Association between COVID-19 severity and relatively high serum adiponectin levels at the time of admission.

At the beginning of 2020, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to epidemics worldwide. Obesity and visceral fat accumulation have been reported to be independent risk factors for severe COVID-19. Several reports have focused on the levels of adipocytokines/adipokines, including adiponectin (APN), which is exclusively secreted from adipocytes, although the importance of these factors in acute disease conditions remains unclear. Therefore, we investigated the relationship between serum adiponectin levels and COVID-19 severity. Patients with COVID-19 who were admitted to Sumitomo Hospital (Osaka, Japan) from May through October 2021 were included. A total of 107 patients were enrolled in this study. We obtained the anthropometric and clinical laboratory data of the patients at the time of admission and examined the associations between various parameters and COVID-19 severity. The mean period from onset to admission was 6.5 ± 2.8 days. We divided the patients into "non-severe" (mild, moderate-I and moderate-II) (n = 80) and "severe" (n = 27) groups. The "severe" patients were significantly older than "non-severe" patients. Additionally, no significant differences were observed in BMI, sex, or the period from onset to admission. The serum adiponectin levels of "severe" patients at the time of admission were significantly greater than those of "non-severe" patients even after adjusting for age, sex, and BMI. These results suggest that the serum APN levels at the time of admission can predict COVID-19 severity. However, further investigations on the changes in APN levels in acute diseases are needed.

Fatal case of Capnocytophaga sepsis from a dog bite in a patient with splenic hypoplasia.

Background: Capnocytophaga canimorsus is an oral commensal bacteria in dogs and may cause severe infection following a dog bite. This is a case of fatal C. canimorsus sepsis with acute infectious purpura fulminans (AIPF) in a healthy patient with splenic hypoplasia. Case Presentation: A healthy 49-year-old man was admitted to the intensive care unit (ICU) for septic shock and AIPF 4 days after a dog bite to his mouth. Computed tomography revealed a small spleen measuring 53 cm3 but no other source of infection. Despite intensive care, the patient died of multiple organ failure and progressive shock on the fifth ICU day. Polymerase chain reaction of blood samples identified the C. canimorsus gene on a later day. Conclusion: Capnocytophaga canimorsus from dog bites may cause fatal AIPF. Splenic hypoplasia and bite wounds in well-perfused areas such as the oral cavity are possible risk factors for sepsis. All dog bites should warrant medical attention.

Contact-free assessments of respiratory rate and volume with load cells under the bed legs in ventilated patients: a prospective exploratory observational study.

Development of reliable noncontact unrestrained respiratory monitoring is capable of augmenting the safety of hospitalized patients in the recovery phase. We previously discovered respiratory-related centroid shifts along the long axis of the bed with load cells under the bed legs [bed sensor system (BSS)]. This prospective exploratory observational study examined whether noncontact measurements of respiratory-related tidal centroid shift amplitude (TA-BSS; primary variable) and respiratory rate (RR-BSS; secondary variable) were correlated with tidal volume (TV-PN) and respiratory rate (RR-PN), respectively, measured by pneumotachograph in 14 ICU patients under mechanical ventilation. Among the 10-min average data automatically obtained for a 48-h period, 14 data samples were randomly selected from each patient. Successfully and evenly selected 196 data points for each variable were used for the purpose of this study. A good agreement between TA-BSS and TV-PN (Pearson's r = 0.669) and an excellent agreement between RR-BSS and RR-PN (r = 0.982) were observed. Estimated minute ventilatory volume [3.86 · TA-BSS · RR-BSS (MV-BSS)] was found to be in very good agreement with true minute volume (MV-PN) (r = 0.836). Although Bland-Altman analysis evidenced accuracy of MV-BSS by a small insignificant fixed bias (-0.02 L/min), a significant proportional bias of MV-BSS (r = -0.664) appeared to produce larger precision (1.9 L/min) of MV-BSS. We conclude that contact-free unconstrained respiratory monitoring with load cells under the bed legs may serve as a new clinical monitoring system, when improved.NEW & NOTEWORTHY We previously discovered that four load cells placed under the bed legs capture a centroid shift during respiration in bedridden human subjects. In 14 ICU patients under mechanical ventilation, this study evidenced that contact-free measurements of respiratory rate, tidal volume, and minute ventilation with the load cells correlated well with those measured by pneumotachograph. Possible clinical usefulness of this approach as a new clinical respiratory monitor is indicated.

Myocardial fat accumulation is associated with cardiac dysfunction in patients with type 2 diabetes, especially in elderly or female patients: a retrospective observational study.

BACKGROUND: Ectopic fat is fat that accumulates in or around specific organs or compartments of the body including myocardium. The clinical features of type 2 diabetes patients with high fat accumulation in the myocardium remain unknown. Moreover, little is known about the influence of myocardial fat accumulation in type 2 diabetes on coronary artery disease and cardiac dysfunction. We aimed to clarify the clinical features, including cardiac functions, of type 2 diabetes patients with myocardial fat accumulation. METHODS: We retrospectively enrolled type 2 diabetes patients who underwent ECG-gated coronary computed tomography angiography (CCTA) and abdominal computed tomography (CT) scan examinations within 1 year of CCTA from January 2000 to March 2021. High fat accumulation in the myocardium was defined as the low mean myocardial CT value of three regions of interest, and the associations between CT values and clinical characteristics or cardiac functions were assessed. RESULTS: In total, 124 patients were enrolled (72 males and 52 females). The mean age was 66.6 years, the mean BMI was 26.2 kg/m2, the mean ejection fraction (EF) was 67.6%, and the mean myocardial CT value was 47.7 Hounsfield unit. A significant positive correlation was found between myocardial CT value and EF (r = 0.3644, p = 0.0004). The multiple regression analyses also showed that myocardial CT value was independently associated with EF (estimate, 0.304; 95% confidence interval (CI) 0.092 to 0.517; p = 0.0056). Myocardial CT value showed significant negative correlations with BMI, visceral fat area and subcutaneous fat area (r = - 0.1923, - 0.2654, and -0.3569, respectively, p < 0.05). In patients who were ≥ 65 years or female, myocardial CT value showed significant positive correlations with not only EF (r = 0.3542 and 0.4085, respectively, p < 0.01) but also early lateral annular tissue Doppler velocity (Lat e') (r = 0.5148 and 0.5361, respectively, p < 0.05). The multiple regression analyses showed that myocardial CT value was independently associated with EF and Lat e' in these subgroups (p < 0.05). CONCLUSIONS: Patients with type 2 diabetes, especially in elderly or female patients, who had more myocardial fat had more severe left ventricular systolic and diastolic dysfunctions. Reducing myocardial fat accumulation may be a therapeutic target for type 2 diabetes patients.

Fluid restriction management in the treatment of COVID-19: a single-center observational study.

The relationship between fluid management and the severity of illness, duration of treatment, and outcome of coronavirus disease 2019 (COVID-19) is not fully understood. This study aimed to evaluate whether weight change during hospitalization was associated with COVID-19 severity, length of hospital stay, and route of admission. In this study, we assessed the effectiveness of fluid restriction management in patients with severe COVID-19. COVID-19 patients admitted to our hospital between July 2020 and October 2021 were analyzed. Patients were treated with standard drug therapy based on the Japanese guidelines and respiratory support according to the severity of the disease. Early enteral nutrition, defecation management, and anticoagulation therapy were also administered. Fluid restriction management was performed using furosemide and continuous renal replacement therapy as needed unless hemodynamic instability or hyperlactatemia was present. Patient background, route of admission (ambulance, A; transfer, T), weight at admission and discharge, the severity of illness (oxygen therapy, G1; mechanical ventilation, G2; extracorporeal membrane oxygenation, G3), in-hospital mortality, and length of hospital stay were analyzed. There were 116 subjects: G1 (n = 48), G2 (n = 43), and G3 (n = 25), with ages (median [IQR]) of 58 (47-70), 65 (53-71.5), 56 (51-62) years, 40 (83.3%), 31 (72.1%), and 19 (76.0%) males, respectively. Hospital stays were 4.5 (2-7), 10 (7-16), and 18 (15-26) days, and the in-hospital mortality rates were 0 (0%), 7 (16.3%), and 8 (32%), respectively. Body mass index on admission was 26 (23.1-30.2), 27.1 (22.7-31.1), and 31.5 (27.1-33.1) kg/m2, and weight loss during admission was 1.1 (0-2.9), 4.6 (2.3-5.7), 9.2 (5.6-10.5) kg (P < 0.001, Jonckheere-Terpstra test. Weight loss in the severe group (G2 + G3) was 3.4 (0.5-5.8) kg [A, n = 12] and 5.6 (4.4-9) kg [T, n = 43] [P = 0.026, Mann-Whitney U test]. The lengths of hospital stay were 5 (2-7), 9 (7-15), and 18 (12-26) days [P < 0.001, Jonckheere-Terpstra test]. In our fluid restriction management, patients with severe COVID-19 had significant longer hospital length of stay, weight loss, especially those who were transferred to the hospital.

Increase in glycemic set point, alongside a decrease in waist circumference, in the non-diabetic population during the Japanese National Intervention Program for metabolic syndrome: A single-center, large-scale, matched-pair analysis.

BACKGROUND: In 2008, the Japanese government implemented a National Intervention Program for metabolic syndrome. Low-risk individuals were not direct targets of this intervention. Nevertheless, they were indirectly enlightened by this massive campaign. Documentation of the metabolic shifts in low-risk individuals following the program launch may inform public health policy regarding approaches to metabolic risks in the general population. METHODS: We conducted a cross-sectional analysis of data from non-diabetic participants who underwent general health check-ups at the Physical Check-up Center of Sumitomo Hospital. Participants during 2007-2008 were pair-matched with those during 2015-2016 with respect to sex, age, smoking status, hemoglobin level, and red blood cell (RBC) count. Each participant was included only once in the study. RESULTS: Totals of 3,140 men and 2,048 women were pair-matched. The non-diabetic participants showed lower waist circumference, blood pressure, heart rate, and serum lipid concentrations during the second study period. In contrast, the entire distributions of fasting plasma glucose (FPG) concentration in both sexes and glycated hemoglobin (HbA1c) in women were shifted upwards. In men, Δ FPG was +1.6 mg/dL (P < 0.001) and Δ HbA1c was ±0% (P = 0.6). In women, Δ FPG was +3.0 mg/dL (P < 0.001), and Δ HbA1c was +0.1% (P < 0.001). Δ Homeostasis model assessment of ß-cell function was -6.6 in men (P < 0.001) and -10.3 in women (P < 0.001). The homeostasis model assessment of insulin resistance did not change significantly. CONCLUSIONS: The "glycemic set point" has increased in non-diabetic people in Japan during recent years. Lifestyle or environmental changes may have caused this metabolic shift through obesity-independent pathways, possibly through effects on pancreatic ß-cell function. The underlying mechanism awaits further investigation.

Resuscitation from Cardiac Arrest with Tension Gastrothorax Due to Acquired Diaphragmatic Hernia.

Tension gastrothorax is a rare cause of obstructive shock induced by a distended stomach herniating into the thorax through a diaphragmatic defect. We report the process of diagnosis and emergency treatment for tension gastrothorax during cardiopulmonary resuscitation (CPR). A 71-year-old woman with multiple surgical histories had nausea and vomiting for two days. She was transferred to our hospital with circulatory failure and loss of consciousness. She presented pulseless electric activity and received CPR immediately after arrival. The right atrium and right ventricle were collapsed in the echocardiography. A chest X-ray demonstrated a dilated intestine extending from the peritoneal cavity to the mediastinum. The nasogastric tube (NGT) drained 1000 mL of stomach content and alleviated the abdominal distension, and spontaneous circulation returned immediately after the drainage. Thoracoabdominal CT showed the stomach and the transverse colon had escaped from the peritoneal cavity to the mediastinum. We diagnosed the situation as tension gastrothorax due to an acquired diaphragmatic hernia. History of multiple surgery and multiple operative scars was the first step of the diagnostic process, and the chest X-ray during CPR was the key to the diagnosis. Tension gastrothorax can be misdiagnosed as other conditions. A chest X-ray should be preceded in non-trauma settings, unlike the setting of a tension pneumothorax in trauma patients. Gastrointestinal decompression with NGT placement could be attempted quickly to improve the hemodynamic condition.

Successful application of angioembolization and thoracic endovascular aortic repair (TEVAR) in a retrograde type-A acute aortic dissection with polytrauma.

A 53-year-old man underwent thoracic endovascular aortic repair for persistent false lumen perfusion and limb salvage because of type A aortic dissection, severe lower-limb ischemia, and bleeding (mediastinal hematoma, bilateral lung contusion, liver injury, and splenic injury) caused by blunt trauma. We embolized the left supreme intercostal artery to control active mediastinal hemorrhage. Acute hemorrhage and leg ischemia were well controlled; however, residual blood flow in the false lumen persisted. We performed a Zone 2 thoracic endovascular aortic repair and discharged the patient on day 67. Thoracic endovascular aortic repair is a practical option for treating traumatic type A dissection.

Development and Evaluation of HILIC-type Sorbents Modified with Hydrophilic Copolymers for Solid-phase Extraction.

Hydrophilic interaction chromatography (HILIC) has attractive attention for the separation of water-soluble compounds via HPLC. There are, however, few studies on the pretreatment of the HILIC-type solid-phase extraction (SPE) due to the difficulty of obtaining the HILIC-type sorbent. Therefore, the development of HILIC-type sorbents for SPE is essential. In this study, four different hydrophilic copolymers, namely diallylamine-maleic acid copolymer (DAM), diallylamine-acrylamide copolymer (DAA), allylamine-maleic acid copolymer (MAM), and partly methylcarbonylated allylamine acetate copolymer (MAC), were immobilized on glycidyl methacrylate (GMA)-base resin, and their adsorptive properties were evaluated. The results of the physical and adsorptive properties indicated that a balance between the water content of the water-enriched layer on sorbent and the amount of hydrophilic copolymer immobilized on the GMA-base resin was vital for the adsorption in HILIC-type sorbent for SPE.

The use of veno-venous extracorporeal membrane oxygenation for massive hemoptysis following a traumatic lung injury: a case report.

BACKGROUND: Published reports regarding the use of veno-venous extracorporeal membrane oxygenation (V-V ECMO) for massive hemoptysis following a thoracic injury are still scarce. CASE PRESENTATION: A 34-year-old man developed massive hemoptysis from the right lung after a 2 m fall and being compressed with an iron pipe weighing 500 kg. He was immediately intubated using a double-lumen tube, and one-lung ventilation was started. Endotracheal hemorrhage was controlled by sealing the right lumen. V-V ECMO was initiated to endure the lethal hypoxemia while waiting for the right lung to heal. He came off of V-V ECMO after 17 days and was discharged on foot on day 46. CONCLUSION: The strategy of using V-V ECMO in combination with one-lung ventilation is useful and should be strongly considered to save lethal massive hemoptysis cases following traumatic lung injury.

Penetrating Anorectal Injury Caused by a Wild Boar Attack: A Case Report.

Wild boar attacks have rarely been reported in the medical literature. This is the case of an 83-year-old male farmer who was assaulted from behind by an injured adult wild boar. He presented with hemorrhagic shock after sustaining injuries to the right profunda femoris artery and right sciatic nerve as well as significant soft-tissue injuries, bilateral iliac wing fractures, an open pneumothorax, and an anorectal injury. The anorectal injury was treated with fecal diversion but was complicated by soft-tissue infection in the surrounding dead space. The patient needed multiple operations, including removal of the distal rectum and creation of a permanent colostomy. In this report, we highlighted the characteristics of anorectal trauma caused by a wild boar attack. We conclude that penetrating anorectal injuries caused by this type of attack can be associated with extensive soft-tissue damage despite externally appearing to be simple puncture wounds. Anorectal combat injuries have demonstrated similar extensive surrounding soft-tissue injuries and propensity for infection; therefore, this case supports adopting a similar treatment strategy, that of serial and radical debridement, to treat certain wild boar injuries.

Enzymatic properties and the gene structure of a cold-adapted laminarinase from Pseudoalteromonas species LA.

We isolated a laminarin-degrading cold-adapted bacterium strain LA from coastal seawater in Sagami Bay, Japan and identified it as a Pseudoalteromonas species. We named the extracellular laminarinase LA-Lam, and purified and characterized it. LA-Lam showed high degradation activity for Laminaria digitata laminarin in the ranges of 15-50°C and pH 5.0-9.0. The major terminal products degraded from L. digitata laminarin with LA-Lam were glucose, laminaribiose, and laminaritriose. The degradation profile of laminarioligosaccharides with LA-Lam suggested that the enzyme has a high substrate binding ability toward tetrameric or larger saccharides. Our results of the gene sequence and the SDS-PAGE analyses revealed that the major part of mature LA-Lam is a catalytic domain that belongs to the GH16 family, although its precursor is composed of a signal peptide, the catalytic domain, and three-repeated unknown regions.

Association between off-hour presentation and endotracheal-intubation-related adverse events in trauma patients with a predicted difficult airway: A historical cohort study at a community emergency department in Japan.

BACKGROUND: A reduction in medical staff such as occurs in hospitals during nights and weekends (off hours) is associated with a worse outcome in patients with several unanticipated critical conditions. Although difficult airway management (DAM) requires the simultaneous assistance of several appropriately trained medical caregivers, data are scarce regarding the association between off-hour presentation and endotracheal intubation (ETI)-related adverse events, especially in the trauma population. The aim of this study was to determine whether off-hour presentation was associated with ETI complications in injured patients with a predicted difficult airway. METHODS: This historical cohort study was conducted at a Japanese community emergency department (ED). All patients with inhalation burn, comminuted facial trauma (Abbreviated Injury Scale Score Face ≥3), and penetrating neck injury who underwent ETI from January 2007 to January 2016 in our ED were included. Primary exposure was off-hour presentation, defined as the period from 6:01 PM to 8:00 AM weekdays plus the entire weekend. The primary outcome measure was the occurrence of an ETI-related adverse event, including hypoxemia, unrecognized esophageal intubation, regurgitation, cardiac arrest, ETI failure rescued by emergency surgical airway, cuff leak, and mainstem bronchus intubation. RESULTS: Of the 123 patients, 75 (61.0 %) were intubated during off hours. Crude analysis showed that off-hour presentation was significantly associated with an increased risk of ETI-related adverse events [odds ratio (OR), 2.5; 95 % confidence interval (CI), 1.1-5.6; p = 0.033]. The increased risk remained significant after adjusting for potential confounders, including operator being an anesthesiologist, use of a paralytic agent, and injury severity score (OR, 3.0; 95 % CI, 1.1-8.4; p = 0.034). CONCLUSIONS: In this study, off-hour presentation was independently associated with ETI-related adverse events in trauma patients with a predicted difficult airway. These data imply the need for more attentive hospital care during nights and weekends.

Synthesis of a Conjugated D-A Polymer with Bi(disilanobithiophene) as a New Donor Component.

A new conjugated donor-acceptor (D-A) polymer pDSBT2-BT containing bi(disilano-bisthiophene) and benzothiadiazole as donor and acceptor units, respectively, was prepared. The polymer showed a broad UV-vis absorption band at λmax = 599 nm in chlorobenzene. The absorption band was shifted to λmax = 629 nm when the polymer was measured as a film, indicating enhanced interchain interactions of the polymer. Bulk hetero-junction polymer solar cells (BHJ-PSCs) were fabricated using pDSBT2-BT and PC71BM as host and guest materials, respectively. Optimization of cell fabrication conditions provided a maximal power conversion efficiency of 3.3% and the following cell parameters: Voc = 0.86 V, Jsc = 7.56 mA/cm², and FF = 0.51. Although the efficiency still leaves much to be desired, these data underscore the potential of pDSBT2-BT as a high-voltage polymer solar cell material.

Carlactone-type strigolactones and their synthetic analogues as inducers of hyphal branching in arbuscular mycorrhizal fungi.

Hyphal branching in the vicinity of host roots is a host recognition response of arbuscular mycorrhizal fungi. This morphological event is elicited by strigolactones. Strigolactones are carotenoid-derived terpenoids that are synthesized from carlactone and its oxidized derivatives. To test the possibility that carlactone and its oxidized derivatives might act as host-derived precolonization signals in arbuscular mycorrhizal symbiosis, carlactone, carlactonoic acid, and methyl carlactonoate as well as monohydroxycarlactones, 4-, 18-, and 19-hydroxycarlactones, were synthesized chemically and evaluated for hyphal branching-inducing activity in germinating spores of the arbuscular mycorrhizal fungus Gigaspora margarita. Hyphal branching activity was found to correlate with the degree of oxidation at C-19 methyl. Carlactone was only weakly active (100 ng/disc), whereas carlactonoic acid showed comparable activity to the natural canonical strigolactones such as strigol and sorgomol (100 pg/disc). Hydroxylation at either C-4 or C-18 did not significantly affect the activity. A series of carlactone analogues, named AD ester and AA'D diester, was synthesized by reacting formyl Meldrum's acid with benzyl, cyclohexylmethyl, and cyclogeranyl alcohols (the A-ring part), followed by coupling of the potassium enolates of the resulting formylacetic esters with the D-ring butenolide. AD ester analogues exhibited moderate activity (1 ng-100 pg/disc), while AA'D diester analogues having cyclohexylmethyl and cyclogeranyl groups were highly active on the AM fungus (10 pg/disc). These results indicate that the oxidation of methyl to carboxyl at C-19 in carlactone is a prerequisite but BC-ring formation is not essential to show hyphal branching activity comparable to that of canonical strigolactones.

Dissecting Human Gene Functions Regulating Islet Development With Targeted Gene Transduction.

During pancreas development, endocrine precursors and their progeny differentiate, migrate, and cluster to form nascent islets. The transcription factor Neurogenin 3 (Neurog3) is required for islet development in mice, but its role in these dynamic morphogenetic steps has been inferred from fixed tissues. Moreover, little is known about the molecular genetic functions of NEUROG3 in human islet development. We developed methods for gene transduction by viral microinjection in the epithelium of cultured Neurog3-null mutant fetal pancreas, permitting genetic complementation in a developmentally relevant context. In addition, we developed methods for quantitative assessment of live-cell phenotypes in single developing islet cells. Delivery of wild-type NEUROG3 rescued islet differentiation, morphogenesis, and live cell deformation, whereas the patient-derived NEUROG3(R107S) allele partially restored indicators of islet development. NEUROG3(P39X), a previously unreported patient allele, failed to restore islet differentiation or morphogenesis and was indistinguishable from negative controls, suggesting that it is a null mutation. Our systems also permitted genetic suppression analysis and revealed that targets of NEUROG3, including NEUROD1 and RFX6, can partially restore islet development in Neurog3-null mutant mouse pancreata. Thus, advances described here permitted unprecedented assessment of gene functions in regulating crucial dynamic aspects of islet development in the fetal pancreas.

An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.

The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus.

Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells.

Pancreatic islet ß-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional ß-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native ß-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark ß-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.001.

Reconstituting pancreas development from purified progenitor cells reveals genes essential for islet differentiation.

Developmental biology is challenged to reveal the function of numerous candidate genes implicated by recent genome-scale studies as regulators of organ development and diseases. Recapitulating organogenesis from purified progenitor cells that can be genetically manipulated would provide powerful opportunities to dissect such gene functions. Here we describe systems for reconstructing pancreas development, including islet ß-cell and α-cell differentiation, from single fetal progenitor cells. A strict requirement for native genetic regulators of in vivo pancreas development, such as Ngn3, Arx, and Pax4, revealed the authenticity of differentiation programs in vitro. Efficient genetic screens permitted by this system revealed that Prdm16 is required for pancreatic islet development in vivo. Discovering the function of genes regulating pancreas development with our system should enrich strategies for regenerating islets for treating diabetes mellitus.