IRF2BP2 mutation with autoimmune enteropathy, immune deficiency, and respiratory failure

Case history: We present the case of a 31-year-old Hispanic male with history of recurrent bronchiectasis, invasive aspergillosis, and severe persistent asthma, who is now status post lung transplant for end-stage lung disease. He initially presented at 7 years of age with diarrhea, failure to thrive, and nearly absent immunoglobulin levels (IgG < 33 mg/dL, IgA < 7 mg/dL, IgM = 11 mg/dL, IgE = 4 IU/dL) necessitating IVIG treatment. Small intestinal biopsy showed villous atrophy consistent with autoimmune enteropathy. Sweat chloride was reported as indeterminate (44 me/dL). Initial WBC, platelet, and T- and NK-cell counts were within normal range, and B-cell count and percentage were borderline low. Most recently, he was found to have increased immature B-cell count (CD21low), decreased memory B-cells, and poor pneumococcal vaccine antibody response. Patient has been hospitalized numerous times with increasingly severe bronchiectasis, pneumonitis, and COVID-19 infections twice despite vaccination, leading to respiratory failure and lung transplantation. Family history is negative for immune deficiency and lung diseases. Discussion(s): Of these 3 VUSs (see the table), the one in IRF2BP2 has the most pathogenic potential due to its autosomal dominant inheritance, its location in a conserved domain (Ring), and previous case reports of pathogenic variants at the same or adjacent alleles 1-3. Baxter et al reported a de novo truncating mutation in IRF2BP2 at codon 536 (c.1606CinsTTT), which is similar to our patient's mutation. This patient was noted to have an IPEX-like presentation, with chronic diarrhea, hypogammaglobulinemia, and recurrent infections. Variant Functional Prediction Score for our variant predicts a potentially high damage effect. There are 2 other case reports of heterozygous mutations in loci adjacent to this allele;one (c.1652G>A)2 with a similar clinical phenotype to our patient and the other (C.625-665 del)3 with primarily inflammatory features and few infections. Impact: This case highlights a variant in IRF2BP2 associated with severe hypogammaglobulinemia, recurrent pulmonary infections, and autoimmune enteropathy. [Table presented]Copyright © 2023 Elsevier Inc.

Inheritance and innovation: maintain academic communications in microsurgery under the normalized prevention and control of COVID-19 pandemics.

Chinese Journal of Microsurgery, based on the premise of doing well in the prevention and control of COVID-19 pandemics, shall keep on driving on the inheritance and innovation, carry forward the spirit of microsurgery, give full play to the advantages of microsurgery technology and improve the level of surgical repair and reconstruction, as well as try new ways for academic communications and give full play to the roles of an academic platform for a professional magazine;Clinical Orthopaedic Microsurgery (internal communication), the internal journal of editorial office, is the "showcase in China" to highlight and disseminate the achievements in microsurgery, focus on the support for the Chinese young microsurgeons who work in the front-line of medical services, provide a platform effectively for the young microsurgeons in China to actively participate in the Sino-English literary exchange, and truly "publish the papers on the land of our motherland".Copyright © 2022 by the authors.

Experiences of patients from minority ethnic backgrounds in the stem cell transplant pathway during COVID-19

Background: Stem cell transplantation is a potentially life-saving intervention for patients with blood cancer. Research suggests that there are existing disparities in access, care and treatment experiences, with patients identifying with a minority ethnic heritage reporting greater disadvantage compared to patients from white British, Irish or Northern European backgrounds. Although we know that the COVID-19 pandemic has been challenging for patients, less is known about the experiences of patients from specific ethnic communities. Method(s): In this research, we undertook 1-1, semi-structured interviews with eight patients within the stem cell transplant pathway who identify with a minority ethnic background. Interviews took place online, between May and November 2021. The interview questions explored views on aspects of the pandemic, including access and experience of care delivery, intervention, mental health and financial impact. Interviews were transcribed verbatim and analysed using reflexive thematic analysis. Result(s): The majority of patient participants were female (75%), and identified with a Black African or Caribbean heritage (75%). Four themes were identified from the data: (1) 'Lack of suitable donors' described the challenges of finding a stem cell donor and the importance of raising awareness of stem cell donation specifically within minority ethnic communities;(2) 'Experiences of care' explored patients' experiences of the healthcare system from pre-diagnosis to post-treatment, including how the COVID-19 pandemic had made some aspects of care easier but acted to disrupt others;(3) 'Intense and unpredictable process' described the nature of living with blood cancer and how this has impacted upon patients' lives including the extent to which they had been able to access and make use of advice to help keep them safe during the pandemic;and (4) 'Coping mechanisms' identified the factors which helped patients' to understand and adjust to living with their diagnosis and the treatment process. Conclusion(s): Patients in the stem cell transplant pathway often experience intense treatment regimens, debilitating symptoms and long hospital stays, which has a significant impact on their lives. Minority ethnic patients describe facing additional challenges in relation to health inequalities both within and outside of the pandemic. Seeking support from family, peers or community organisations can help buffer the negative impacts of living with blood cancer and multiple disadvantages, but such support was more difficult to access during the pandemic. This had psychological consequences for patients who are already within an intense emotional journey. Pandemic recovery plans should address mental health support as a priority.

An epigenetic synopsis of parental substance use.

The rate of substance use is rising, especially among reproductive-age individuals. Emerging evidence suggests that paternal pre-conception and maternal prenatal substance use may alter offspring epigenetic regulation (changes to gene expression without modifying DNA) and outcomes later in life, including neurodevelopment and mental health. However, relatively little is known due to the complexities and limitations of existing studies, making causal interpretations challenging. This review examines the contributions and influence of parental substance use on the gametes and potential transmissibility to the offspring's epigenome as possible areas to target public health warnings and healthcare provider counseling of individuals or couples in the pre-conception and prenatal periods to ultimately mitigate short- and long-term offspring morbidity and mortality.

More people, especially those of reproductive age, are using substances, and there is growing evidence to suggest that parental substance use before and during pregnancy may adversely affect offspring and result in issues later in life, including mental health challenges. Such relationships have been demonstrated with nicotine, alcohol, cannabis, opioids and illegal drugs (e.g., heroin, cocaine, methamphetamines). Some of these adverse impacts on offspring can potentially be passed down in families even after parents have quit using the substance. Because more individuals are using drugs, especially during the COVID-19 pandemic, it is important that families learn more about the potential impact of substance use on their future offspring before they try to get pregnant.

Aplasia cutis congenita in dizygotic twin infants

Aplasia cutis congenita (ACC) is often sporadic, but familial cases have been reported. We report a case of a dichorionic diamniotic twin pregnancy in which both the male and female twins had matching areas of aplasia cutis on their scalps. An Irish couple sought fertility treatment using a donor egg and paternal sperm. Successful in vitro fertilization (IVF) and the transfer of two embryos resulted in a diamniotic dichorionic twin pregnancy. Two fetal poles were noted at the 12-week ultrasound (US) scans. The mother suffered from a minor urinary tract infection during the first trimester but had no other history of infection, including herpes simplex virus or COVID- 19. She was known to be varicella immune prior to pregnancy. The twins were born by elective caesarean section owing to breech presentation. Twin one was female and twin two was male. Both infants were born with scarring on the crown of their head, which was consistent with ACC. Cranial US showed no underlying bony abnormality. The rest of the cutaneous examination was normal and there were no other congenital anomalies. ACC is a rare, heterogeneous group of disorders characterized by the congenital absence of skin, which can be focal or widespread. It is thought to affect 1-3 per 10 000 live births. The exact cause of ACC is unclear. Various hypotheses have been suggested, including defective closure of the neural tube or embryonic fusion lines, intrauterine trauma, placental insufficiency, fetus papyraceus, amniotic membrane adhesions, intrauterine infections, teratogens and genetic mutations. The classification of ACC is based on the area affected, type of skin irregularity, associated congenital defects and mode of inheritance. Scalp ACC without multiple anomalies (category 1) is generally associated with an autosomal dominant or sporadic pattern of inheritance. These twins may have an autosomal dominant mutation that led to this phenotype. ACC can also be associated with fetus papyraceus or placental infarct. This is less likely in this case as only two embryos were transferred, and the pregnancy was dichorionic. Most cases of ACC associated with fetus papyraceus occur in monozygotic pregnancies. ACC lesions often heal spontaneously by re-epithelialization resulting in a hairless superficial scar. Twin one had a slightly smaller area affected by ACC and overlying eschar resolved several weeks after birth. Twin two has had no hair growth in the area. This case highlights the difficulties in ascertaining the aetiology of this rare condition in twin pregnancies.

Family History of Alport Syndrome with Spectrum of Chronic Kidney Disease, Dialysis and Transplantation

Introduction: Alport syndrome should be considered in the differential diagnosis of patients with persistent microhematuria. Electron microscopic examination of renal tissue remains the most widely available and applied means for diagnosing AS. The presence of diffuse thickening and multilamellation of the GBM predicts a progressive nephropathy, regardless of family history. Unfortunately, ultrastructural information alone does not establish the mode of transmission in a particular family. Method(s): 18 years-old male patient was followed in the clinic due to persistent microscopic haematuria and proteinuria. Family history is significant for one brother in his early 20s, who started to have the presentation early in life and his initial biopsy showed thin basement membrane disease. The brother subsequently progressed to renal failure and a repeat biopsy confirmed the presence of Alport syndrome. Another brother had end-stage renal disease and underwent renal transplantation. The patient status was revised, and genetic studies confirmed the presence of an autosomal recessive type of Alport syndrome involving collagen for A3 chain COL4A3. His kidney function remained stable initially with an estimated GFR of approximately 90 mL/min/1.73 m2. The most recent eGFR is around 70 ml/min/1.73 m2. His proteinuria disappeared once Losartan 25 mg was added to Ramipril 5 mg. His blood pressure has been on target. Creatinine increased to 147 micromol/L and he was diagnosed as having acute kidney injury on chronic renal disease which was obvious post covid infection, then back to baseline. Current proteinuria 3 g/g Cr on Angiotensin receptor blockers. BP 110/70, all other systemic examination is unremarkable. No hearing or visual abnormalities. Result(s): The initial renal manifestations in early childhood include asymptomatic-persistent microscopic hematuria and rarely gross hematuria. At the onset, the serum creatinine and blood pressure are normal. Over time, proteinuria, hypertension, and progressive renal insufficiency develop. ESRD usually occurs between the ages of 16 and 35 years and rarely can occur between 45 and 60 years. Renal biopsy findings of thinning and multilaminar splitting of the glomerular capillary basement membrane seen on electron microscopic examination are pathognomonic. In 2013, an expert panel issued guidelines recommending genetic testing as the gold standard for the diagnosis of Alport syndrome. Currently, a skin biopsy using commercially available monoclonal antibody against the type IV collagen alpha-5 chain (COL4A5). If the protein is clearly absent in a suspected male, a diagnosis of Alport syndrome can be made without further testing. Conclusion(s): Males with X-linked AS due to a deletion mutation of the alpha 5 chain of type IV collagen usually progress to ESRD by the second or third decade of life. Likewise, patients with autosomal recessive AS due to mutations affecting alpha 3 or 4 chains of type IV collagen tend to progress to ESRD by age 30. Autosomal-dominant AS with heterozygous mutations of COL4A3 or COL4A4 usually has a slower progression of CKD. Treatment is blood pressure control with RAAS inhibitors where clinically appropriate. Cyclosporine may be helpful in some patients with stage I and II CKD with significant proteinuria. Caution using calcineurin inhibitors is indicated in all patients with more advanced CKD stages due to potential nephrotoxicity. No conflict of interestCopyright © 2023

The inheritance of local wisdom for maintaining peace in multicultural society

PurposeThe research aims to investigate the value of local wisdom, analyse local wisdom for the harmony of a multicultural society and discover forms of inheritance of local wisdom for maintaining peace.Design/methodology/approachQualitative research was used in this research. The primary data were obtained through observation, in-depth interviews and focus group discussions. Secondary data were obtained through reports from agencies, such as Social Services and Central Bureau of Statistics, literature studies and news from the internet. The data validity technique used was source triangulation. The data were analysed with stages of data reduction, data presentation and conclusion.FindingsThe results showed that the local wisdom sedekah bumi, selamatan malam 1 suro, sadranan and kuda lumping contain values related to religion, cooperation, harmony, togetherness, kinship and cohesiveness;the implementation of local wisdom can strengthen social harmony;and the inheritance of local wisdom takes place sustainably from families and communities to the younger generation.Research limitations/implicationsThe research was conducted during the peak of COVID-19 cases in Central Java, Indonesia. Therefore, the data could not be obtained maximally.Practical implicationsThis research contributes widely not only to the village studied but also to other communities with similar conditions.Social implicationsThe inheritance of local wisdom can help maintain peace, unify societies and offer solution to social conflicts by implementing traditions containing humanity and peaceful values.Originality/valueThis research offers a new insight concerning the inheritance of local wisdom that can function as a tool to achieve a peaceful society and prevent social disasters from occurring.

Dental Implants And Orthodontics In Patients With Ectodermal Dysplasia: A Systemic Review

Ectodermal dysplasia is a hereditary disease that is associated with the involvement of organs with embryonic ectodermal structure such as teeth, nails, hair and sweat glands, lacrimal and salivary glands. The prevalence rate of this disease is 1 in every 100,000 people. The most common and severe form of ectodermal dysplasia is the X-linked hypo hidrotic type. The second common type of hidrotic ectodermal dysplasia is autosomal dominant, unlike the first type, sweat glands are not involved. Small and fragile nails, hyperkeratosis of the palms and feet, dry mouth, decreased tear production are some of the clinical symptoms of ectodermal dysplasia, which are the result of intolerance to heat. The facial features of the patient include a prominent forehead, sunken nose bridge, protruding ears, prominent lips, hypoplasia of the middle part of the face, and skin pigment around the eyes and mouth. Dental involvement is one of the most prominent features of ectodermal dysplasia, which can be seen in both primary and permanent tooth systems. Reduction in the number of teeth, delay in tooth growth, abnormal shape of anterior teeth in peg-shaped or conical form, smaller size of posterior teeth and enamel defects are observed. Alveolar ridge hypoplasia is also common due to the lack of teeth, followed by a decrease in the vertical height of the occlusion. A child with ectodermal dysplasia faces many problems in feeding, chewing, and speaking. Early treatment with dental prostheses can significantly reduce these problems.Copyright © 2023 Authors. All rights reserved.

Commentary on Act n. 14,010 of 2020, which established an emergency legal framework for relationships involving Private Law during the period of covid-19 pandemic

This paper analyses the set of rules established on Law n. 14,010 of 2020, as originated from Bill n. 1,179 of 2020, which determined the Emergency and Temporary Legal Framework for relationships involving Private Law during the period of Covid-19 pandemic in Brazil (Portuguese acronym: RJET). The aim of such Law was to regulate the most relevant themes regarding relationships involving Private law. In this sense, Law 14,010 of 2020 should be interpreted as an additional set of rules to those on the Brazilian Civil Code in order to deal with the legal issues arising from the Covid-19 pandemic, including those related to prescription and Inheritance Law. Based on legal scholarship and precedents, the paper intends to analyse the set of rules established on Law 14,010 of 2020 and its consequences. © 2021, Thomson Reuters Brasil Conteudo e Tecnologia. All rights reserved.

A CASE FOR THE AMENDMENT OF THE FORC ED ESTATE RULE IN BRAZILIAN INHERITANCE LAW

This study is based on the post-doctoral research carried out at the Department of Private Law (University of São Paulo Faculty of Law). After two and a half years of research, the work reflects the need for a possible amendment of the forced estate rule: the succession and inheritance quotas for necessary heirs. Before the post-doctoral internship there were compelling reasons for this possible amendment, but the Covid-19 pandemic seems to have brought forward considerable reasons for it to stay the same, exactly as it is regulated, which was noted during the research. The study takes into consideration the research conducted in the post-doctoral internship, exploring reasons for and against the continuity of the law, thoughts on the main challenges in contemporary Inheritance Law, using both the past and especially the present as parameters, as well as future challenges with respect to legal consequences of the pandemic's reality. © 2022, Thomson Reuters Brasil Conteudo e Tecnologia. All rights reserved.

Ethnocultural long-term care homes in Canada: a place for cultural inheritance and community building

This article discusses the overlooked role of recreation programmes in the ethnocultural and cultural-specific long-term care home from my standpoint as a recreation worker. First, the policy during the pandemic that prohibited visits by family members and volunteers revealed that they are important informal caregivers to fill in for the limitations of workers. Second, recreational programmes can also be considered as a practice of cultural inheritance: staff and volunteers learn their history and reconstruct them as collective memory. Third, the interaction between residents, volunteers, families and workers generates a sense of belonging to the ethnic community. Therefore, it can be considered a practice of community building for minority ethnic groups. By presenting the significant role of recreation workers in a long-term care home, I aim to question the meaning and value of care work in long-term care facilities.

Chemosensory Ability and Sensitivity in Health and Disease: Epigenetic Regulation and COVID-19.

Throughout the animal kingdom, our two chemical senses, olfaction and gustation, are defined by two primary factors: genomic architecture of the organisms and their living environment. During the past three years of the global COVID-19 pandemic, these two sensory modalities have drawn much attention at the basic science and clinical levels because of the strong association of olfactory and gustatory dysfunction with viral infection. Loss of our sense of smell alone, or together with a loss of taste, has emerged as a reliable indicator of COVID-19 infection. Previously, similar dysfunctions have been detected in a large cohort of patients with chronic conditions. The research focus remains on understanding the persistence of olfactory and gustatory disturbances in the post-infection phase, especially in cases with long-term effect of infection (long COVID). Also, both sensory modalities show consistent age-related decline in studies aimed to understand the pathology of neurodegenerative conditions. Some studies using classical model organisms show an impact on neural structure and behavior in offspring as an outcome of parental olfactory experience. The methylation status of specific odorant receptors, activated in parents, is passed on to the offspring. Furthermore, experimental evidence indicates an inverse correlation of gustatory and olfactory abilities with obesity. Such diverse lines of evidence emerging from basic and clinical research studies indicate a complex interplay of genetic factors, evolutionary forces, and epigenetic alterations. Environmental factors that regulate gustation and olfaction could induce epigenetic modulation. However, in turn, such modulation leads to variable effects depending on genetic makeup and physiological status. Therefore, a layered regulatory hierarchy remains active and is passed on to multiple generations. In the present review, we attempt to understand the experimental evidence that indicates variable regulatory mechanisms through multilayered and cross-reacting pathways. Our analytical approach will add to enhancement of prevailing therapeutic interventions and bring to the forefront the significance of chemosensory modalities for the evaluation and maintenance of long-term health.

Complete response to eculizumab in atypical hemolytic uremic syndrome with homozygous C3 mutation

Case Report: Atypical Hemolytic Uremic Syndrome (atypical HUS) is a rare and severe form of thrombotic microangiopathy (TMA) characterized by thrombocytopenia, intravascular hemolysis, and acute kidney injury with an incidence of 1 per million.1 Dysregulation and overactivation of the complement alternative pathway due to genetic mutations have been detected in 40-60% of patients with sporadic or familial atypical HUS.2,4 Triggers include viral illness, pregnancy, malignancy, sepsis, or sporadically with no known inciting event.1 Atypical HUS is a severe disease with a 2-10% risk of mortality, 33% risk of end-stage renal failure, and 50% chance of relapse.5 A 24-year-old female with prior history of atypical HUS at the age of 16 (with response to plasmapheresis) presented to the ER with a 5-day history of fever, chills, sore throat, nausea, vomiting, and dark urine. She tested positive for COVID-19. The exam revealed scleral icterus and scattered petechiae. Labs demonstrated nadir hemoglobin (Hgb) of 9.2 g/dL, platelet count of 52 000k/uL, haptoglobin < 30 mg/dL, peak LDH 1128U/L and creatinine 4.62 mg/dL. Urinalysis is consistent with hemoglobinuria. Schistocytes were noted on the peripheral smear. Rapid streptococcal antigen test and C3, C4, and IgA levels were unremarkable. Chest X-Ray, X-ray KUB, and ultrasound abdomen were unremarkable. The pregnancy test was negative. ADAMTS13 was >100%. Genetic analysis after the initial episode at age 16 revealed autosomal recessive inheritance c.193A > c gene mutations in C3. The patient received IV fluids, ceftriaxone for cystitis, and two units of Fresh Frozen Plasma. She initiated treatment with eculizumab. She also received the MENVEO and meningitis B vaccine per protocol due to the risk of meningitis from terminal complement deficiencies. After 4 infusions of eculizumab, patient's labs improved to platelet count of 307 000 k/uL, Hgb 12.2 g/ dL (nadir 9.2 g/dL), haptoglobin 78 mg/dL normalization of LDH and improved creatinine. Atypical HUS is a rare form of TMAwith mutations in C3 noted in 5% of cases. Complement cascade dysfunction leads to endothelial deposits and microvasculature damage. The resulting prothrombotic state causes obstructive microvascular thrombi predominantly affecting the kidneys but can cause multiorgan dysfunction. The SARS-CoV-2 virus may precipitate atypical HUS relapse due to endothelial damage and complement activation further intensified in patients with existing complement aberrations. Plasma exchange remains a standard of care for atypical HUS, as it effectively removes the antibodies and other proteins. Eculizumab a humanized monoclonal IgG antibody binds to complement proteins, preventing cleavage into C5a and C5b blocking C5b-9(MAC) activation. In patients with CFH, CFI, C3, and CFB mutations, eculizumab is the preferred intervention. Copyright © 2023 Southern Society for Clinical Investigation.

Analysis on the Relieving Effect of Local Cultural Spirit Inheritance on College Students' Anxiety

Background: On the one hand, with the development of the world's anti-globalization trend, the spread of the COVID-19 and the continuation of the Russian Ukrainian war, the psychological pressure on domestic college students' employment has increased, and some college students even suffer from anxiety. On the other hand, the rural revitalization strategy provides another way of thinking for the employment and anxiety relief from college students in China, that is, through the spiritual education of local culture, to change the employment outlook and world outlook of college students. Subjects and methods: To test the effectiveness and feasibility of local culture spirit inheritance education in alleviating college students' psychological anxiety by analyzing relevant literature and carrying out group teaching experiments, and to interview the selected research objects to understand the causes of their psychological anxiety and the impact of local culture spirit inheritance education. Result(s): Before and after the education experiment, the students in each group were tested by SAS (Self-rating Anxiety Scale). It was found that there was no significant difference in the SAS score data onto the students in each group before the experiment, but the SAS score of the group that received local culture education after the experiment was significantly lower than that of the control group that did not receive the intervention. Conclusion(s): The education of local culture and spirit inheritance to students can enable students to learn a lot of Chinese traditional cultural knowledge, so as to achieve the effect of self-cultivation and reduce students' psychological anxiety, especially the degree of employment anxiety. Copyright © Medicinska naklada - Zagreb, Croatia.

Increased Susceptibility and 9-Fold Increased Mortality From COVID- 19 in Patients With ADTKD-MUC1

Background: Patients with autosomal dominant tubulointerstitial kidney disease due to MUC1 mutations (ADTKD-MUC1) have a frameshift mutation on one allele of the MUC1 genotype, resulting in production an abnormal MUC1frameshift protein on on allele and normal MUC1 on the other allele. The C variant of the rs4072037 SNP increases production of MUC1 or MUC1fs if it is contained in the corresponding promoter. In addition to the kidneys, MUC1 is expressed in the nose and lungs. ADTKD-UMOD has a very similar clinical presentation, but UMOD is expressed only in the kidney. Method(s): We conducted a survey (after emergence of the delta variant) using the REDCAP database of 957 individuals in our ADTKD cohort to determine if COVID-19 infection was more severe in ADTKD-MUC1 patients. Result(s): There were 89 ADTKD-MUC1 and 132 ADTKD-UMOD respondents, with similar age, body mass index, transplant rates, vaccination rates,. 25/89(28%) ADTKDMUC1 individuals developed COVID-19 vs. 21/132(16%) ADTKD-UMOD individuals (odds ratio 2.35(1.6-3.1) (p=0.028). 10/41 (24%) ADTKD-MUC1 individuals died of COVID-19 vs. 1/30 (3%) ADTKD-UMOD individuals (p=0.013), with an odds ratio of 9.4 (7.2-11.5). The mean plasma mucin1 level in 13 infected and 23 uninfected ADTKDMUC1 individuals was 6.40+/-3.4 vs.10.89+/-3.82 U/mL (p=0.0012). Of ADTKD-MUC1 individuals who developed COVID-19, only 19% had the CC phenotype (associated with increased MUC1 production) vs. 51% of the ADTKD-MUC1 individuals who did not develop COVID-19 (p=0.01). There was no difference in rs4073037 genotype frequencies in the ADTKD-UMOD group. Of the 10 ADTKD-MUC1 patients who died, 8 were transplanted, with only 3 greater than 60 years of age. 50 percent had received 2 COVID-19 vaccines. Conclusion(s): Patients with ADTKD-MUC1 have a 2-fold increased odds of developing COVID-19 and a 9-fold increased mortality from COVID-19. Among ADTKD-MUC1 patients, those producing less MUC1 were more likely to develop COVID-19.

The Inheritance Rights of Infected Person with the Covid-19

Islamic law, as well as Indonesian law, prohibits the intentional killer’s entitlement to inheritance and bequest to him. This research aims to study the ruling on the felony of murder by transmitting Coronavirus (Covid-19) infection. Subsequently, the impact of inheritance and wills due to transmitting this infection deliberately or unintentionally. The research uses the descriptive approach and the analytical method in defining the felony of incapacitating murder and analyzing the impact of transmitting infection with this pandemic virus. The research comes with several results, including that whoever deliberately transmits infection with the Coronavirus (Covid-19) to people is regarded as the Spoilers on the land, that this felony deserves the punishment, that he is forbidden from inheriting if he is the heir, and that he is forbidden from the approval of the will if it is bequeathed to him. © 2022, JOURNAL OF INDONESIAN ISLAM. All rights reserved.

A New World - Changing the Landscape in End of Life Care, Hospice UK National Conference

The proceedings contain 245 papers. The topics discussed include: application of the lantern model to stories from the pandemic: its use in enhancing MDT working;hidden work and hidden workers in hospice care;carrying the torch for physician associates (PAS) working in UK hospices;'going against the grain of all we do': hospice staff experiences of moral distress during COVID-19;transformation of death and bereavement support processes across children and adult hospice services;development of a journal club to improve care in a hospice through evidence based practice;no barriers here! advance care planning and people with intellectual disabilities;online community of practice development - palliative care and homelessness;enhancing bereavement group support - changing from a social to a psycho-educational model;and hospice heritage stories: making every memory matter.

Impact of Genetic Testing in Nephrology: A Family's Experience with Dent Disease 2

Diagnosis of a genetic kidney disease can enhance treatment/management, allow patient/family counseling, and enable patient referral to specialists or clinical trials. Here we present a case study describing the use of a >380 gene panel associated with kidney diseases (The RenasightTM test, Natera, Inc.) to diagnose Dent disease 2 in a patient and their family members. A 41-year-old male was referred to Nephrology for evaluation of elevated SCr (4.6 mg/dL) and proteinuria. The patient’s medical history was unremarkable except for glaucoma in infancy. A renal biopsy identified glomerulomegaly. Genetic testing identified a likely pathogenic, hemizygous, frame-shift variant (c.311del;p.Cys104Phefs*2) in exon 5 of OCRL, an X-linked gene, which is associated with Dent disease 2. This genetic diagnosis prompted changes to the patient’s treatment plan, including patient counseling and preparation for renal replacement therapy (RRT). The patient’s 46-year-old brother was hospitalized due to COVID-19 symptoms with a SCr of 19.1 mg/dL. Due to limited medical history, it was unclear if he was presenting with acute kidney injury or chronic kidney disease. Although there was no evidence of nephrolithiasis or renal tubular acidosis typically associated with Dent disease 2, the family history prompted genetic testing that confirmed the presence of the familial variant in this patient. These genetic findings prevented delay in treatment, namely, initiation of RRT. Given the X-linked inheritance of Dent disease 2, the patients’ mother is an obligate carrier of the p.Cys104Phefs*2 variant in OCRL. Therefore, the third brother is an appropriate candidate for genetic testing due to his 50% chance of inheriting the familial variant. In this family, identification of an OCRL variant via broad panel renal genetic testing impacted patient counseling, management, and family testing. Notably, without genetic testing for the proband, his brother’s condition may have gone undiagnosed due to the atypical presentation, demonstrating the variability of OCRL-related conditions. Genetic testing can enable accurate disease diagnosis in individuals with an atypical presentation, syndromic kidney disease and/or a family history.