Disorder and demixing in bidisperse particle systems assembling bcc crystals.

Colloidal and nanoparticle self-assembly enables the creation of ordered structures with a variety of electronic and photonic functionalities. The outcomes of the self-assembly processes used to synthesize such structures, however, strongly depend on the uniformity of the individual nanoparticles. Here, we explore the simplest form of particle size dispersity-bidispersity-and its impact on the self-assembly process. We investigate the robustness of self-assembling bcc-type crystals via isotropic interaction potentials in binary systems with increasingly disparate particle sizes by determining their terminal size ratio-the most extreme size ratio at which a mixed binary bcc crystal forms. Our findings show that two-well pair potentials produce bcc crystals that are more robust with respect to particle size ratio than one-well pair potentials. This suggests that an improved self-assembly process is accomplished with a second attractive length scale encoded in the particle-particle interaction, which stabilizes the second-nearest neighbor shell. In addition, we document qualitative differences in the process of ordering and disordering: in bidisperse systems of particles interacting via one-well potentials, we observe a breakdown of order prior to demixing, while in systems interacting via two-well potentials, demixing occurs first and bcc continues to form in parts of the droplet down to low size ratios.

Predictors of Intrahospital Mortality in Aneurysmal Subarachnoid Hemorrhage after Endovascular Embolization.

Background and Objectives: Aneurysmal subarachnoid hemorrhage (ASAH) is defined as bleeding in the subarachnoid space caused by the rupture of a cerebral aneurysm. About 11% of people who develop ASAH die before receiving medical treatment, and 40% of patients die within four weeks of being admitted to hospital. There are limited data on single-center experiences analyzing intrahospital mortality in ASAH patients treated with an endovascular approach. Given that, we wanted to share our experience and explore the risk factors that influence intrahospital mortality in patients with ruptured intracranial aneurysms treated with endovascular coil embolization. Materials and Methods: Our study was designed as a clinical, observational, retrospective cross-sectional study. It was performed at the Department for Radiology, University Clinical Center Kragujevac in Kragujevac, Serbia. The study inclusion criteria were ≥18 years, admitted within 24 h of symptoms onset, acute SAH diagnosed on CT, aneurysm on DSA, and treated by endovascular coil embolization from January 2014 to December 2018 at our institution. Results: A total of 66 patients were included in the study-48 (72.7%) women and 18 (27.3%) men, and 19.7% of the patients died during hospitalization. After adjustment, the following factors were associated with in-hospital mortality: a delayed ischemic neurological deficit, the presence of blood in the fourth cerebral ventricle, and an elevated urea value after endovascular intervention, increasing the chances of mortality by 16.3, 12, and 12.6 times. Conclusions: Delayed cerebral ischemia and intraventricular hemorrhage on initial head CT scan are strong predictors of intrahospital mortality in ASAH patients. Also, it is important to monitor kidney function and urea levels in ASAH patients, considering that elevated urea values after endovascular aneurysm embolization have been shown to be a significant risk factor for intrahospital mortality.

Neuroimaging Modalities Used for Ischemic Stroke Diagnosis and Monitoring.

Strokes are one of the global leading causes of physical or mental impairment and fatality, classified into hemorrhagic and ischemic strokes. Ischemic strokes happen when a thrombus blocks or plugs an artery and interrupts or reduces blood supply to the brain tissue. Deciding on the imaging modality which will be used for stroke detection depends on the expertise and availability of staff and the infrastructure of hospitals. Magnetic resonance imaging provides valuable information, and its sensitivity for smaller infarcts is greater, while computed tomography is more extensively used, since it can promptly exclude acute cerebral hemorrhages and is more favorable speed-wise. The aim of this article was to give information about the neuroimaging modalities used for the diagnosis and monitoring of ischemic strokes. We reviewed the available literature and presented the use of computed tomography, CT angiography, CT perfusion, magnetic resonance imaging, MR angiography and MR perfusion for the detection of ischemic strokes and their monitoring in different phases of stroke development.

Development of an automated platform for the optimal production of glycoconjugate vaccines expressed in Escherichia coli.

Protein Glycan Coupling Technology (PGCT) uses purposely modified bacterial cells to produce recombinant glycoconjugate vaccines. This vaccine platform holds great potential in this context, namely due to its modular nature, the simplified production process in comparison to traditional chemical conjugation methods, and its amenability to scaled-up operations. As a result, a considerable reduction in production time and cost is expected, making PGCT-made vaccines a suitable vaccine technology for low-middle income countries, where vaccine coverage remains predominantly low and inconsistent. This work aims to develop an integrated whole-process automated platform for the screening of PGCT-made glycoconjugate vaccine candidates. The successful translation of a bench scale process for glycoconjugate production to a microscale automated setting was achieved. This was integrated with a numerical computational software that allowed hands-free operation and a platform adaptable to biological variation over the course of a production process. Platform robustness was proven with both technical and biological replicates and subsequently the platform was used to screen for the most favourable conditions for production of a pneumococcal serotype 4 vaccine candidate. This work establishes an effective automated platform that enabled the identification of the most suitable E. coli strain and genetic constructs to be used in ongoing early phase research and be further brought into preclinical trials.

Why DNA Is a More Effective Scaffold than RNA in Nucleic Acid-Based Asymmetric Catalysis-Supramolecular Control of Cooperative Effects.

Nucleic acids can form efficient hybrid catalysts for asymmetric catalysis upon binding of low-molecular-weight metal complexes. Up to now DNA has been the preferred nucleic acid component, while RNA was largely ignored. It is shown that despite RNA's successful use in ribozymes, RNA is less suited for use in hybrid catalysts for asymmetric catalysis. A common dimethyl bipyridine copper complex does not form highly active and enantioselective hybrid catalysts with RNA due to the absence of synergistic effects between the copper complex and dsRNA.

Enantioselective Catalysis by Using Short, Structurally Defined DNA Hairpins as Scaffold for Hybrid Catalysts.

A new type of DNA metal complex hybrid catalyst, which is based on single-stranded DNA oligonucleotides, is described. It was shown that oligonucleotides as short as 14 nucleotides that fold into hairpin structures are suitable as nucleic acid components for DNA hybrid catalysts. With these catalysts, excellent enantioinduction in asymmetric Diels-Alder reactions with selectivity values as high as 96 % enantiomeric excess (ee) can be achieved. Molecular dynamics simulations indicate that a rather flexible loop combined with a rigid stem region provides DNA scaffolds with these high selectivity values.

The Distribution of Dermatologists in the Philippines.

BACKGROUND: Equitable health manpower distribution is essential for the successful implementation of the Universal Health Care (UHC) program by the Philippine Department of Health. Mapping the distribution and profile of dermatologists in the Philippines can improve Filipinos' access to skin disease treatment. METHODS: A review of the database of dermatologists from the Philippine Dermatological Society (PDS) members' directory (as of November 2023), as well as the Philippine Health Insurance Corporation (PhilHealth) database (as of July 2023), was conducted. The distribution of PDS-accredited dermatologists was analyzed by geographic location, demographic profile (age and sex), density (per 100,000 people), and the dermatologist-to-general practitioner (GP) ratio. Heatmaps illustrating the distribution of dermatologists in the Philippines and the ratio of PhilHealth-accredited PDS board-certified dermatologists to GPs were created. RESULTS: Out of 1389 PDS board-certified dermatologists, 1345 resided in the Philippines. The majority were women (1221/1345, 90.78%), with a median age of 47 years (range: 23 to 85). More than half were practicing in the National Capital Region (NCR) (684/1345, 50.86%). The overall dermatologist density was approximately 1 per 100,000 people (1.19); it was highest for the Luzon Island group (1.54) (NCR, 4.80) and lowest for the Mindanao Island group (0.27; the Bangsamoro Autonomous Region of Muslim Mindanao or BARMM, 0.04). Less than one-third (396/1345, 29.44%) of dermatologists were PhilHealth-accredited, with a density of 0.35 dermatologists per 100,000 people. Out of 45218 PhilHealth-accredited physicians, 396 (0.88%) were dermatologists while 11748 (25.98%) were GPs. The overall dermatologist-to-GP ratio among PhilHealth-accredited physicians was 1:30; it was highest in the Luzon Island group (1:20) and lowest in the Mindanao Island group (1:118). CONCLUSION: The Philippines lacks dermatologists in regions outside the NCR. The majority are women, and few are PhilHealth-accredited. The dermatologist-to-GP ratio among PhilHealth-accredited physicians is low. Dermatology training programs should encourage more applicants, especially men, and prioritize applicants from underserved regions.

Congenital hyperinsulinism and novel KDM6A duplications -resolving pathogenicity with genome and epigenetic analyses.

CONTEXT: Hyperinsulinemic hypoglycemia (HI) can be the presenting feature of Kabuki syndrome (KS), which is caused by loss-of-function variants in KMT2D or KDM6A. As these genes play a critical role in maintaining methylation status in chromatin, individuals with pathogenic variants have a disease-specific epigenomic profile -an episignature. OBJECTIVE: We evaluated the pathogenicity of three novel partial KDM6A duplications identified in three individuals presenting with neonatal-onset HI without typical features of KS at the time of genetic testing. METHODS: Three different partial KDM6A duplications were identified by routine targeted next generation sequencing for HI and initially classified as variants of uncertain significance (VUS) as their location, and hence their impact on the gene, was not known. Whole genome sequencing (WGS) was undertaken to map the breakpoints of the duplications with DNA methylation profiling performed in two individuals to investigate the presence of a KS-specific episignature. RESULTS: WGS confirmed the duplication in proband 1 as pathogenic as it caused a frameshift in the normal copy of the gene leading to a premature termination codon. The duplications identified in probands 2 and 3 did not alter the reading frame and therefore their significance remained uncertain after WGS. Subsequent DNA methylation profiling identified a KS-specific episignature in proband 2 but not in proband 3. CONCLUSIONS: Our findings confirm a role for KDM6A partial gene duplications in the etiology of KS and highlight the importance of performing in-depth molecular genetic analysis to properly assess the clinical significance of VUS's in the KDM6A gene.

Chromosome 20p11.2 deletions cause congenital hyperinsulinism via the loss of FOXA2 or its regulatory elements.

Persistent congenital hyperinsulinism (HI) is a rare genetically heterogeneous condition characterised by dysregulated insulin secretion leading to life-threatening hypoglycaemia. For up to 50% of affected individuals screening of the known HI genes does not identify a disease-causing variant. Large deletions have previously been used to identify novel regulatory regions causing HI. Here, we used genome sequencing to search for novel large (>1 Mb) deletions in 180 probands with HI of unknown cause and replicated our findings in a large cohort of 883 genetically unsolved individuals with HI using off-target copy number variant calling from targeted gene panels. We identified overlapping heterozygous deletions in five individuals (range 3-8 Mb) spanning chromosome 20p11.2. The pancreatic beta-cell transcription factor gene, FOXA2, a known cause of HI was deleted in two of the five individuals. In the remaining three, we found a minimal deleted region of 2.4 Mb adjacent to FOXA2 that encompasses multiple non-coding regulatory elements that are in conformational contact with FOXA2. Our data suggests that the deletions in these three children may cause disease through the dysregulation of FOXA2 expression. These findings provide new insights into the regulation of FOXA2 in the beta-cell and confirm an aetiological role for chromosome 20p11.2 deletions in syndromic HI.

Evolution of pleiotropic costs in experimental populations.

The fitness of populations adapting to new environments is expected to decline in different environments, but empirical studies often do not lend support for such adaptation costs. We test the idea that the initial fitness of the selected populations in the environment where the cost is estimated is key for interpreting tests of ecological trade-offs. We isolated single clones of the yeast Saccharomyces cerevisiae every ~250 generations from replicate experimental lineages that had been selected during 5000 generations in a glucose-limited environment. We then selected these clones in a galactose-limited environment for ~120 generations. Finally, we estimated single-clone fitness in both environments, before and after selection on galactose. The pleiotropic effects on glucose of selection on galactose evolved from positive to negative as fitness in glucose increased, providing strong support for the importance of initial fitness for determining the sign and magnitude of pleiotropic effects. This demonstrates that the sign of pleiotropic effects for fitness following adaptation to a new environment can change during long-term adaptation to an original environment. We also found no relationship between the size of the fitness changes in galactose and glucose, such that pleiotropic effects in glucose became relatively smaller as the sizes of direct effects on galactose increased.

Ultracision versus electrocautery in performing modified radical mastectomy and axillary lymph node dissection for breast cancer: a prospective randomized control trial.

BACKGROUND: Treatment for breast cancer has improved dramatically over the decades. Nevertheless, modified radical mastectomy with axillary dissection remains the standard treatment for most patients, especially those with big tumours. The conventional technology is to use diathermy to cut and coagulate blood vessels. The Ultracision dissector has been widely used in laparoscopic surgery and is documented to be safe and fast for cutting and coagulating tissue. The aim of this study is to compare ultracision to electrocautery, looking in terms of amount of post operative drainage, duration of drain days, seroma formation and other complications. METHODOLOGY: This study was a prospective randomized control trial of modified radical mastectomy performed for breast cancer in Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM) between 1st June 2007 to 31st December 2008. Patients were randomized in two groups: group A (n = 20) underwent modified radical mastectomy using ultracision (UC) and group B (n = 20) with the conventional electrocautery (EC) method. Main outcome measures were amount of drainage and duration of drain days. An unpaired 2-tailed Student's t test and the χ2 test to compare the groups. RESULTS: A total of 40 patients were involved in this study. The majority of patients were Malay (55%) followed by Chinese (35%), Indian (5%) and others (5%). The mean volume of drainage from the axilla in the EC group was significantly higher than UC group [489.5 versus 188.1 mls (p < 0.001)]. The mean volume of drainage from the breast and the total drainage from both the breast and axilla was also significantly higher in the EC group compared to UC [169.3 versus 58.8 mls (p = 0.004) and 663.7 versus 247.0 mls (p < 0.002) respectively]. The drainage consequently showed significant reduction in terms of drain days in the axilla [6 days versus 3 days (p < 0.002)] and the breast [3 days versus 2 days (p < 0.002)] in the UC compared to the EC. There was no significant complication in both arms. In conclusion, the use of ultracision able to reduce the amount of drainage and the number of drain days after performing modified radical mastectomy. In doing so, the use of this technology enable us to discharge patients earlier without significant morbidities.

Hyperinsulinemic Hypoglycemia Diagnosed in Childhood Can Be Monogenic.

CONTEXT: Congenital hyperinsulinism (HI) is characterized by inappropriate insulin secretion despite low blood glucose. Persistent HI is often monogenic, with the majority of cases diagnosed in infancy. Less is known about the contribution of monogenic forms of disease in those presenting in childhood. OBJECTIVE: We investigated the likelihood of finding a genetic cause in childhood-onset HI and explored potential factors leading to later age at presentation of disease. METHODS: We screened known disease-causing genes in 1848 individuals with HI, referred for genetic testing as part of routine clinical care. Individuals were classified as infancy-onset (diagnosed with HI < 12 months of age) or childhood-onset (diagnosed at age 1-16 years). We assessed clinical characteristics and the genotypes of individuals with monogenic HI diagnosed in childhood to gain insights into the later age at diagnosis of HI in these children. RESULTS: We identified the monogenic cause in 24% (n = 42/173) of the childhood-onset HI cohort; this was significantly lower than the proportion of genetic diagnoses in infancy-onset cases (74.5% [n = 1248/1675], P < 0.00001). Most (75%) individuals with genetically confirmed childhood-onset HI were diagnosed before 2.7 years, suggesting these cases represent the tail end of the normal distribution in age at diagnosis. This is supported by the finding that 81% of the variants identified in the childhood-onset cohort were detected in those diagnosed in infancy. CONCLUSION: We have shown that monogenic HI is an important cause of hyperinsulinism presenting outside of infancy. Genetic testing should be considered in children with persistent hyperinsulinism, regardless of age at diagnosis.

Brixia Chest X-ray Score, Laboratory Parameters and Vaccination Status for Prediction of Mortality in COVID-19 Hospitalized Patients.

Chest X-ray has verified its role as a crucial tool in COVID-19 assessment due to its practicability, especially in emergency units, and Brixia score has proven as a useful tool for COVID-19 pneumonia grading. The aim of our study was to investigate correlations between main laboratory parameters, vaccination status, and Brixia score, as well as to confirm if Brixia score is a significant independent predictor of unfavorable outcome (death) in COVID-19 patients. The study was designed as a cross-sectional multicentric study. It included patients with a diagnosed COVID-19 infection who were hospitalized. This study included a total of 279 patients with a median age of 62 years. The only significant predictor of unfavorable outcome (death) was Brixia score (adjusted odds ratio 1.148, p = 0.022). In addition, the results of the multiple linear regression analysis (R2 = 0.334, F = 19.424, p < 0.001) have shown that male gender (B = 0.903, p = 0.046), severe COVID-19 (B = 1.970, p < 0.001), and lactate dehydrogenase (B = 0.002, p < 0.001) were significant positive predictors, while albumin level (B = -0.211, p < 0.001) was a significant negative predictor of Brixia score. Our results provide important information about factors influencing Brixia score and its usefulness in predicting the unfavorable outcome (death) of COVID-19 patients. These findings have clinical relevance, especially in epidemic circumstances.

A Retrospective Analysis of the Effects of Time on Compliance and Driving Pressures in ARDS.

BACKGROUND: The evolution of compliance and driving pressure in ARDS and the effects of time spent on noninvasive respiratory support prior to intubation have not been well studied. We conducted this study to assess the effect of the duration of noninvasive respiratory support prior to intubation (ie, noninvasive ventilation [NIV], high-flow nasal cannula [HFNC], or a combination of NIV and HFNC) on static compliance and driving pressure and retrospectively describe its trajectory over time for COVID-19 and non-COVID-19 ARDS while on mechanical ventilation. METHODS: This is a retrospective analysis of prospectively collected data from one university-affiliated academic medical center, one rural magnet hospital, and 3 suburban community facilities. A total of 589 subjects were included: 55 COVID-19 positive, 137 culture positive, and 397 culture-negative subjects. Static compliance and driving pressure were calculated at each 8-h subject-ventilator assessment. RESULTS: Days of pre-intubation noninvasive respiratory support were associated with worse compliance and driving pressure but did not moderate any trajectory. COVID-19-positive subjects showed non-statistically significant worsening compliance by 0.08 units per subject-ventilator assessment (P = .24), whereas COVID-19-negative subjects who were either culture positive or negative showed statistically significant improvement (0.12 and 0.18, respectively; both P < .05); a statistically similar but inverse pattern was observed for driving pressure. CONCLUSIONS: In contrast to non-COVID-19 ARDS, COVID-19 ARDS was associated with a more ominous trajectory with no improvement in static compliance or driving pressures. Though there was no association between days of pre-intubation noninvasive respiratory support and mortality, its use was associated with worse overall compliance and driving pressure.

Fibroblastic rheumatism: a report of 4 cases with potential therapeutic implications.

BACKGROUND: Fibroblastic rheumatism is a rare dermatoarthropathy characterized by the sudden onset of cutaneous nodules, flexion contractures, and polyarthritis. Histopathology in the correct clinical context confirms the diagnosis. Treatment is based on observational data from single case reports. OBJECTIVE: We describe 4 cases, review histologic findings, and discuss therapeutic responses. METHODS: Cases coded as fibroblastic rheumatism were retrieved from institutional and consultation files. Medical charts and biopsy specimens were reviewed. Elastic stains and immunostains for smooth muscle actin, S100, CD34, desmin, and epithelial membrane antigen were performed on selected cases. RESULTS: Four cases were identified. Patients displayed cutaneous nodules and arthralgias. Flexion contractures/decreased motion were present in two patients; one patient had associated Raynaud phenomenon and erosive joint disease. Biopsy specimens demonstrated a fibroblastic proliferation associated with a collagenous stroma. Growth patterns varied from cellular fascicles to paucicellular randomly arranged spindle cells. Elastic fibers were absent in all cases tested (3/3). Immunohistochemical stains demonstrated immunoreactivity for smooth muscle actin in one of 3 cases in a myofibroblastic pattern. Other stains were negative. One patient had complete resolution of disease with methotrexate. One patient partially responded to interferon-alfa and ribavirin and was subsequently treated with methotrexate with additional improvement. One patient had limited response to all therapies attempted. One patient was lost to follow-up. LIMITATIONS: Small sample size (n = 4) is a limitation. CONCLUSION: Our data expand the clinical, histologic, and therapeutic response data on fibroblastic rheumatism. Correlation with clinical history is critical to avoid misdiagnosis as other fibrosing lesions. Methotrexate and interferon-alfa are potential therapies.

Transformation of Biopharmaceutical Manufacturing Through Single-Use Technologies: Current State, Remaining Challenges, and Future Development.

Single-use technologies have transformed conventional biopharmaceutical manufacturing, and their adoption is increasing rapidly for emerging applications like antibody-drug conjugates and cell and gene therapy products. These disruptive technologies have also had a significant impact during the coronavirus disease 2019 pandemic, helping to advance process development to enable the manufacturing of new monoclonal antibody therapies and vaccines. Single-use systems provide closed plug-and-play solutions and enable process intensification and continuous processing. Several challenges remain, providing opportunities to advance single-use sensors and their integration with single-use systems, to develop novel plastic materials, and to standardize design for interchangeability. Because the industry is changing rapidly, a holistic analysis of the current single-use technologies is required, with a summary of the latest advancements in materials science and the implementation of these technologies in end-to-end bioprocesses.

Amyloidosis Cutis Dyschromica in a 16-Year-Old Filipino Girl: A Case Report.

Amyloidosis cutis dyschromica is a rare variant of primary cutaneous amyloidosis characterized by hyper- and hypopigmented macules. In this paper, we reported a case of a 16-year-old Filipino girl with hyper- and hypopigmented to depigmented macules on the upper and lower extremities, which started when she was 9 years of age.

Non-coding variants disrupting a tissue-specific regulatory element in HK1 cause congenital hyperinsulinism.

Gene expression is tightly regulated, with many genes exhibiting cell-specific silencing when their protein product would disrupt normal cellular function1. This silencing is largely controlled by non-coding elements, and their disruption might cause human disease2. We performed gene-agnostic screening of the non-coding regions to discover new molecular causes of congenital hyperinsulinism. This identified 14 non-coding de novo variants affecting a 42-bp conserved region encompassed by a regulatory element in intron 2 of the hexokinase 1 gene (HK1). HK1 is widely expressed across all tissues except in the liver and pancreatic beta cells and is thus termed a 'disallowed gene' in these specific tissues. We demonstrated that the variants result in a loss of repression of HK1 in pancreatic beta cells, thereby causing insulin secretion and congenital hyperinsulinism. Using epigenomic data accessed from public repositories, we demonstrated that these variants reside within a regulatory region that we determine to be critical for cell-specific silencing. Importantly, this has revealed a disease mechanism for non-coding variants that cause inappropriate expression of a disallowed gene.

Sex differences in expression and subcellular localization of heart rhythm determinant proteins.

To evaluate sex differences in protein expression in the heart, we performed Western blot studies on a subset of Heart Rhythm Determinant (HRD) proteins. We examined key components of a variety of types of mechanical and electrical junctions including, connexin43, plakophilin-2, N-cadherin and plakoglobin, ankyrin-2 and actin. We describe novel findings in sex differences in cardiac protein expression and membrane localization. For most proteins examined, sex differences were significantly more pronounced in the membrane compartment than in overall expression. These studies extend our previous findings in microarray studies to demonstrate that sex differences in gene expression are likely to confer distinct functional properties on male and female myocardium.

Postobstructive regeneration of kidney is derailed when surge in renal stem cells during course of unilateral ureteral obstruction is halted.

Unilateral ureteral obstruction (UUO), a model of tubulointerstitial scarring (TIS), has a propensity toward regeneration of renal parenchyma after release of obstruction (RUUO). No information exists on the contribution of stem cells to this process. We performed UUO in FVB/N mice, reversed it after 10 days, and examined kidneys 3 wk after RUUO. UUO resulted in attenuation of renal parenchyma. FACS analysis of endothelial progenitor (EPC), mesenchymal stem (MSC) and hematopoietic stem (HSC) cells obtained from UUO kidneys by collagenase-dispersed single-cell suspension showed significant increase in EPC, MSC, and HSC compared with control. After RUUO cortical parenchyma was nearly restored, and TIS score improved by 3 wk. This reversal process was associated with return of stem cells toward baseline level. When animals were chronically treated with nitric oxide synthase (NOS) inhibitor at a dose that did not induce hypertension but resulted in endothelial dysfunction, TIS scores were not different from control UUO, but EPC number in the kidney decreased significantly; however, parenchymal regeneration in these mice was similar to control. Blockade of CXCR4-mediated engraftment resulted in dramatic worsening of UUO and RUUO. Similar results were obtained in caveolin-1-deficient but not -overexpressing mice, reflecting the fact that activation of CXCR4 occurs in caveolae. The present data show increase in EPC, HSC, and MSC population during UUO and a tendency for these cells to decrease to control level during RUUO. These processes are minimally affected by chronic NOS inhibition. Blockade of CXCR4-stromal cell-derived factor-1 (SDF-1) interaction by AMD3100 or caveolin-1 deficiency significantly reduced the UUO-associated surge in stem cells and prevented parenchymal regeneration after RUUO. We conclude that the surge in stem cell accumulation during UUO is a prerequisite for regeneration of renal parenchyma.