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• Infants born with ambiguous genitalia or nonpalpable testes need to be evaluated for congenital adrenal hyperplasia as it can be life threatening. • Adrenal steroid levels vary with gestational age. • Adrenal insufficiency should be treated with hydrocortisone to avoid adrenal crisis. High doses of hydrocortisone contain mineralocorticoid activity.

Background: Gender-affirming hormone therapy is critical to the management of transgender persons. Cyproterone acetate (CPA) is a synthetic, progesterone-like compound commonly used in high doses a...

This article investigates the fin- and finger-number dependence of the total ionizing dose (TID) degradation in 16-nm bulk Si FinFETs at ultrahigh doses. n- and p-FinFETs designed with different numbers of fins and fingers are irradiated up to 500 Mrad(SiO2) and then annealed for 24 h at 100 degrees C. The TID responses of nFinFETs are insensitive to the fin number, as dominated by border and interface trap generation in shallow trench isolation (STI) and/or gate oxide. However, pFinFETs show a visible fin-number dependence with worst tolerance of transistors with the smallest number of fins. The fin number dependence may be related to a larger charge trapping in STI located at the opposite lateral sides of the first and last fins. In addition, both n- and p-FinFETs exhibit an almost TID insensitivity to the finger number. During the design of integrated circuits, the TID tolerance of electronic systems can be enhanced by preferably using transistors with a higher number of fins than fingers.

SARS-CoV-2 virus was found to be targeted cells may be located in the lower respiratory tract, COVID-19 infection can cause mild, moderate to severe symptoms. The main symptoms that appear are fever (> 38oC), cough and difficulty breathing. Vitamin C treatment has an antiviral effect. Clinical trials have shown that administering high doses of vitamin C has a beneficial effect against colds. As a nurse, one of the roles as an extension agent can be carried out in handling Covid-19 patients, namely providing communication, information, and education about health to the community. The role of nurses in providing education to the community is very necessary because it can make people who are given education understand the information conveyed. In this Community Service activity, the focus is on teenagers as one of the preventive efforts against the transmission of the Covid-19 virus through the provision of Health Education on the importance of consuming vitamin C according to the needs of the adolescent body.

Up to 93% of the human immunodeficiency virus (HIV) latent reservoir comprised defective proviruses, suggesting that a functional cure is possible through the elimination of a small population of cells containing intact virus, instead of the entire reservoir. Cyclophosphamide (Cy) is an established chemotherapeutic agent for immune cell cancers. In high doses, Cy is a nonselective cytoreductor, used in allogeneic stem-cell transplantation, while in a low dose, metronomic schedule, Cy selectively depletes regulatory T cells (Tregs). We administered low and high doses to simian immunodeficiency virus (SIV)-infected rhesus macaques (RM) to assess their effects on the SIV reservoirs. As a Treg-depleting agent, Cy unselectively depleted Treg and total lymphocytes, resulting in minimal immune activation and no viral reactivation. As a cytoreductive agent, Cy induced massive viral reactivation in elite controller RMs without ART. However, when administered with antiretroviral therapy (ART), Cy had substantial adverse effects, including mortality. Our study thus dissuades further investigation of Cy as an HIV cure agent.

Diamorphine is a strong opioid licensed in the UK for many uses, including moderate and severe pain. In the early 2000s, its use in palliative medicine was widespread before a supply disruption led to preferential use of alternative, cheaper opioids. Though these supply issues were resolved, the use of diamorphine in palliative medicine has remained reduced, particularly with another UK supply disruption in 2021. Following anecdotal reports of good results from diamorphine use in younger patients, this piece discusses two cases of young patients with metastatic cancers suffering significant pain and psychological distress. Both patients were approaching end of life and required high doses of opioids, benzodiazepines and co-analgesics, all given to limited benefit. Both patients were rotated to diamorphine giving objective and subjective improvement in symptoms. These cases are presented in the context of newer information and description of the biochemical actions of diamorphine and its metabolites, which exert their own clinical effect before themselves generating active metabolites. Various trials on, and discussion about, diamorphine’s unique metabolism and subsequent central nervous system effects help argue for its use in situations where extreme pain and psychological distress overlap.

To assess the impact of the route of administration and doses of second-generation antipsychotics (SGAs) on treatment adherence, hospital admissions, and suicidal behaviour in patients with severe schizophrenia (Clinical Global Impression–Severity–CGI-S ≥ 5), we implemented an observational 5-year follow-up study. A total of 37.5% of the patients on oral antipsychotics (Aps) and 11.5% of those on long-acting injectables (LAIs) abandoned the treatment (p < 0.001). There were no differences in treatment discontinuation between the LAI-AP standard and high-dose groups. A total of 28.1% of the patients on oral Aps had at least one hospitalisation, as well as 13.1% of patients on LAIs (p < 0.001). There were fewer hospitalisations of patients on LAIs in the high-dose group (p < 0.05). Suicide attempts were recorded for 18% of patients on oral Aps but only for 4.6% of patients on LAIs (p < 0.001). No differences were found between the dosage groups on LAIs. Tolerability was good for all Aps and somewhat better for LAIs than oral Aps in terms of side effects (p < 0.05). There were no differences between the standard and high-dose groups. More patients discontinued treatment due to side effects in the oral AP group (p < 0.01). LAI SGA treatment was more effective than oral AP in terms of adherence and treatment outcomes for managing people with severe schizophrenia. Moreover, significant improvements were found that favour high-dose LAI SGA treatment for some of these patients. This study highlights the need to consider LAI antipsychotics and high-dose strategies for patients with severe schizophrenia.

Los tumores hepáticos constituyen un importante problema de salud a nivel mundial que en multitud de ocasiones va asociado a patologías previas y factores de riesgo como las hepatitis víricas B y C, el consumo excesivo de alcohol y el aumento de casos de esteatohepatitis no alcohólica, cada vez más relevante en los países industrializados.En hepatocarcinomas no susceptibles de resección quirúrgica, la braquiterapia se está mostrando muy eficaz frente a la quimioterapia sistémica y transarterial, por lo que se desarrollan nuevos tratamientos locorregionales mínimamente invasivos y con menor toxicidad.La radioembolización hepática es una forma de braquiterapia consistente en la administración por vía arterial de microesferas marcadas con radionucleidos emisores beta negativos que en el tejido hepático tienen una escasa penetración, lo que permite la administración de dosis elevadas que provoquen daño celular en el tejido tumoral, de manera que se evita la irradiación de tejido sano contiguo.Entre las microesferas más utilizadas se encuentran las de resina y/o vidrio marcadas con 90Y, aunque actualmente se está incrementando el uso de las de 166Ho sobre matriz biodegradable de ácido poli-L-láctico, los motivos principales residen en las características de este radionucleido, como son la emisión beta de menor energía, el periodo de semidesintegración más corto y presentar, además, emisión de fotones gamma, lo que permite su seguimiento gammagráfico. Asimismo, es un elemento paramagnético, por lo que se puede detectar mediante resonancia magnética, lo que facilita la simulación previa al tratamiento y el seguimiento posterior de este.

BACKGROUND: Being a rare condition, the incidence of chylothorax among neonates is low, but the mortality rate is high. In a dire effort to reduce the risk of death, octreotide treatment is used to effectively treat acquired and congenital chylothorax. Octreotide is proven to effectively treat chylothorax in pre-term and full-term neonates. However, previous studies have not consistently demonstrated the optimal dose of octreotide or the best mode of administration. The objectives of this work were to review previous literature to determine the outcomes of administering high doses of octreotide compared to lower dose regimens in neonates with chylothorax and to determine best practices. METHODS: A literature search was performed using electronic databases using the key words neonates, chylothorax, and octreotide. RESULTS: Octreotide has been administrated in doses ranging from 0.5μg/kg/h to > 20μg/kg/h. Both low- and high-doses of octreotide are effective in resolving chylothorax with little to no side effects. When side effects were reported, neonates experienced side effects that are less significant in nature and scope. CONCLUSIONS: We recommend that the dose of octreotide in neonatal chylothorax can be titrated safely to a maximum of 20μg/kg/h without significant side effects.

Introducción: Los objetivos de este trabajo son revisar y resumir los datos publicados hasta el momento que relacionen el uso de estatinas con el riesgo de aparición o de agravamiento de glaucoma y plantear una hipótesis que explique los efectos protectores de las estatinas y su asociación con un menor riesgo de glaucoma. Método: se realizó una revisión en PubMed usando los términos “statins, hmg coa” o “hmg coa inhibitors” y “glaucoma” o “open angle glaucoma” o “intraocular pressure”. Se seleccionaron todos los artículos que incluían estudios clínicos o meta-análisis y se excluyeron comentarios, cartas a editor, artículos retractados e investigación en modelos animales. Todos los artículos fueron posteriores a 2004. Se emplearon en la revisión 17 artículos. Resultados: la mayor parte de los estudios muestran un efecto protector de las estatinas frente a la aparición y agravamiento del glaucoma de ángulo abierto. Sin embargo, otros estudios no llegan a encontrar una relación significativa e incluso alguno muestra una relación entre el glaucoma y el empleo de estatinas a altas dosis. Los efectos neuroprotectores y la inhibición de la Rho-quinasa podrían explicar los efectos encontrados. Conclusiones: la evidencia publicada no es suficiente como para recomendar el tratamiento con estatinas con el objetivo de prevenir el avance o la aparición del glaucoma., Introduction: The objectives of this article are to review and summarize the updated published data that show the relation between treatment with statins and the incidence and progression of glaucoma. We also aimed to pose a hypothesis to explain the protective effects of statins and its association with glaucoma risk. Method: a review of the literature was carried out in the PubMed database considering the MeSH terms “statins, hmg coa” or “hmg coa inhibitors” and “glaucoma” or “open angle glaucoma” or “intraocular pressure”. All articles including clinical studies and meta-analysis were selected. Comments, letters to editors, retracted articles and research on animal models were excluded. All the articles were published from 2004. 17 articles were finally selected for review. Results: most of the studies showed a protective effect of statins on incidence or progression of open angle glaucoma. Nevertheless, other studies did not find a significant association and even one study found association between statin treatment at high doses and more incidence of glaucoma. Neuroprotective effects of statin and inhibition of Rho-kinase may help explain the described effects. Conclusions: The published results are not enough evidence to support statin recommendation as preventive treatment for the incidence or progression of glaucoma.

PURPOSE To derive the isodose line R relative to the prescription dose below which irradiated normal tissue (NT) regions benefit from a hypofractionated schedule with an isoeffective dose to the tumor. To apply the formalism to clinical case examples. METHODS From the standard biologically effective dose (BED) equation based on the linear-quadratic (LQ) model, the BED of an NT that receives a relative proportion r of the prescribed dose per fraction for a given α/β-ratio of the tumor, (α/β)T , and NT, (α/β)NT , is derived for different treatment schedules while keeping the BED to the tumor constant. Based on this, the "break-even" isodose line R is then derived. The BED of NT regions that receive doses below R decreases for more hypofractionated treatment schedules, and hence a lower risk for NT injury is predicted in these regions. To assess the impact of a linear behavior of BED for high doses per fraction (>6 Gy), we evaluated BED also using the LQ-linear (LQ-L) model. RESULTS The formalism provides the equations to derive the BED of an NT as function of dose per fraction for an isoeffective dose to the tumor and the corresponding break-even isodose line R. For generic α/β-ratios of (α/β)T = 10 Gy and (α/β)NT = 3 Gy and homogeneous dose in the target, R is 30%. R is doubling for stereotactic treatments for which tumor control correlates with the maximum dose of 100% instead of the encompassing isodose line of 50%. When using the LQ-L model, the notion of a break-even dose level R remains valid up to about 20 Gy per fraction for generic α/β-ratios and DT=2(α/β) . CONCLUSIONS The formalism may be used to estimate below which relative isodose line R there will be a differential sparing of NT when increasing hypofractionation. More generally, it allows to assess changes of the therapeutic index for sets of isoeffective treatment schedules at different relative dose levels compared to a reference schedule in a compact manner.

Polymyalgia rheumatica (PMR) is common. The mainstay of treatment, glucocorticoids, are associated with significant adverse effects and many patients remain on high doses for a number of years. Little is known about the use of other, non-pharmacological therapies as adjuncts in PMR. The PMR Cohort Study is an inception cohort study of patients diagnosed with PMR in primary care. This analysis presents data on the use and perceived impact of non-pharmacological therapies from a long-term follow-up survey. Non-pharmacological treatments were classified as either diet, exercise, or complementary therapies. Results are presented as adjusted means, medians, and raw counts where appropriate. One hundred and ninety-seven participants completed the long-term follow-up questionnaire, of these 81 (41.1%) reported using non-pharmacological therapy. Fifty-seven people reported using a form of complementary therapy, 35 used exercise and 20 reported changing their diet. No individual non-pharmacological therapy appeared to be associated with long-term outcomes. The use of non-pharmacological therapies is common amongst PMR patients, despite the paucity of evidence supporting their use. This suggests that people perceive a need for treatment options in addition to standard glucocorticoid regimens. Further research is needed to understand patients’ aims when seeking additional treatments and to strengthen the evidence base for their use so that patients can be guided towards effective options.

Objective Ketamine is an anesthetic that induces neurotoxicity when administered at high doses. In this work, we explored the protective effects of lipoxin A4 methyl ester (LXA4 ME) against ketamine-induced neurotoxicity and the underlying protective mechanism in pheochromocytoma (PC12) cells. Methods PC12 cells were treated with 50 μM of ketamine and different LXA4 ME concentrations of LXA4 ME (5–50 nM) for 24 h, and their viability, apoptosis, and oxidative status were assessed. Results Quantitative real-time polymerase chain reaction experiments showed that ketamine downregulated miR-22 expression and upregulated Bcl-2-associated athanogene 5 (BAG5) in PC12 cells in a concentration-dependent manner. LXA4 ME induced the opposite effects, thus attenuating ketamine-induced neurotoxicity. Further in vitro assays showed that miR-22 directly targeted BAG5, thus promoting cell viability by suppressing cell apoptosis and oxidative stress. Under expression miR-22 or upregulation of BAG5 antagonized the effects of LXA4 ME. Conclusion LXA4 ME can protect PC12 cells from ketamine-induced neurotoxicity by activating the miR-22/BAG5 signaling pathway. Thus, LXA4 ME can be used as a protective drug against ketamine-induced neural damage.

Batrachochytrium dendrobatidis (Bd) is a pathogenic fungus known to infect amphibians and crayfish. In crayfish, Bd causes gill tissue damage, and in some cases, mortality. Most research has focused on the amphibian-Bd system, so to date, little is known about the effects of Bd on the crayfish host. Here, we studied the effects of sublethal exposure to Bd and the metabolites produced by Bd on crayfish Procambarus alleni survival, gill damage, and oxygen consumption (as a proxy for mass-specific metabolic rate). Oxygen consumption increased 24 h post-exposure to live Bd, indicative of a stress response, followed by a decrease in oxygen consumption over time (χ21 = 6.39, p = 0.012). There was no difference in response when comparing the crayfish exposure to live Bd and Bd-metabolites alone (χ21 = 2.70, p = 0.101), indicating that the metabolites may have been the causative agent responsible for the response. Additionally, oxygen consumption decreased with gill damage (tissue recession) in Bd-exposed individuals. We found that high doses of Bd cause outright mortality in crayfish, and we show here that sublethal Bd-induced inhibition of oxygen consumption could negatively impact crayfish in the field, possibly reducing their overall fitness. More research is needed to understand this understudied host-parasite system. It is essential that we incorporate the disease dynamics associated with Bd and crayfish in conservation disease models, as this is the only way to develop comprehensive community-based models.

WOS:000704610500004 ESCI PubMed ID34651109 Objective: The purpose of this study was to look into the relationship between breast size and mammographic breast density in women and breast radiation dose on full-field digital mammography (FFDM), as well as the factors that influence radiation dose. Materials and Methods: The study included a total of 2,060 FFDM images from 515 consecutive participants. The participants were divided into two groups: those exposed to high doses (>3 mGy) and those exposed to low doses (

To cope with the shortage of filtering facepiece respirators (FFRs) during the coronavirus (COVID-19) pandemic, healthcare institutions were forced to reuse FFRs after applying different decontamination methods including gamma-irradiation (GIR). The aim of this study was to evaluate the effect of GIR on the filtration efficiency (FE) of FFRs and on SARS-CoV-2 detection. The FE of 2 FFRs types (KN95 and N95-3 M masks) was assessed at different particle sizes (0.3–5 µm) following GIR (0–15 kGy) delivered at either typical (1.65 kGy/h) or low (0.5088 kGy/h) dose rates. The detection of two SARS-CoV-2 RNA genes (E and RdRp4) following GIR (0–50 kGy) was carried out using RT-qPCR assay. Both masks showed an overall significant (P P ≤ 0.001) in the cycle threshold values (ΔCt) of both genes, with no detection following high doses. In conclusion, complete degradation of SARS-CoV-2 RNA can be achieved by high GIR (≥ 30 kGy), suggesting its potential use in FFRs decontamination. However, GIR exhibited adverse effects on FE in dose- and particle size-dependent manners, rendering its use to decontaminate FFRs debatable.

Местные анестетики (МА), как и все другие медикаменты, могут вызвать нежелательные явления. В отличие от крайне редких (приблизительно 1 : 1 000 000) аллергических реакций на МА интоксикация местными анестетиками (ИМА) значительно более вероятна (инцидентность приблизительно 1 : 1000), особенно с относительно высокими дозами, применяемыми для эпидуральных или больших блокад нервов. Лечение тяжелой ИМА от современных анестетиков мощного и длительного действия (например, бупивакаины) было очень трудным и почти безнадежным до успешного «липидного спасения» довольно высокими внутривенными дозами липидной эмульсии у крыс в 1998 году, затем у пациентов в 2006 году. Этот революционный метод (20% липидная эмульсия болюсом 100 мл в течение 2–3 минут, затем инфузией 200–250 мл в течение 15–20 хвилин, если не восстановится стабильность гемодинамики — рассмотреть повторный болюс или ускорение инфузии), образно названный «серебряной пулей» против ИМА, сначала рекомендовался лишь как средство отчаяния в случае безуспешной реанимации. Однако рекомендации Американского общества региональной анестезии 2010, 2012 и 2017 годов последовательно становились все менее консервативными, и теперь «липидное спасение» рекомендуется при первых признаках серьезной ИМА, сразу после обеспечения проходимости дыхательных путей. Вывод: один литр 20% липидной эмульсии должен находиться на каждом рабочем месте, где выполняют эпидуральную анестезию или большие блокады нервов высокими дозами МА.

Background Conventional buprenorphine inductions for OUD are clinically useful but require patients to experience mild to moderate opioid withdrawal symptoms to avoid precipitated withdrawal. This may be intolerable/unreasonable for some, which may have precluded successful buprenorphine treatment in the past. Microdosing buprenorphine, allowing for full agonist opioid overlap, has emerged as a clinically useful strategy for those unable to complete conventional buprenorphine induction. However, many questions remain such as preclusions regarding the amount of full agonist opioid overlap, speed of buprenorphine microdose titration, and overcoming implementation barriers in U.S. hospitals. Case presentation A female between the ages of 30 and 40 with severe OUD admitted to the hospital for IDU-related osteomyelitis wished to begin buprenorphine for OUD. Her hospitalization was subject to premature discharge at any time due to competing interests of potential foreclosure on her home, so buprenorphine needed to be started rapidly for safety and improved outcomes. Due to her significant acute pain requirements managed with full agonist opioids, it was unreasonable to consider conventional buprenorphine induction. Buprenorphine microdose strategy was employed at more rapid titration and previously described in the literature, starting at 1 mg TDD on day 1, 3 mg TDD on day 2, and 8 mg TDD on day 3 with full agonist opioid overlap starting at 1,944 MME tapered down to 473 MME. The patient prematurely left the hospital, at which time buprenorphine 8 mg TDD was held at this dose for days 3–8 while full agonist opioid was tapered from 473 MME to 117 MME. BUP was then further titrated to 8 mg TID. This patient tolerated buprenorphine microdosing well, without any treatment-emergent opioid symptoms or worsening of baseline symptoms. Discussion This case demonstrates the success of buprenorphine microdose induction despite very high doses of full agonist opioid overlap and demonstrates the ability to titrate buprenorphine microdoses faster than originally described. Strategies to overcoming implementation barriers are also discussed.

In 2019, some restrictions for use of valproic acid in women with reproductive potential by regulatory authorities and the original drug manufacturer based on the results of studies in real clinical practice were introduced. During 2019–2021, there were a further clinical data accumulation and labeling changes. The review presents a critical analysis of the changes in prescribing information and product label. There is a long lead time from the moment when safety data become known to the moment when changes are made to the medicinal product label and patient brochures. Some of the changes, including the need for high doses of folic acid to prevent neural tube defects, are debatable. Repealing the provision for mandatory archiving of informed consent forms for valproic acid use in girls and women raises legal risks. Improvements in pregnancy prevention programs and further research on the safety of valproic acid in real-world clinical settings are needed.

Igor Aleksander Bednarski,1 Magdalena Ci&aogon;&zdot;y&nacute;ska,2 Jacek Kabzi&nacute;ski,3 Ireneusz Majsterek,3 Dorota Sobolewska-Sztychny,1 Joanna Narbutt,1 Aleksandra Lesiak1 1Department of Dermatology, Pediatric Dermatology and Dermatological Oncology, Medical University of Lodz, Lodz, 91-347, Poland; 2Nicolaus Copernicus Multidisciplinary Centre for Oncology and Traumatology, Lodz, 93-513, Poland; 3Department of Chemistry and Clinical Biochemistry, Medical University of Lodz, Lodz, 90-136, PolandCorrespondence: Igor Aleksander BednarskiDepartment of Dermatology, Pediatric Dermatology and Dermatological Oncology, Medical University of Lodz, Kniaziewicza 1/5, Lodz, 91-347, PolandEmail igorbednarskiv@gmail.comIntroduction: Photoaging is a premature skin aging developing secondarily to the excessive exposure to ultraviolet radiation. Due to its complexity, an exact mechanism of photoaging has not been found yet; however, recent research has shown two new emerging players in this process – cathepsin K and progerin.Aim: To evaluate how different wavelengths of ultraviolet radiation (UVA, narrowband UVB and broadband UVB) influence cathepsin K and progerin protein and mRNA expression in dermal cultured fibroblasts.Materials and Methods: Primary human dermal fibroblasts (Detroit 551, ATCC CCL-110) were cultured and irradiated with UVA, narrowband UVB (UVBnb) and broadband UVB (UVBwb). Fibroblasts were irradiated with 2 protocols: single high-dose exposure to UVR with protein/mRNA extraction immediately after exposure, 24 h after exposure and 48 h after exposure, and repeated (0 h, 24 h and 48 h) low-dose exposure to UVR with protein/mRNA extraction 48 h after first exposure.Results: Single high doses of UVA, UVBwb and UVBnb resulted in decreased expression of cathepsin K and progerin protein/mRNA in all subsequent time points. Repeated exposure to low doses of UVA results in significant increase of progerin mRNA and significant decrease of progerin protein after 48 h, but repeated exposure to UVBwb and UVBnb resulted in decreased progerin mRNA and protein expression. Repeated exposure to UVA, UVBwb and UVBnb resulted in decreased cathepsin K protein and mRNA expression.Conclusion: The results suggest that there could be another progerin/cathepsin K regulatory pathway, which has not been described yet. Being contradictory with previous research, the influence of ultraviolet radiation on progerin and cathepsin K needs to be further elucidated.Keywords: progerin, cathepsin K, photoaging

The interest and search for natural active principles with therapeutic properties from plants are growing, given their potential for use by the cosmetic and pharmaceutical industries. Thus, the objective of this review was to carry out a systematic analysis of scientific productions that have explored some therapeutic potential of Caryocar brasiliense. The methodology of the preferred reporting items was adopted for systematic review and meta-analysis protocols (PRISMA). Articles published in the period from 2009 to 2019 in the Web of Science and Bireme were selected and evaluated. The descriptors used were C. brasiliense, extract, and therapeutic. After applying the exclusion criteria, 25 studies were selected, elucidating a miscellany of therapeutic potentials for pequi, such as antioxidant, antifungal, antibiotic, antineoplastic, neuroprotective, regulation of blood pressure as well as analysis of the toxicity of different parts of the plant. It was verified that the pulp extract was the most used for therapeutic purposes, mainly orally. Toxicological studies have shown low toxicity for all parts of the plant, in high doses. The therapeutic benefits observed consisted mainly of antioxidant, anti-inflammatory, antimicrobial, antineoplastic, antiparasitic, and blood pressure control activities. Key words: Caryocar brasiliense, extracts, systematic review, therapeutic potential.

На сьогодні у зв’язку зі значною поширеністю дефіциту вітаміну D все більше застосовуються болюсні схеми призначення високих доз вітаміну D у різних режимах. У статті наведено обґрунтування застосування високих доз вітаміну D, висвітлено питання гіпервітамінозу D й гіперчутливості до вітаміну D, подані аналіз літературних даних ефективності застосування препаратів вітаміну D у дозі 50 000 МО при деяких соматичних захворюваннях, а також результати власних експериментальних досліджень впливу високих доз вітаміну D на показники кісткової тканини в щурів старечого віку із системним остеопорозом та його ускладненнями.

Hidroquinon digunakan secara klinis sebagai bahan topikal untuk kondisi depigmentasi seperti chloasma dan melasma, namun pemakaian hidrokuinon melebihi 2% dapat menyebabkan iritasi. Kadar hidrokuinon melebihi 5% dapat menimbulkan rasa terbakar pada kulit. Merkuri dalam kadar terkecil dapat bersifat racun, penggunaan dosis tinggi dapat menyebabkan kerusakan permanen otak, ginjal dan gangguan perkembangan janin. Tujuan penelitian ini adalah untuk mengidentifikasi dan menentukan kadar hidroquinon dan merkuri pada krim malam dari beberapa klinik kecantikan di Tangerang. Sampel diambil dari lima klinik kecantikan di daerah Tangerang, Banten. Sampel dianalisis dengan menggunakan HPLC (High Perform Liquid Chromatography) untuk mengetahui kadar hidroquinon, sedangkan kadar merkuri dianalisis dengan menggunakan ICP-MS (Inductively Coupled Plasma Mass Spectrometry). Penelitian ini dilakukan di Laboratorium Kesehatan Daerah Provinsi DKI Jakarta. Hasil penelitian menunjukkan bahwa dari 5 sampel yang dianalisis terdapat 3 sampel positif mengandung Hidroquinon dengan krim B mengandung 4,87% hidroquinon, krim D mengandung 4,64% hidroquinon dan krim E mengandung 5,23% kandungan hidroquinon. Kesimpulan penelitian ini adalah penggunaan bahan hidrokuinon pada krim malam masih banyak ditemukan, dari kelima sampel terdapat tiga positif mengandung hidroquinon yaitu dengan kadar 4,87%, 4,64% dan 5,23%, sedangkan penggunaan bahan merkuri dalam sediaan krim malam negatif pada kelima sampel.

D-r K. D r j a gi n. (Kasan). Die Anamiebehandlung mit grossen Dosen Fe hydrog. red. Die Behandlung wurde in 13 Fallen hypochromer und 3 Fallen hy perchromer Anamien ausgefuhrt. Auf Grund des zur Verfugung stehenden Materials gelang der Verfasser zu folgenden Ergebnissen: 1) Der in Fallen des Verfassers durch Anwendung grosser Dosen Fe hydrog. red. erzielte positive Behandlungseffekt wiest klar auf die wohltatige Heilwirkung des Eisens hin. 2) Die Anamiebehandlung mittels grosser Dosen Fe besitzt einen bedeutenden Vorzug vor der Behandlung mit gewohnlichen Dosen. 3) Bei der Anamiebehandlung mit Eisen ist das Wachstum der Menge des Ha moglobins ein schnelleres, als das der Zahl der Erythrozyten, was zum Steigen des Hamoglobin Indicators fuhrt; in den meisten Fallen mehrt sich die Zahl der Erythrozyten vorwiegend in der Mitte Oder am Ende der Behandlung. 4) Bei positiver Wirkung des Einsens steigt die Zahl der Erythrozyten mit lebendgefarbter Granulation auffalend, besonders 'Stark in der Mitte der Behandlung, und fallt am Ende derselben; die Vergrosserung der Zahl der Erythrozyten mit lebendgefarbter Granulation kann als Indikator fur die positive Wirkung des Eisens dienen. 5) In alien Anamiefallen erhohte sich bei Behandlung mit Eisen die Stabilitat der Erythrozyten da, wo sie gesunken war, oder aber blieb erhoht, falls sie schon vor der Behandlung sich in erhohtem Stande befand. 6) Bei positiver Wirkung des Eisens sank der Bilirubingehalt im Plasma des Blutes in den Fallen, wo er erhoht war, auf die normalen Werte herab. 7) In den meisten Fallen finden wir zum Ende der Eisenbehandlung eine Erhohung des prozentualen Gehalts an Basophilen im Blut. 8) Samtliche mit Eisen behandelten Faile hypochromer Anamien (13) ergaben ein positives Resultat; von den 3 hyperchromen Fallen wurde nur in einem Faile ein positives Resultat erzielt.

Objectives We aimed to evaluate the effects of chronic exposure to bisphenol A (BPA) on atrial fibrillation (AF) occurrence in rats. Methods Twenty-two healthy female Wistar rats were randomized into three groups: Control (no BPA; n=7), BPA (exposed to usual BPA doses; 50 μg/kg/day, 9 weeks; n=7), and hBPA (exposed to high BPA doses; 25 mg/kg/day, 9 weeks; n=8). 24-h ECG monitoring was performed using radiotelemetry ECG devices prior to and after transesophageal atrial pacing. Spontaneous and pacing-induced atrial arrhythmias, autonomic tone, and in vivo an in vitro atrial arrhythmogenicity-related parameters were evaluated. Results All studied parameters were similar between Control and BPA (all p>0.05). However, compared to Control, hBPA presented more atrial premature beats both at baseline (p=0.04) and after pacing (p=0.03), more AF episodes (p Conclusions Chronic exposure to high, but not usual BPA doses induced significant atrial proarrhythmic effects in healthy rats, and this may be at least partially due to BPA-induced vagal hyperactivation. Exposure to high BPA doses, such as that occurring in plastics industry workers, could favor AF occurrence even in the absence of underlying cardiovascular disease.

Objective To study the copy number of genes-components of signaling cascades involved in DNA repair, cell cycle regulation and apoptosis under the influence of high doses of ionizing radiation.Material and Мethods The study was carried out on a culture of H1299 non-small cell lung cancer cells. Cell lines were cultured in a Binder incubator (Germany) for 24 h (at 37 °C, 5% CO2 ), and then the groups were divided into therapeutic and control. The first one was irradiated with a NovalisTx, Varian linear accelerator at doses from 18 to 24 Gy, the second was not exposed to radiation. During the study, we monitored cell viability and evaluated apoptotic activity, then each sample was amplified in two iterations. During the study, cell viability was monitored, apoptotic activity was assessed, and then each sample was amplified in two replicates. The relative copy number of genetic loci was determined by Real-Time qPCR (RT-qPCR).Results When comparing the relative copy number in the genetic loci of the H1299 non-small cell lung cancer cell culture after exposure to a high dose of ionizing radiation, a statistically significant decrease in the relative copy number of the CASP3 and RBBP8 genes was found, which may indicate a decrease in the potential of caspase-mediated tumor repopulation and an increase in the radiosensitivity of tumor cells.Conclusion Exposure to high doses of ionizing radiation leads to a detrimental effect on tumor cells and allows to overcome one of the mechanisms of radioresistance – tumor cell repopulation.

The Princess Alexandra Hospital (PAH) Gamma Knife® Centre of Queensland (GKCoQ) began operations in October of 2015 as a sub‐specialty located within a larger radiation oncology service at PAH. It is uniquely positioned as the only Leksell Gamma Knife® (LGK) treatment unit available in the public hospital system in Australia, and the first and only service in Queensland. The GKCoQ treated the 1000th patient on 23 January 2019. LGK is a non‐invasive alternative to neurosurgery which uses radioactive cobalt sources to treat a variety of intracranial conditions ranging from tumours and metastases to functional disorders. It is a platform for stereotactic radiosurgery, a highly precise form of radiotherapy utilising very high doses to the target while maximally sparing surrounding normal brain. LGK enables patient planning and treatment to be done in one day as an outpatient procedure. This paper will outline our LGK service and provide insight into the expanded role that radiation therapists have within the multidisciplinary team required to deliver radiosurgery in a timely manner. The training programme and radiation licensing pathway that have been established for radiation therapists will also be described.

Background: The same dosing schedule, 1000 SQ-U times three, with one-month intervals, have been evaluated in most trials of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis (AR). The present studies evaluated if a dose escalation in ILIT can enhance the clinical and immunological effects, without compromising safety. Methods: Two randomized double-blind placebo-controlled trials of ILIT for grass pollen-induced AR were performed. The first included 29 patients that had recently ended 3 years of SCIT and the second contained 39 not previously vaccinated patients. An up-dosage of 1000–3000–10,000 (5000 + 5000 with 30 minutes apart) SQ-U with 1 month in between was evaluated. Results: Doses up to 10,000 SQ-U were safe after recent SCIT. The combined symptom-medication scores (CSMS) were reduced by 31% and the grass-specific IgG4 levels in blood were doubled. In ILIT de novo, the two first patients that received active treatment developed serious adverse reactions at 5000 SQ-U. A modified up-dosing schedule; 1000–3000–3000 SQ-U appeared to be safe but failed to improve the CSMS. Flow cytometry analyses showed increased activation of lymph node-derived dendritic but not T cells. Quality of life and nasal provocation response did not improve in any study. Conclusion: Intralymphatic immunotherapy in high doses after SCIT appears to further reduce grass pollen-induced seasonal symptoms and may be considered as an add-on treatment for patients that do not reach full symptom control after SCIT. Up-dosing schedules de novo with three monthly injections that exceeds 3000 SQ-U should be avoided. (Less)

Roxadustat is one of the oral hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) that stimulates erythropoiesis and regulates the genes related to iron metabolism. The treatment of HIF-PHIs is useful compared with that of erythropoietin stimulating agent (ESA) using various instruments and procedures. Few clinical researchers have examined the efficacy and safety of switching treatment from Darbepoetin to Roxadustat in Japanese hemodialysis (HD) patients. However, HIF-PHIs have severe adverse drug reactions, such as thrombotic events. In the present study, we evaluated the lower dose of roxadustat in HD patients receiving high dose of ESA therapy. Eighteen anemic HD patients receiving an ESA, that is,, darbepoetin over 40 μg per week, were enrolled in this study. The treatment of these patients was changed to 20 mg of roxadustat three times weekly for 6 months, after which doses were adjusted to achieve a hemoglobin (Hb) target of 10.0-12.0 g/dL. An increase of 58.1 ± 32.5 mg roxadustat three times weekly increased Hb. It also achieved and then maintained levels within the target range at month 6. Ferritin levels of more than 100 ng/mL or TSAT levels of more than 20% were maintained during the 6-month treatment periods with oral or intravenous iron supplementation. It seems unnecessary to increase the initial dose of roxadustat for patients using high doses of ESA. It is suggested that a reconsideration of the starting dose of roxadustat in Japanese HD patients is needed. (Ikegami General Hospital, Medical Corporation SHOWAKAI、Approval number: 2020-4).

Introdução: Dietas hiperproteicas aumentam a concentração de ureia e ácidos, provenientes do metabolismo das proteínas. Portanto, o uso de altas doses de whey proteins precisa ser verificado frente aos seus efeitos sob a função renal. Objetivo: Avaliar o efeito do consumo de 2 g kg-1 d-1 e 4 g kg-1 d-1 whey proteins sobre marcadores bioquímicos creatinina e ureia após 12 semanas de treinamento resistido em ratos Wistar. Métodos: Amostra composta por 52 ratos Wistar machos alocados em 6 grupos. O protocolo teve duração de 12 semanas de treinamento resistido com suplementação diária de whey proteins. A determinação da concentração dos marcadores bioquímicos foi constituída de leitura em absorbância e equação específica dos parâmetros creatinina e ureia. Resultados: A relação creatinina foi significativamente maior apenas no grupo controle em relação aos grupos suplementados e ao treinado controle. A maior excreção de creatinina de 24h (mg/kg) no grupo treinamento resistido e suplementado em comparação ao treinamento controle demonstra possível efeito do treinamento resistido sobre o aumento da massa muscular associada a dose de 4 g kg-1 d-1. Conclusão: O tratamento de ratos machos Wistar suplementados com whey proteins nas doses de 2 g/kg/dia e 4 g kg-1 d-1 durante 12 semanas não resultou em prejuízo de função renal.