Biochemical consequences of glucocerebrosidase 1 mutations in Parkinson’s disease

Parkinson’s disease(PD,OMIM#168600)is a common neurodegenerative disorder with a global prevalence of approximately 8.5 million.PD is characterized by four cardinal motor symptoms:bradykinesia,rigidity,resting tremor,and subsequently by postural instability.It usually involves non-motor symptoms such as rapid eye movement sleep disorder,dementia,anosmia,and autonomic dysfunction.The gene glucocerebrosidase 1(GBA1),which encodes the lysosomal enzyme glucocerebrosidase(GCase)(IUBMB:EC 3.2.1.45),shows strong linkage with PD;variants of GBA1 are the commonest genetic association with PD(Sidransky et al.,2009).Several mechanisms may underlie the relationship between GBA1 mutations/variants and the molecular pathology of PD(Figure 1A and B).

Neurological consequences of human calmodulin mutations

When calcium ions enter the cytosol,it is a stimulatory signal for cellular events.The calcium sensor calmodulin picks up the change in calcium concentration and relays this information to its more than 300 downstream interaction partners.In this way,calmodulin affects cellular processes such as fertilization,muscle contraction,neuronal firing,and apoptosis.That is,calmodulin is involved in(nearly)everything!The significance of calmodulin is emphasized by the fact that we all carry three different genes(CALM1,2,3)on different chromosomes that encode the exact same calmodulin protein,and these are all expressed in all cell types.Moreover,throughout vertebrate evolution,the protein sequence has remained completely unchanged.

Tau's function and dysfunction in the brain:when small changes have big consequences

With the increase of life expectancy and population growth,neurodegenerative diseases have risen too and are projected to be a major health public concern by 2050.Neurodegenerative diseases are characterized by the progressive decline of cognitive function leading to the subsequent loss of autonomy.Although the underlying causes of neurodegeneration are not well understood,aging is the main risk factor.

Lactate is a potentially harmful substitute for brain glucose fuel:consequences for metabolic restoration of neurotransmission

The metabolite lactate (L-lactate) can be generated and released by diverse brain cells,including neurons,astrocytes,and oligodendrocytes (Kann,2023;Rae et al.,2024).Lactate production usually requires the degradation of glucose (D-glucose)-and glycogen in astrocytes-to pyruvate by glycolysis and subsequent conversion of pyruvate to lactate by the enzyme lactate dehydrogenase(Figure 1A;Dienel,2019;Rae et al.,2024).

Associated Factors and Consequences of Uterine Fibroids in Hospitals in the Borgou Department of Benin in 2022

Introduction: Uterine fibroids are the most common gynecological tumors in women of childbearing age and have multiple clinical manifestations. Objective: To determine factors associated with uterine fibroids in the Borgou department of Benin in 2022. Method: Descriptive, analytical cross-sectional study from August 22 to September 22, 2022. The sample consisted of women consulting for gynecological problems in 6 hospitals in the Borgou department in the North of Benin. Results: Of the 744 women surveyed, 10.1% were diagnosed with uterine fibroids. Women with uterine fibroids were often married, paucigesture, and nulliparous. Their main reasons for consultation were the desire for motherhood (50.7%), pelvic pain (46.7%), and genital hemorrhage (14.7%). Age, history of miscarriage, high blood pressure, and diabetes were significantly associated with the presence of uterine fibroids (Conclusion: Uterine fibroids are common in hospitals in northern Benin. There were factors associated with them that should be taken into account in management strategies.

Accident source term and radiological consequences of a small modular reactor

Considering the growing global demand for energy and the need for countries to achieve climate goals,there is an increasing global interest in small modular reactors(SMRs)and their applications.Accident source term and radiological consequence evaluations of SMRs are key components of nuclear and radiation safety reviews,which affect the site,exclusion area(EAB),and low population zone outer boundaries.Based on the design characteristics of the SMR and accident analysis results,a theoretical model of a whole-core fuel cladding damage accident was constructed to study the radioactivity released into the environment and its consequences.The accident source term and radiation dose calculation models were established to analyze the released amounts of radionuclides and the total effective dose affecting individuals at the site boundary.The results showed that the amount of radionuclides released into the environment after a whole-core fuel cladding damage accident reached 10^(14) Bq,among which the release amount of ^(133)Xe was the largest.The total effective dose at the site boundary 30 days after the accident was 8.65 mSv.The highest total effective dose affecting individuals occurred to the east-north-east.The results of the accident source term and radiological consequence provide technical support for site boundary dose assessments and reviews of SMRs.

Empowering women to combat osteoporosis:unveiling the causes,consequences,and control strategies

Osteoporosis is a common bone disease in women worldwide, leading to decreased bone density and an accelerated risk of fractures. The causes of osteoporosis in women include age (senile osteoporosis), menopause-associated hormonal changes, deficiencies in calcium and vitamin D, genetics, lifestyle factors, medical conditions, and some type of medications. The consequences of osteoporosis are colossal, consisting of fractures, decreased quality of life, psychological impacts, and economic burden. To effectively control the menace of osteoporosis in women, numerous strategies are advocated. Adequate calcium and vitamin D consumption through diet or supplements is vital. Regular weight-bearing activities and strength training that promote bone density. Maintaining a healthy life-style through avoiding smoking, limiting alcohol in-take and maintaining a wholesome body weight is essential. Hormone replacement therapy and some medications may be recommended in certain cases. Early detection through regular bone density and blood tests is crucial to lowering its impact. Creating a supportive network through educational programs and resources fosters awareness and empowerment. By engaging these strategies, women can be empowered to combat osteoporosis, reduce fracture risk, and build stronger bones for their overall well-being.

Risk factors and long-term health consequences of macrosomia:a prospective study in Jiangsu Province,China

We sought to determine risk factors associated with fetal macrosomia and to explore the long-term consequence of infant macrosomia at the age of 7 years.A prospective population based cohort study was designed to examine the associations between maternal and perinatal characteristics and the risk of macrosomia.A nested case-control study was conducted to explore the long-term health consequence of infant macrosomia.The mean maternal age of the macrosomia group was 24.74±3.32 years,which is slightly older than that in the control group（24.35±3.14 years,P = 0.000）.The mean maternal body mass index（BMI） at early pregnancy was 22.75±2.81 kg/m 2,which was also higher than that in the control group（21.76±2.59 kg/m 2,P = 0.000）.About 64.6% of macrosomic neonates were males,compared with 51.0% in the control group（P = 0.000）.Compared with women with normal weight（BMI：18.5-23.9 kg/m 2）,women who were overweight（BMI：24-27.9 kg/m 2） or obese（BMI ≥ 28 kg/m 2）,respectively,had a 1.69-fold（P = 0.000） and a 1.49-fold（P = 0.000） increased risks of having a neonate with macrosomia,while light weight（BMI〈18.5 kg/m 2） women had an approximately 50% reduction of the risk.Furthermore,macrosomia infant had a 1.52-fold and 1.50-fold risk,respectively,of developing overweight or obesity at the age of 7 years（P = 0.001 and P = 0.000）.Older maternal age,higher maternal BMI at early pregnancy and male gender were independent risk factors of macrosomia.Macrosomic infant was associated with an increased predisposition to develop overweight or obesity at the beginning of their childhood.

Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome:a 15-year follow-up from a prospective cohort study

The most severe sequelae after rehabilitation from SARS are femoral head necrosis and pulmonary fibrosis. We performed a 15-year follow-up on the lung and bone conditions of SARS patients. We evaluated the recovery from lung damage and femoral head necrosis in an observational cohort study of SARS patients using pulmonary CT scans, hip joint MRI examinations, pulmonary function tests and hip joint function questionnaires. Eighty medical staff contracted SARS in 2003. Two patients died of SARS, and78 were enrolled in this study from August 2003 to March 2018. Seventy-one patients completed the 15-year follow-up. The percentage of pulmonary lesions on CT scans diminished from 2003(9.40 ± 7.83)% to 2004(3.20 ± 4.78)%(P < 0.001) and remained stable thereafter until 2018(4.60 ± 6.37)%. Between 2006 and 2018, the proportion of patients with interstitial changes who had improved pulmonary function was lower than that of patients without lesions, as demonstrated by the one-second ratio(FEV1/FVC%, t = 2.21, P = 0.04) and mid-flow of maximum expiration(FEF25%–75%, t = 2.76, P = 0.01). The volume of femoral head necrosis decreased significantly from 2003(38.83 ± 21.01)% to 2005(30.38 ± 20.23)%(P = 0.000 2), then declined slowly from 2005 to 2013(28.99 ± 20.59)% and plateaued until 2018(25.52 ± 15.51)%. Pulmonary interstitial damage and functional decline caused by SARS mostly recovered, with a greater extent of recovery within 2 years after rehabilitation. Femoral head necrosis induced by large doses of steroid pulse therapy in SARS patients was not progressive and was partially reversible.

Assessing the impacts of climate change on water resources of a West African trans-boundary river basin and its environmental consequences (Senegal River Basin)

The Senegal River Basin （SRB） is a shared watershed in West Africa which includes regions （the upper basin, valley, and delta）, characterized by distinct environmental conditions. An important feature of the Senegal River flow volume historically was its in- ter-annual irregularity, which caused a major water resource constrain. This situation has been accentuated during the long-term drought （1969-1984） in the Sahel zone which highlights the vulnerability of food-producing systems to climate change and variability. SRB is undergoing fundamental environmental, hydrologic, and socioeconomic traxisitions and represents a good illustration of sensi- tivity to climatic variations and opportunities for adaptation. This paper aims to study water resources systems under stress from cfi- mate variability and change in the Senegal River Basin. The results show （1） through the compilation of available data, information and knowledge （sedimentological, climatical, geological, environmental, archeological, etc.）, the chronological consequences of cli- mate change during the past millennium in West Africa, and also （2） an analysis of the recent impacts and vulnerability to climate change in the SRB and finally （3） the adaptation strategies in the SRB in order to identify and resolve problems associated with this water scarcity and to address the potential for guaranteed agricultural production in this narrow geographic area.

Neurological consequences of systemic inflammation in the premature neonate

Despite substantial progress in neonatal care over the past two decades leading to improved survival of extremely premature infants, extreme prematurity continues to be associated with long term neurodevelopmental impairments. Cerebral white matter injury is the predominant form of insult in preterm brain leading to adverse neurological consequences. Such brain injury pattern and unfavorable neurologic sequelae is commonly encountered in premature infants exposed to systemic inflammatory states such as clinical or culture proven sepsis with or without evidence of meningitis, prolonged mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis. Underlying mechanisms may include cytokine mediated processes without direct entry of pathogens into the brain, developmental differences in immune response and complex neurovascular barrier system that play a critical role in regulating the cerebral response to various systemic inflammatory insults in premature infants. Understanding of these pathologic mechanisms and clinical correlates of such injury based on serum biomarkers or brain imaging findings on magnetic resonance imaging will pave way for future research and translational therapeutic opportunities for the developing brain.

The role of degenerative pathways in the development of irreversible consequences after brain ischemia

Ischemic stroke and irreversible consequences:Ischemic stroke in humans is the second most common cause of death in the world(Mozaffarian et al.,2016).The outcomes after a stroke are often dependent on complications,including motor disorders,depression and dementia(Pluta et al.,2018a),which causes a high risk of re-hospitalization and/or palliative care.This is also the main reason for long-term disability in people after stroke,with up to half of those who survived the stroke will not regain their independence until the end of their lives(Mozaffarian et al.,2016).According to epidemiological forecasts,human ischemic stroke will soon become the dominant cause of death worldwide(Bejot et al.,2016)as well as dementia with the phenotype of Alzheimer’s disease(AD;Kim and Lee 2018).It is suggested that human ischemic stroke and experimental brain ischemia in animals are associated with the possible development of AD neuropathology(Pluta et al.,2018a).

A dynamic food-chain model and program for predicting the consequences of nuclear accident

A dynamic food chain model and program, DYFOM 95, for predicting the radiological consequences of nuclear accident has been developed, which is not only suitable to the West food chain but also to Chinese food chain. The following processes, caused by accident release which will make an impact on radionuclide concentration in the edible parts of vegetable were considered: dry and wet deposition interception and initial retention, translocation, percolation, root uptake and tillage. Activity intake rate of animals, effects of processing and activity intake of human through ingestion pathway ware also considered in calculations. The effects of leaf area index LAI of vegetable were considered in dry deposition model. A method for calculating the contribution of rain with different period and different intensity to total wet deposition was established. The program contains 1 main code and 5 sub codes to calculate dry and wet deposition on surface of vegetable and soil, translocation of nuclides in vegetable, nuclide concentration in the edible parts of vegetable and in animal products and activity intake of human and so on.

Genomic consequences of apple improvement

The apple(Malus domestica)is one of the world's most commercially important perennial crops and its improvement has been the focus of human effort for thousands of years.Here,we genetically characterise over 1000 apple accessions from the United States Department of Agriculture(USDA)germplasm collection using over 30,000 singlenucleotide polymorphisms(SNPs).We con fi rm the close genetic relationship between modern apple cultivars and their primary progenitor species,Malus sieversii from Central Asia,and fi nd that cider apples derive more of their ancestry from the European crabapple,Malus sylvestris,than do dessert apples.We determine that most of the USDA collection is a large complex pedigree:over half of the collection is interconnected by a series of fi rst-degree relationships.In addition,15%of the accessions have a fi rst-degree relationship with one of the top 8 cultivars produced in the USA.With the exception of‘Honeycrisp',the top 8 cultivars are interconnected to each other via pedigree relationships.The cultivars‘Golden Delicious'and‘Red Delicious'were found to have over 60 fi rst-degree relatives,consistent with their repeated use by apple breeders.We detected a signature of intense selection for red skin and provide evidence that breeders also selected for increased fi rmness.Our results suggest that Americans are eating apples largely from a single family tree and that the apple's future improvement will bene fi t from increased exploitation of its tremendous natural genetic diversity.

Environmental Consequences of Oil Spills on Marine Habitats and the Mitigating Measures—The Niger Delta Perspective

The Niger Delta region has witnessed environmental impacts arising from oil production activities. Soil fertility in these areas and the entire marine habitat was investigated based on the re-occurring spill incidents in the area to establish the consequences of oil pollution on key performance indicators as well as the remedial actions for resuscitation. One of the bases of evaluation was on the fertility profile of the area impacted by oil spills as compared with the areas without oil spills influence. A suitable cost effective and environmentally friendly technique to handle the pollutions in the Niger Delta region can be found in systematic containment, recovery, clean up and restoration of the marine habitat to its initial capacity and status to be able to sustain life once again.

Psychological Consequences of COVID-19 and Challenges forPost-traumatic Interventions

This article reviewed the psychological consequences of the novel coronavirus disease COVID-19 and the challenges that face post-traumatic interventions.The outbreak of the virus,the daily deaths and quarantine procedures resulted in several mental health problems and the need for psychological interventions was increasingly highlighted in different studies.Not only the patients but those who are in the frontline like physicians and nurses need psychological services as well.The infected people suffer from fear of death,similarly the quarantined people are afraid of infection and suffer also from social isolation,loneliness,anger,depression,anxiety and stress.The most common troubles resulted from the outbreak of COVID-19 are sleep disorders,overprotection measures,feeling helplessness,emotional problems,worry about health,sadness and frustration.There are different challenges of post-traumatic interventions,take for example,shortage of professional psychiatrists and experienced psychologists,lack of training on psychological skills to deal with patients’anxiety,panic,and other emotional problems and unwillingness to be quarantined and lack of cooperation in remedial measures.Future studies should adopt interview and self-reported questionnaire to get a deeper insight into the Psychiatric and Psychological disorders associated with the epidemic.Finally,post-traumatic interventions should focus on improving coping strategies and reducing mental health problems.

Legal Consequences of the Separation of the Chagos Archipelago from Mauritius in 1965

The Court finds that the process of decolonization of Mauritius was not lawfully completed when that country acceded to independence and that the United Kingdom is under an obligation to bring to an end its administration of the Chagos Archipelago as rapidly as possible THE HAGUE, 25 February 2019.

Consequences of redefining Alzheimer＇s disease in terms of amyloid burden without regard to cognitive decline

Alzheimer＇s disease（AD）redefined：For the past century,AD has been defined as a disease of progressive cognitive decline paired with a burden of amyloid-β（Aβ）plaques and pathologic tau tangles in the hippocampus and forebrain.However,a recent Framework paper jointly sponsored by the National Institute on Aging and the Alzheimer＇s Association（Jack et al.,2018）proposes new classification guidelines for AD,which,if adopted,will have profoundconsequences for the future management of AD.

Relationship between variation of HBV preS function domains and clinical consequences of HBV infection

Objective:To investigate the relationship between variation of HBV preS genes and clinical consequencesof HBV infection. Methods: We selected 3 groups (3 in each) of HBV infected individuals including those of acuteinfection with complete recovery, chronic HBV carriers and chronic severe hepatitis B. The preS genes were amplified from serum samples with half nested PCR. The PCR products were cloned into M13 vectors and 10 cloneswere randomly selected for each individual and sequenced with standard methods. A total of 90 clones were sequenced and analyzed by DNA homological comparison. Results: The characteristics of the preS genes were significantly different in HBV-infected individuals with different clinical consequences.①As for acute hepatitis B, thepreS function domains were stable and no changes in epitopes for T and B cells were found. ②For chronic HBVcarriers, the function domains within preS proteins showed potentially changes with epitope drifts of T and B cellsbecause of the high variation of HBV preS genes. ③For chronic severe hepatitis B, there were special changes inthe function domains of B cells. The abnormally high immune response would cause severe liver injury in these individuals. Conclusion: This study provides experimental evidence for researches about the possible association ofvariation of preS1/S2 functional regions with clinical consequences.

Toward a better understanding of cascading consequences of atmospheric reactive nitrogen along its transport pathway

Over the past century,the creation of nitrogenous fertilizer has sustained food production and thereby the global population.Nevertheless,all the nitrogen used in food production is added to the environment,as is the nitrogen emitted to the atmosphere during fossil-fuel combustion(Gruber and Galloway 2008).Of particular concern is the consequence of large reactive nitrogen leaking from the‘nitrogen cascade’,especially ammonia and nitrogen oxides,which can first cause air pollution and then,after it has been transported to remote areas and deposited on the ground,lead to soil acidification,water eutrophication and biodiversity loss(Galloway et al.2003).