Sustainable design of large wastewater treatment plants considering multi-criteria decision analysis and stakeholders' involvement.

The typical treatment scheme of a large municipal wastewater treatment plant (LWWTP) is almost always the result of design based on technical and economic criteria. Once a threshold in terms of population equivalent (PE) is reached, it is possible that additional sludge thermal treatment might be required. Aspects such as greenhouse gas (GHG) emissions and land use for the construction of the WWTP or the service landfill are considered marginal in current design practice; in a world that requires increasingly attention to the environment, these criteria cannot be ignored when defining the treatment scheme of a LWWTP. With the intent of providing a sustainable approach to design, this study aims to identify the best treatment scheme for a LWWTP with a 720,000 PE size. Methodologically, the study involves the development of an approach based on multi-criteria decision analysis (MCDA). Six alternative treatment schemes were considered; two simplified schemes, without primary sedimentation, with extended aeration activated sludge processes and aerobic sludge stabilization; four full schemes, with primary sedimentation and anaerobic sludge digestion. Some schemes differ for the organic loading rate applied; others for the use of sludge incineration. Subsequently, six evaluation criteria (ECs) such as GHG emissions, electricity consumption, running costs, WWTP planimetric area, surface for the service landfill, as well as WWTP as biorefinery have been considered. The weighting of the ECs involved the participation of the main stakeholders in such a decision-making process, following a bottom-up approach. The resolution of the MCDA problem allowed the identification of the full scheme based on primary sedimentation, biological activated sludge at low organic load (0.210 kgBOD5/kgVSS/d) and anaerobic sludge digestion as the best solution. The sensitivity analysis, able to indirectly take into account the multitude of decision makers involved, allowed corroborating the results. The obtained treatment scheme was different from that generally adopted in current design practice for LWWTPs.

Ejector pin-related high-cycle fatigue fracture of the critical die corner during automatic multistage cold forging of an automotive wheel nut.

An experimental and numerical study on the ejector pin's mechanics during automatic multistage cold forging (AMSCF) of an automobile wheel nut is conducted. The traditional, decoupled die structural analysis method (DDSM) of analyzing die structures as one of the post-processing functions is criticized, which uses the tractions exerting on the die parts predicted from the forging simulation under the rigid die assumption. To cope with the matter of the DDSM, a multibody treatment scheme (MBTS) is proposed to simulate the AMSCF process, emphasizing the ejector pin's mechanics, using an implicit elastoplastic finite element method. The experiments qualitatively validate the finite element predictions. It is shown that the asymmetric sheared material in AMSCF greatly influences the ejector pin's mechanics, which is characterized by its lateral and longitudinal displacements because of its structural flexibility. It is emphasized that the detailed understanding of the ejector pin's mechanics may not only give a helpful connection towards smart manufacturing because of its mechanical flexibility and sensitivity to the excitations and responses, but it also reveals the reason for the die's high-cycle fatigue (HCF) fracture of the critical die corner (CDC) near at the end of the ejector pin.

Corrigendum: A heterozygous mutation in NOTCH3 in a Chinese family with CADASIL.

[This corrects the article DOI: 10.3389/fgene.2022.943117.].

A heterozygous mutation in NOTCH3 in a Chinese family with CADASIL.

Introduction: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal-dominant systemic vascular disease that primarily involves small arteries. Patients with CADASIL experience migraines, recurrent ischemic strokes, cognitive decline, and dementia. The NOTCH3 gene, which is located on chromosome 19p13.12, is one of the disease-causing genes in CADASIL. Herein, we investigate the genetic and phenotypic features in a Chinese CADASIL family with heterozygous NOTCH3 mutation. Methods and Results: In the family, the proband suffered from dizziness, stroke, and cognitive deficits. Brain magnetic resonance imaging (MRI) demonstrated symmetrical white matter lesions in the temporal lobe, outer capsule, lateral ventricle, and deep brain. Whole-exome sequencing identified a known missense mutation in the proband, c.397C>T (p.Arg133Cys), which was identified in his son and granddaughter using Sanger sequencing. The proband's younger brother and younger sister also have a history of cognitive impairment or cerebral infarction, but do not have this genetic mutation, which may highlight the impact of lifestyle on this neurological disease. Conclusion: We identified a known CADASIL-causing mutation NOTCH3 (c.397C>T, p.Arg133Cys) in a Chinese family. The clinical manifestations of mutation carriers in this family are highly heterogeneous, which is likely a common feature for the etiology of different mutations in CADASIL. Molecular genetic analyses are critical for accurate diagnosis, as well as the provision of genetic counselling for CADASIL.

A Preliminary Exploration of the Efficacy of Gentamicin Sponges in the Prevention and Treatment of Wound Infections.

PURPOSE: This study aimed to construct drug-loading and drug-releasing quantitative equations for gentamicin sponges in addition to realizing a gentamicin sponge for wound infection prevention and treatment. METHODS: Sterile sponges were cut into pieces of 1×1 × 0.5 cm and immersed in 40, 16, 8, 4, 1.6, 0.8, or 0 mg/mL of gentamicin solution for 12, 24, 48, 96, or 120 h to evaluate their gentamicin loading. The sponges were subsequently immersed in the gentamicin solution of different concentrations for 48 h, air-dried, and then immersed in 10 mL of 0.9% physiological saline to evaluate the gentamicin release. Methicillin-sensitive Staphylococcus aureus (MSSA) and Pseudomonas aeruginosa were used to explore the sponges' infection prevention scheme. In addition, a rat femur fracture with wound infection model was used to assess the infection treatment scheme. RESULTS: The antibacterial zone sizes of the sponges immersed in 40, 16, 8, 4, 1.6, and 0.8 mg/mL of the gentamicin solution were larger than those of the 0 mg/mL air-dried sponge, and the difference was statistically significant (p < 0.01, p < 0.01, p < 0.01, p < 0.01, p < 0.01, and p < 0.01, respectively). The rats in the 40, 16, and 8 mg/mL air-dried sponge groups had no wound suppuration in either the MSSA or P. aeruginosa rat infection models. CONCLUSION: A quantified equation for the sponges' gentamicin loading and release was achieved with high accuracy. Furthermore, we recommend the 40, 16, or 8 mg/mL air-dried sponge for the treatment of wounds with antibiotic-sensitive bacterial infections.

Romanian clinical guideline for diagnosis and treatment of COPD.

Chronic obstructive pulmonary disease (COPD) is a disease with increasing prevalence and burden for health systems worldwide. Every country collects its own epidemiological data regarding COPD prevalence, morbidity and mortality while taking steps to educate the population and medical community to improve early detection and treatment. The rising COPD prevalence creates a need for comprehensive guidelines. In 2012 and 2017-2018, the Romanian Society of Pneumology (SRP) organised national inquiries for COPD, while lung physicians in Romania began receiving education regarding the correct algorithms for COPD diagnosis and therapy. During 2019, a Romanian clinical guideline for diagnosis and treatment of COPD was published, and a condensed version of key points from this guideline are presented herein. COPD is diagnosed based on the presence of three major components: relevant exposure history, respiratory symptoms, and airway limitation that is not fully reversible. Clinical evaluation of patients diagnosed with COPD should include the level of symptoms, exacerbation rate, the presence of comorbidities and determination of phenotypes. The present abridged guideline is designed to be accessible and practical for assessing and managing patients with COPD. The application of up-to-date COPD guidelines may enhance the optimism of physicians and patients in managing this disease.

Treatment of cork boiling wastewater using a horizontal subsurface flow constructed wetland combined with ozonation.

Cork boiling wastewaters (CBW) are strongly coloured complex aqueous solutions with high organic load of biorecalcitrant and toxic nature. The feasibility and efficiency of a CBW treatment process combining ozonation as pre- and post-treatment of a horizontal subsurface flow constructed wetland (HSFCW) was assessed. Over an extended monitoring period of 390 days, two lab-scale HSFCW units were tested; one planted with P. australis (CWP) and one unplanted-control (CWC) operated at average organic loads rates (OLR) of 5 and 10 g COD/m2/d. CWP always outperformed the control unit. The ozonation trials were run at pH values of 8.15-8.21 and 5.39-5.45 (without adjustment) at ozone to COD ratios of 0.25-0.29 and 0.24-0.59 when implemented as pre- and post-treatment, respectively. Average removals (calculated through mass balance basis) were 78-88%, 86-91%, 71-89% and 43-89% for COD, BOD5, Total Phenols (TPh) and colour when ozonation was implemented as post-treatment. For ozonation as pre-treatment, respective figures were 77-80%, 79-92%, 78-85% and 19-73%. Regardless of the treatment scheme and OLR, ozonation was very effective in biodegradability increase (i.e., BOD5/COD) from 0.18 to 0.42 when applied as pre-treatment, and decolourization after the HSFCW increased from 21% to 91% (post-treatment) with respective ozone consumed yields of 67-69% and 72-85%. The best results were obtained for the scheme CWP + Ozonation at OLR of 5.33 g COD/m2/d with COD reductions from 1950 mg/L to 81-88 mg/L in the effluent and TPh from 125 mg/L to 5-6 mg/L at limited ozone amounts of 0.21-0.45 g O3/m2/d.

Nanotechnology-based sorption and membrane technologies for the treatment of petroleum-based pollutants in natural ecosystems and wastewater streams.

Petroleum processing wastewater (PPW) is a complex mixture of free, soluble, and emulsive hydrocarbons that often contain heavy metals and/or solid particles. As these hazardous constituents can accumulate in human beings and the environment, exposure to the PPW can have harmful effects in various respects. The use of environmental nanotechnologies (E-Nano) is considered an attractive option to resolve the problems associated with PPW. Among different treatment technologies, E-Nano-based sorption (adsorption/absorption) and membrane filtration approaches have been proven to have outstanding efficacy in remediation of PPW pollutants. It is, however, crucial to determine the appropriate technological option (e.g., low-cost operational conditions) for the practical application of such technologies. In this review, the potential of E-Nano-based sorption and membrane technologies in the treatment of various PPW pollutants is discussed based on their performances in comparison to traditional technologies. Their suitability is evaluated further in relation to their merits/disadvantages and economic feasibility with the goal of constructing a perspective map to efficiently implement the E-Nano technologies.

Multidosing Intramuscular Administration of Methotrexate in Interstitial Pregnancy With Very High Levels of ß-hCG: A Case Report and Review of the Literature.

Ectopic pregnancy (EP) is the implantation of an embryo outside the endometrial cavity of the uterus. Signs and symptoms of EP may arise between the 6th and the 8th week of gestation and include vaginal bleeding, lower abdominal and pelvic pain. Frequently EPs implant in the fallopian tubes. A rare EP is the interstitial pregnancy, a life-threatening condition being responsible for nearly 20% of all deaths caused by EPs. Because of its unique location, the diagnosis is difficult and based on signs and specific criteria together with measuring of serum ß-hCG. Usually, EP is treated by surgical approach, which is associated with increased morbidity, decreased fertility and increased likelihood of hysterectomy and uterine rupture in a subsequent pregnancy. Early diagnosis is crucial to life saving and allowing alternative therapeutic interventions such as pharmacological treatments. Methotrexate (MTX) represents the mainstay therapy. There is no standard care for the interstitial pregnancy for what concerns either surgical or pharmacological approaches. We reported a case of a 36-year-old woman admitted to the Hospital of Salerno-Italy with a value of serum ß-hCG of 35,993 IU/L. Transvaginal ultrasonography revealed an empty uterine cavity and a mass of 35.7 mm in diameter characterized by a hypoechoic central area. The patient was in stable haemodynamic condition and no haematologic, renal and hepatic impairments were recorded. Despite the high serum ß-hCG levels, a pharmacological approach was preferred to a surgical one. The patient was treated with intramuscular administration of MTX in daily dose of 1 mg/Kg alternated with 0.1 mg/kg folinic acid for 5 days. The patient remained hospitalized for 20 days and no side effects were reported. The decrease of the serum ß-hCG was monitored and more than 15% reduction was detected between the 4th and the 7th day after the beginning of the treatment. The serum ß-hCG became undetectable 35 days after. A multidosing intramuscular administration of MTX was effective and safe even in the presence of very high serum ß-hCG levels. Together with similar cases reported in literature, the present results can contribute to improve the decision making in the treatment of the interstitial pregnancy.

Novel strategies for the treatment of asthma.

Novel treatment strategies are currently emerging for patients with inadequately controlled asthma despite good adherence and trigger avoidance. These strategies serve primarily to reduce or completely avoid long-term oral corticosteroid therapy. A number of these options have already been implemented in practice or will soon be authorized for the treatment of asthma, while others still need to prove their clinical practicability, safety and efficacy. The present article provides an overview of the broad spectrum of novel inhaled, oral, systemic, and invasive treatment strategies for asthma.

Hospital and patient influencing factors of treatment schemes given to type 2 diabetes mellitus inpatients in Inner Mongolia, China.

BACKGROUND: In clinical practice, the physician's treatment decision making is influenced by many factors besides the patient's clinical conditions and is the fundamental cause of healthcare inequity and discrimination in healthcare settings. Type 2 diabetes mellitus (T2DM) is a chronic disease with high prevalence, long average length of stay and high hospitalization rate. Although the treatment of T2DM is well guideline driven, there is a large body of evidence showing the existence of treatment disparities. More empirical studies from the provider side are needed to determine if non-clinical factors influence physician's treatment choices. OBJECTIVE: To determine the hospital and patient influencing factors of treatment schemes given to T2DM inpatients in Inner Mongolia, China. METHODS: A cross-sectional, hospital-based survey using a cluster sampling technique was conducted in three tertiary hospitals and three county hospitals in Inner Mongolia, China. Treatment schemes were categorized as lifestyle management, oral therapy or insulin therapy according to the national guideline. Socio-demographic characteristics and variables related to severity of disease at the individual level and hospital level were collected. Weighted multinomial logistic regression models were used to determine influencing factors of treatment schemes. RESULTS: Regardless of patients' clinical conditions and health insurance types, both hospital and patient level variables were associated with treatment schemes. Males were more likely to be given oral therapy (RRR=1.72, 95% CI=1.06-2.81) and insulin therapy (RRR=1.94, 95% CI=1.29-2.91) compared to females who were given lifestyle management more frequently. Compared to the western region, hospitals in the central regions of Inner Mongolia were less likely to prescribe T2DM patients oral therapy (RRR = 0.18, 95% CI=0.05-0.61) and insulin therapy (RRR = 0.20, 95% CI=0.06-0.67) than lifestyle management. Compared with non-reformed tertiary hospitals, reformed tertiary hospitals and county hospitals were less likely to give T2DM patients oral therapy (RRR = 0.07 and 0.1 respectively) and insulin therapy (RRR = 0.11 and 0.17 respectively). CONCLUSION: Gender was the only socio-demographic factors associated with treatment scheme for T2DM patients. Hospitals from different regions have different T2DM treatment patterns. Implementation of reform was shown to be associated with controlling medication use for T2DM inpatients. Further studies are needed to investigate the causes of unreasonable treatment disparities so that policies can be generated accordingly.

Discussing Differences of Different Traditional Chinese Medicine Schemes of COVID-19 Based on Principle of "Treatment in Accordance with Three Categories of Etiologic Factors" / 中国实验方剂学杂志

Since the outbreak of corona virus disease-2019 (COVID-19), the timely intervention of Chinese medicine has played an important role， it can significantly improve the clinical symptoms of patients, alleviate fever, cough, shorten the course of disease and reduce the conversion rate of mild disease to severe disease， moreover, it has obvious advantages in improving survival rate, prognosis and quality of life in patients. In order to make better use of the therapeutic effect of Chinese medicine and overcome the epidemic situation as soon as possible, various provinces, municipalities and autonomous regions have introduced local Chinese medicine treatment schemes in accordance with the geography, climate and epidemic situation. In this article, we have analyzed the similarities and differences among treatment schemes from the perspective of three factors, and it is believed that the onset season is the same for this disease, and the differences between treatment schemes mainly depend on geographical and climatic factors. The results showed that in seven regions of China, the early symptoms in warm and humid regions such as Central China, South China, East China and Southwest China were characterized by "wet, warm, hot, and toxic", and treatment schemes mainly adopted the recipes with clearing heat and detoxifying, strengthening spleen and removing dampness functions. The early symptoms in cold regions such as Northeast China, North China, and Northwest China were mostly characterized by "cold, wet, wind, and toxic", and the therapeutic recipes emphasized on the effects of expelling wind and cold, removing toxicity and dampness. Among them, the national plan with the Hubei epidemic situation as an important reference has gradually evolved from a single syndrome attribute of each period to both cold and hot syndromes with multiple treatment methods. With the development of the disease, epidemic toxin and toxic heat in the lungs are the main characteristics in the medium term, when the treatment mainly focuses on purging heat and removing toxins. In severe cases and advanced stage, internal block and outward desertion are the main symptoms, when the treatment mainly focuses on block dredging and relieving desertion. In the recovery period, deficiency of lung and spleen Qi, and deficiency of Qi and Yin are the main symptoms, when the treatment is mainly used to invigorate the spleen, tonify the lungs, and nourish Qi and Yin. The physical factors are mostly reflected in the prevention program, so they are rarely mentioned in the treatment program. The Chinese medicine treatment schemes of COVID-19 in different regions show obvious differences. It is of great significance to analyze these differences and sum up the corresponding laws for the differential prevention and treatment of infectious diseases like COVID-19.

Analysis on diagnosis and treatment scheme of traditional Chinese medicine in treatment of COVID-19 in Chinese provinces and regions / 中草药

Since December 2019, a novel coronavirus-infected pneumonia was first detected in Wuhan, such cases had been subsequently discovered in other cities. The disease caused by the novel coronavirus was officially named COVID -19 (coronavirus disease 2019) by the world health organization. National Health Commission of China and other provinces and cities have successively performed syndrome differentiation of COVID-19 and provided corresponding Chinese medicine treatment programs. In this epidemic, the disease is a “dampness toxin”. The best principle for treatment is early detection and early treatment. Both Chinese and Western medicine have their own advantages. The advantages could be complementary and could not be replaced each other. Therefore, we collected the Chinese medicine treatment programs for the treatment of COVID-19 comprehensively, conducted a systematic analysis, and especially analyzed the pharmacological basis of traditional Chinese medicine for the treatment of COVID-19, which provided a basis for the rationality of Chinese medicine prescription for the treatment of COVID-19, and provided a reference of updating the diagnosis and treatment plan for provinces and cities.