of 0.02%. Clinically achievable dosing of EGCG was well-tolerated in diethylnitrosamine-injured rats and was associated with improved serum liver markers including alanine transaminase, aspartate transaminase, and total bilirubin, and reduced HCC tumor formation. Transcriptomic analysis of diethylnitrosamine-injured hepatic tissue was notable for increased expression of genes associated with the Hoshida high risk HCC gene signature, which was prevented with EGCG treatment. EGCG treatment also inhibited fibrosis progression, which was associated with inactivation of hepatic stellate cells and induction of the senescence-associated secretory phenotype. In conclusion, EGCG administered at clinically safe doses exhibited both chemopreventive and antifibrotic effects in a rat diethylnitrosamine liver injury model.

Effect of nitrogen on grain growth and formability of Ti-stabilized ferritic stainless steels.

The relationship between the grain size of as-cast and cold rolled 16%Cr ferritic stainless steel and the surface roughness defect, called ridging during forming was investigated. The ridging height corresponded to the grain size of the as-cast sample. The nitrogen content of 140 ppm yielded the minimum grain size and the minimum ridging height observed, whereas the nitrogen content of 50 ppm yielded the maximum grain size and the maximum ridging height observed. Ridging results from different plastic anisotropies of band structure composed of colonies. Through the EBSD analysis, the texture of mixed colonies composed of ND//{112} and ND//{331} in the 50 ppm nitrogen steel underwent more severe ridging than the randomly texture in the 140 ppm nitrogen steel sample. Therefore, an effective means to reduce the ridging of ferritic stainless steel during the forming process is to form a random texture by enhancing the formation of fine equiaxed grain during the casting process. During equal holding times at 1200 °C, the 80 ppm nitrogen sample was definitely coarsened, whereas the 200 ppm nitrogen sample underwent slower grain growth. Zener pinning force, which is proportional to the number of TiN particles on grain boundaries, was relatively strong in samples of 200 ppm nitrogen content, corresponding to slower grain growth. Although the Zener pinning force great affected with increasing nitrogen content, there may not affect the trend of initial cast grain size to be changed as much during annealing.

Nuclear Pores Promote Lethal Prostate Cancer by Increasing POM121-Driven E2F1, MYC, and AR Nuclear Import.

Nuclear pore complexes (NPCs) regulate nuclear-cytoplasmic transport, transcription, and genome integrity in eukaryotic cells. However, their functional roles in cancer remain poorly understood. We interrogated the evolutionary transcriptomic landscape of NPC components, nucleoporins (Nups), from primary to advanced metastatic human prostate cancer (PC). Focused loss-of-function genetic screen of top-upregulated Nups in aggressive PC models identified POM121 as a key contributor to PC aggressiveness. Mechanistically, POM121 promoted PC progression by enhancing importin-dependent nuclear transport of key oncogenic (E2F1, MYC) and PC-specific (AR-GATA2) transcription factors, uncovering a pharmacologically targetable axis that, when inhibited, decreased tumor growth, restored standard therapy efficacy, and improved survival in patient-derived pre-clinical models. Our studies molecularly establish a role of NPCs in PC progression and give a rationale for NPC-regulated nuclear import targeting as a therapeutic strategy for lethal PC. These findings may have implications for understanding how NPC deregulation contributes to the pathogenesis of other tumor types.

Male germ cells support long-term propagation of Zika virus.

Evidence of male-to-female sexual transmission of Zika virus (ZIKV) and viral RNA in semen and sperm months after infection supports a potential role for testicular cells in ZIKV propagation. Here, we demonstrate that germ cells (GCs) are most susceptible to ZIKV. We found that only GCs infected by ZIKV, but not those infected by dengue virus and yellow fever virus, produce high levels of infectious virus. This observation coincides with decreased expression of interferon-stimulated gene Ifi44l in ZIKV-infected GCs, and overexpression of Ifi44l results in reduced ZIKV production. Using primary human testicular tissue, we demonstrate that human GCs are also permissive for ZIKV infection and production. Finally, we identified berberine chloride as a potent inhibitor of ZIKV infection in both murine and human testes. Together, these studies identify a potential cellular source for propagation of ZIKV in testes and a candidate drug for preventing sexual transmission of ZIKV.

Targeted Retinal Photocoagulation for Diabetic Macular Edema with Peripheral Retinal Nonperfusion: Three-Year Randomized DAVE Trial.

PURPOSE: To evaluate the effect of targeted retinal photocoagulation (TRP) on visual and anatomic outcomes and treatment burden in eyes with diabetic macular edema (DME). DESIGN: Phase I/II prospective, randomized, controlled clinical trial. PARTICIPANTS: Forty eyes of 29 patients with center-involved macular edema secondary to diabetes mellitus. METHODS: Eyes with center-involved DME and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) between 20/32 and 20/320 (Snellen equivalent) were randomized 1:1 to monotherapy with 0.3 mg ranibizumab (Lucentis, Genentech, South San Francisco, CA) or combination therapy with 0.3 mg ranibizumab and TRP guided by widefield fluorescein angiography. All eyes received 4 monthly ranibizumab injections followed by monthly examinations and pro re nata (PRN) re-treatment through 36 months. Targeted retinal photocoagulation was administered outside the macula to areas of retinal capillary nonperfusion plus a 1-disc area margin in the combination therapy arm at week 1, with re-treatment at months 6, 18, and 25, if indicated. MAIN OUTCOME MEASURES: Mean change in ETDRS BCVA from baseline and number of intravitreal injections administered. RESULTS: At baseline, mean age was 55 years, mean BCVA was 20/63 (Snellen equivalent), and mean central retinal subfield thickness (CRT) was 530 µm. Thirty-four eyes (85%) completed month 36, at which point mean BCVA improved 13.9 and 8.2 letters (P = 0.20) and mean CRT improved 302 and 152 µm (P = 0.03) in the monotherapy and combination therapy arms, respectively. The mean number of injections administered through month 36 was 24.4 (range, 10-34) and 27.1 (range, 12-36), with 73% (362/496) and 80% (433/538) of PRN injections administered (P = 0.004) in the monotherapy and combination therapy arms, respectively. Goldmann visual field isopter III-4e area decreased by 2% and 18% in the monotherapy and combination therapy arms, respectively (P = 0.30). CONCLUSIONS: In this 3-year randomized trial of 40 eyes with DME, there was no evidence that combination therapy with ranibizumab and TRP improved visual outcomes or reduced treatment burden compared with ranibizumab alone.

The XBP1 Arm of the Unfolded Protein Response Induces Fibrogenic Activity in Hepatic Stellate Cells Through Autophagy.

Autophagy and the unfolded protein response (UPR) both promote activation of hepatic stellate cells (HSC), however the link between the two stimuli remains unclear. Here we have explored the role of X-box binding protein 1 (XBP1), one of three UPR effector pathways and sought to establish the interdependence between autophagy and the UPR during HSC activation. XBP1 induction accompanied both culture-based HSC activation and ER stress induced by tunicamycin. Ectopic overexpression of XBP1 induced collagen 1-alpha expression in HSCs, which was inhibited by knockdown of ATG7, a critical autophagy mediator. Genome-wide transcriptomic profiling indicated an upregulation of collagen synthesis pathways, but not of the transforming growth factor (TGF)-b pathway, a canonical fibrogenic driver, suggesting that XBP1 activates a specific subset of fibrogenesis pathways independent of TGF-ß1. XBP1 target gene signatures were significantly induced in rodent liver fibrosis models (n = 3-5) and in human samples of non-alcoholic fatty liver disease (NAFLD) (n = 72-135). Thus, XBP1-mediated UPR contributes to fibrogenic HSC activation and is functionally linked to cellular autophagy.

Molecular Liver Cancer Prevention in Cirrhosis by Organ Transcriptome Analysis and Lysophosphatidic Acid Pathway Inhibition.

Cirrhosis is a milieu that develops hepatocellular carcinoma (HCC), the second most lethal cancer worldwide. HCC prediction and prevention in cirrhosis are key unmet medical needs. Here we have established an HCC risk gene signature applicable to all major HCC etiologies: hepatitis B/C, alcohol, and non-alcoholic steatohepatitis. A transcriptome meta-analysis of >500 human cirrhotics revealed global regulatory gene modules driving HCC risk and the lysophosphatidic acid pathway as a central chemoprevention target. Pharmacological inhibition of the pathway in vivo reduced tumors and reversed the gene signature, which was verified in organotypic ex vivo culture of patient-derived fibrotic liver tissues. These results demonstrate the utility of clinical organ transcriptome to enable a strategy, namely, reverse-engineering precision cancer prevention.