Tissue homeostasis is perturbed in a diversity of inflammatory pathologies. These changes can elicit endoplasmic reticulum (ER) stress, protein misfolding, and cell death. ER stress triggers the unfolded protein response (UPR), which can promote recovery of ER proteostasis and cell survival or trigger programmed cell death. Here, we leveraged single-cell RNA sequencing to define dynamic transcriptional states associated with the adaptive versus terminal UPR in the mouse intestinal epithelium. We integrated these transcriptional programs with genome-scale CRISPR screening to dissect the UPR pathway functionally. We identified QRICH1 as a key effector of the PERK-eIF2α axis of the UPR. QRICH1 controlled a transcriptional program associated with translation and secretory networks that were specifically up-regulated in inflammatory pathologies. Thus, QRICH1 dictates cell fate in response to pathological ER stress.The circadian clock coordinates daily rhythmicity of biochemical, physiologic, and behavioral functions in humans. Gene expression, cell division, and DNA repair are modulated by the clock, which gives rise to the hypothesis that clock dysfunction may predispose individuals to cancer. Although the results of many epidemiologic and animal studies are consistent with there being a role for the clock in the genesis and progression of tumors, available data are insufficient to conclude that clock disruption is generally carcinogenic.  https://www.selleckchem.com/products/mizagliflozin.html  Similarly, studies have suggested a circadian time-dependent efficacy of chemotherapy, but clinical trials of chronochemotherapy have not demonstrated improved outcomes compared with conventional regimens. Future hypothesis-driven and discovery-oriented research should focus on specific interactions between clock components and carcinogenic mechanisms to realize the full clinical potential of the relationship between clocks and cancer.A 41-year-old woman was diagnosed with pre-eclampsia at 35 weeks gestation. She was treated with antihypertensives but, unfortunately, her condition became complicated by severe hyponatraemia. Her sodium levels rapidly dropped to 125 mmol/L. The cause for the hyponatraemia was the syndrome of inappropriate antidiuretic hormone secretion. She was initially managed with fluid restriction, but an emergency caesarean section was necessary in view of fetal distress. Her sodium levels returned to normal within 48 hours of delivery.Pre-eclampsia is rarely associated with hyponatraemia. A low maternal sodium level further increases the mother's risk for seizures during this state. Additionally, the fetal sodium rapidly equilibrates to the mother's and may result in fetal tachycardia, jaundice and polyhdraminios. All these factors may necessitate an emergency fetal delivery.Nocardiosis is a rare infection in patients with myasthenia gravis (MG). We identified three cases of MG admitted with nocardiosis in our unit. We performed systematic literature search of previous publications and identified 18 patients. This paper presents three patients and reviews the clinical characteristics of 21 patients. The first case was a 69-year-old woman with thymomatous MG who presented with pustules and left lower limb pain. Evaluation showed osteomyelitis of the pubic ramus and ileopsoas abscess. The second case was a 54-year-old man who presented in myasthenic crisis due to pulmonary nocardiosis. The third case was a 48-year-old man with thymomatous MG who presented with lung abscess. All of them recovered completely after treatment with co-trimoxazole. Analysis of the 21 patients identified four risk factors for nocardiosis in MG elderly men; thymoma; immunosuppressant medication, mainly steroid therapy; and pre-existing lung disease. Lungs was the most common site of infection. Suppurative disease was common manifestation regardless of organ involved. Clinical course is not unfavourable.Hafnia alvei is a rare, poorly understood commensal bacterium which has, on occasion, been shown to infect humans. We present two cases. The first patient presented with a 1-week history of dyspnoea, pleurisy and a productive cough, and the second with a prodrome of fatigue and night sweats. The former had a history of severe chronic obstructive pulmonary disease and the latter had a history of Crohn's disease. Both patients had underlying comorbidities and immunosuppression, but differed in presentation, radiological findings and recovery. This case series aims to remind readers of the broad differential of pathogens that can lead to disease in the immunocompromised and that one should not dismiss atypical cultured bacteria as commensal too hastily.Haemophagocytic lymphohistiocytosis (HLH) is an aggressive syndrome which has characteristic symptoms and laboratory findings. Infection is a common trigger of HLH. We report a 2700 g male infant with persistent fever, massive hepatosplenomegaly and severe thrombocytopaenia. Laboratory evidence of primary dengue infection was detected. Investigations revealed hypertriglyceridaemia, hypofibrinogenaemia, hyperferritinaemia and elevated soluble CD25. Bone marrow examination revealed haemophagocytes. The diagnostic criteria for HLH were fulfilled. A diagnosis of secondary HLH triggered by primary dengue infection was considered. Dexamethasone was initiated and continued for 8 weeks. He responded clinically with regression of hepatosplenomegaly, was afebrile and platelet counts normalised. Dengue-associated HLH is often missed clinically as treating physicians focus more on the underlying infection and its treatment. In neonates, HLH should be considered as differential diagnosis of sepsis and other viral infections, particularly in situations of inappropriate response to standard management.Cardiac tamponade as the initial presentation of hypothyroidism is extremely rare. We report the case of a 48-year-old man admitted for acute respiratory distress, with cardiac ultrasound showing compressive pericardial effusion. Percutaneous pericardiocentesis was performed leading to a rapid clinical improvement. Laboratory tests confirmed severe hypothyroidism related to Hashimoto's disease. Despite hormone replacement therapy, pericardial effusion recurred after 3 weeks, requiring surgical drainage. Pericardial histology highlighted slight chronic fibrous pericarditis. The cardiac ultrasound scan performed 4 months later showed a well-tolerated chronic pericardial effusion. In conclusion, hypothyroidism should be suspected in case of cardiac tamponade especially in the absence of tachycardia, or in winter when myxoedema is prone to decompensation. Prognosis is generally good under hormone replacement therapy but ultrasound monitoring should be carried out at least until euthyroidism is achieved.