Impact of diabetes on COVID-19 patient health outcomes in a vulnerable racial minority community.

BACKGROUND: Diabetes is a growing health concern in the United States and especially New York City. New York City subsequently became an epicenter for the coronavirus pandemic in the Spring of 2020. Previous studies suggest that diabetes is a risk factor for adverse outcomes in COVID-19. OBJECTIVE: To investigate the association between diabetes and COVID-19 outcomes as well as assess other covariates that may impact health outcomes. DESIGN: Retrospective cohort study of COVID-19 hospitalized patients from March to May, 2020. PARTICIPANTS: In total, 1805 patients were tested for COVID-19 and 778 tested positive for COVID-19. Patients were categorized into 2 groups: diabetes (measured by an Hba1c >6.5 or had a history of diabetes) and those without diabetes. RESULTS: After controlling for other comorbidities, diabetes was associated with increased risk of mortality (aRR = 1.28, 95% CI 1.03-1.57, p = 0.0231) and discharge to tertiary care centers (aRR = 1.69, 95% CI 1.04-2.77, p = 0.036). compared to non-diabetes. Age and coronary artery disease (CAD) increased the risk of mortality among diabetic patients compared to patients with diabetes alone without CAD or advanced age. The diabetes cohort had more patients with resolving acute respiratory failure (62.2%), acute kidney injury secondary to COVID-19 (49.0%) and sepsis secondary to COVID-19 (30.1%). CONCLUSION: This investigation found that COVID-19 patients with diabetes had increased mortality, multiple complications at discharge, and increased rates of admission to a tertiary care center than those without diabetes suggesting a more severe and complicated disease course that required additional services at time of discharge.

Successful in vitro fertilization following conservative surgery for synchronous endometrioid tumor of ovary and uterus.

BACKGROUND: Successful pregnancy outcome in women with synchronous ovarian and endometrial cancers is very rare. We report successful pregnancy outcome in a young woman managed conservatively for synchronous endometrial and ovarian cancer. CASE PRESENTATION: Thirty years old nulliparous lady presented following exploratory laparotomy, left salpingo-oophorectomy and hysteroscopic polypectomy for left adnexal mass. Histology revealed endometrioid carcinoma of left ovary and moderately differentiated adenocarcinoma in the resected polyp. She underwent staging laparotomy along with hysteroscopy which confirmed above findings without any evidence of further tumor spread. She was treated conservatively with high dose oral progestin (megestrol acetate, 160 mg) and leuprolide acetate 3.75 mg monthly injections for three months along with four cycles of carboplatin and paclitaxel based chemotherapy followed by monthly injection of leuprolide for further three months. After failure of spontaneous conception, she underwent ovulation induction for six cycles along with intrauterine insemination which failed. She underwent in vitro fertilization with donor egg followed by elective cesarean section at 37 weeks of gestation. She delivered a healthy baby of weight 2.7 kg. Intraoperatively 5 × 6 cm right ovarian cyst was found which drained chocolate coloured fluid on puncture and cystectomy was carried out. Histological examination revealed endometrioid cyst of right ovary. Uterus was spared as she wanted to preserve her fertility. She is being followed periodically and is normal nine months following delivery. She is on injection Depot medroxy progesterone acetate once every three months.

Adenosarcoma of the uterine cervix with heterologous elements: a case report and review of literature.

INTRODUCTION: Adenosarcoma of the uterus is a rare tumor composed of benign epithelial and malignant stromal components, usually encountered in young women. Till date, more than 100 cases of mullerian adenosarcoma of the cervix with homologous elements have been reported. However, only 15 cases of mullerian adenosarcoma of the cervix with heterologous elements are reported. MATERIALS AND METHODS: We describe a case of mullerian adenosarcoma with heterologous elements of rhabdomyosarcoma and benign cartilage presenting as a cervical polyp in a young girl. The clinicopathological features and management of this rare entity is reviewed. CONCLUSION: Cervical adenosarcomas are rare tumors that may appear in reproductive age. Optimal therapy is still unclear, and a long-term follow-up is essential. Such cases need to be reported as accumulation of individual cases will be able to provide knowledge about its optimal therapy and prognosis.

Morphologic and Immunocytochemical Features of High-Grade Serous Carcinoma of Ovary in Ascitic Fluid Effusion and Fine-Needle Aspiration Cytology.

OBJECTIVES: High-grade serous carcinoma (HGSC) is the most common ovarian malignancy. The role of cytopathology in obtaining tissue diagnosis before institution of neoadjuvant chemotherapy (NACT) was evaluated. METHODS: All histopathology-proven HGSC specimens between 2015 and 2018 with prior cytopathologic diagnosis by ascitic fluid evaluation or fine-needle aspiration (FNA) of ovarian mass were reviewed with cell block immunocytochemistry for CK7, CK20, PAX8, WT1, and p53. RESULTS: Of 288 cases of HGSC, pre-NACT cytology diagnosis was established in 32% (93/288), with specific HGSC diagnoses made on ascitic fluid in 88% (82/93) and by ovarian mass FNA in 12% (11/93). The ascitic fluid showed moderate/high cellularity with papillary clusters in 76% (71/93) cases. Cell block immunocytochemistry showed tumor cells positive for CK7, PAX8, and WT1. p53 showed mutant or null-type positivity in 65% (33/51) and 33% (17/51) of cases, respectively, with 100% concordance with subsequent histopathology specimens. Poor/intermediate response to chemotherapy was shown in 75% of cases. CONCLUSIONS: Combined assessment of cytomorphology, cell block histomorphology, and ancillary immunohistochemical testing, including PAX8, WT1, and p53, allows for specific pre-NACT diagnoses of HGSC in ascitic fluid and ovarian FNA cytology. This practice allows for initiation of chemotherapy and diminution of disease burden prior to definitive surgical therapy.

Activation of pedunculopontine tegmental protein kinase A: a mechanism for rapid eye movement sleep generation in the freely moving rat.

Cells in the pedunculopontine tegmentum (PPT) play a key role in the generation of rapid eye movement (REM) sleep, but its intracellular signaling mechanisms remain unknown. In the current studies, the role of PPT intracellular protein kinase A (PKA) in the regulation of REM sleep was evaluated by comparing PKA subunit [catalytic (PKA(C alpha)) and regulatory (PKA(RI), PKA(RII alpha), and PKA(RII beta)) types] expression and activity in the PPT at normal, high, and low REM sleep conditions. To compare anatomical specificity, REM sleep-dependent expressions of these PKA subunits were also measured in the medial pontine reticular formation (mPRF), medial prefrontal cortex (mPFC), and anterior hypothalamus (AHTh). The results of these PKA subunit expression and activity studies demonstrated that the expression of PKA(C alpha) and PKA activity in the PPT increased and decreased during high and low REM sleep, respectively. Conversely, PKA(C alpha) expression and PKA activity decreased with high REM sleep in the mPRF. Expression of PKA(C alpha) also decreased in the mPFC and remained unchanged in the AHTh with high REM sleep. These subunit expression and PKA activity data reveal a positive relationship between REM sleep and increased PKA activity in the PPT. To test this molecular evidence, localized activation of cAMP-dependent PKA activity was blocked using a pharmacological technique. The results of this pharmacological study demonstrated that the localized inhibition of cAMP-dependent PKA activation in the PPT dose-dependently suppressed REM sleep. Together, these results provide the first evidence that the activation of the PPT intracellular PKA system is involved in the generation of REM sleep.

Parallel organization of contralateral and ipsilateral prefrontal cortical projections in the rhesus monkey.

BACKGROUND: The neocortical commissures have a fundamental role in functional integration across the cerebral hemispheres. We investigated whether commissural projections in prefrontal cortices are organized according to the same or different rules as those within the same hemisphere, by quantitatively comparing density, topography, and laminar origin of contralateral and ipsilateral projections, labeled after unilateral injection of retrograde tracers in prefrontal areas. RESULTS: Commissural projection neurons constituted less than one third of the ipsilateral. Nevertheless, projections from the two hemispheres were strongly correlated in topography and relative density. We investigated to what extent the distribution of contralateral projections depended on: (a) geographic proximity of projection areas to the area homotopic to the injection site; (b) the structural type of the linked areas, based on the number and neuronal density of their layers. Although both measures were good predictors, structural type was a comparatively stronger determinant of the relative distribution and density of projections. Ipsilateral projection neurons were distributed in the superficial (II-III) and deep (V-VI) layers, in proportions that varied across areas. In contrast, contralateral projection neurons were found mostly in the superficial layers, but still showed a gradient in their distribution within cortical layers that correlated significantly with cortical type, but not with geographic proximity to the homotopic area. CONCLUSION: The organization of ipsilateral and contralateral prefrontal projections is similar in topography and relative density, differing only by higher overall density and more widespread laminar origin of ipsilateral than contralateral projections. The projections on both sides are highly correlated with the structural architecture of the linked areas, and their remarkable organization is likely established by punctuated development of distinct cortical types. The preponderance of contralateral projections from layer III may be traced to the late development of the callosal system, whose function may be compromised in diseases that have their root late in ontogeny.

Role of neuropeptide Y (NPY) in the regulation of reproduction: study based on catfish model.

Significance of NPY in the regulation of GnRH-LH axis was evaluated. Considerable NPY immunoreactivity was seen in the components like olfactory system, basal telencephalon, preoptic and tuberal areas, and the pituitary gland that serve as neuroanatomical substrates for processing reproductive information. Close anatomical association as well as colocalizations of NPY and GnRH were seen in the olfactory receptor neurons, olfactory nerve fibers and their terminals in the glomeruli, ganglion cells of nervus terminalis, medial olfactory tracts, fibers in the ventral telencephalon and pituitary. In the pituitary, NPY fibers seem to innervate the GnRH as well as LH cells. Intracranial administration of NPY resulted in significant increase in the GnRH immunoreactivity in all the components of the olfactory system. In the pituitary, NPY augmented the population of GnRH fibers and LH cells. HPLC analysis showed that salmon GnRH content in the olfactory organ, bulb, preoptic area+telencephalon and pituitary was also significantly increased following NPY treatment. NPY may play a role in positive regulation of GnRH throughout the neuraxis and also up-regulate the LH cells in the pituitary.

Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression.

BACKGROUND: Experiencing emotions engages high-order orbitofrontal and medial prefrontal areas, and expressing emotions involves low-level autonomic structures and peripheral organs. How is information from the cortex transmitted to the periphery? We used two parallel approaches to map simultaneously multiple pathways to determine if hypothalamic autonomic centres are a key link for orbitofrontal areas and medial prefrontal areas, which have been associated with emotional processes, as well as low-level spinal and brainstem autonomic structures. The latter innervate peripheral autonomic organs, whose activity is markedly increased during emotional arousal. RESULTS: We first determined if pathways linking the orbitofrontal cortex with the hypothalamus overlapped with projection neurons directed to the intermediolateral column of the spinal cord, with the aid of neural tracers injected in these disparate structures. We found that axons from orbitofrontal and medial prefrontal cortices converged in the hypothalamus with neurons projecting to brainstem and spinal autonomic centers, linking the highest with the lowest levels of the neuraxis. Using a parallel approach, we injected bidirectional tracers in the lateral hypothalamic area, an autonomic center, to label simultaneously cortical pathways leading to the hypothalamus, as well as hypothalamic axons projecting to low-level brainstem and spinal autonomic centers. We found densely distributed projection neurons in medial prefrontal and orbitofrontal cortices leading to the hypothalamus, as well as hypothalamic axonal terminations in several brainstem structures and the intermediolateral column of the spinal cord, which innervate peripheral autonomic organs. We then provided direct evidence that axons from medial prefrontal cortex synapse with hypothalamic neurons, terminating as large boutons, comparable in size to the highly efficient thalamocortical system. The interlinked orbitofrontal, medial prefrontal areas and hypothalamic autonomic centers were also connected with the amygdala. CONCLUSIONS: Descending pathways from orbitofrontal and medial prefrontal cortices, which are also linked with the amygdala, provide the means for speedy influence of the prefrontal cortex on the autonomic system, in processes underlying appreciation and expression of emotions.

Neurotoxic lesions of phasic pontine-wave generator cells impair retention of 2-way active avoidance memory.

STUDY OBJECTIVES: The aim of this study was to test the hypothesis that the activation of pontine (P)-wave generator is critical for the posttraining rapid eye movement (REM) sleep-dependent memory processing. DESIGN: Ibotenic acid was microinjected (0.5 microg in 0.05 microL) into the functionally identified P-wave generator in order to destroy the cell bodies and thus to study the effects of their destruction upon waking-sleep states, P-waves, and 2-way active avoidance memory. SETTING: Sleep research laboratory at Boston University School of Medicine. PARTICIPANTS: Adult male Sprague-Dawley rats (N = 27). INTERVENTIONS: Chronically implanted for recording polygraphic signs of sleep and bilateral guide tubes for the local microinjections into the P-wave generator. MEASUREMENTS AND RESULTS: The ibotenic acid produced a small spherical area (< or = 0.35 mm in diameter) of nerve cell loss centered on the P-wave generator. Bilateral lesioning of the P-wave generator decreased P-waves during REM sleep by > 95% without significantly changing the amounts of time spent in wake, slow-wave sleep, or REM sleep. In these P-wave generator-lesioned rats, acquisition of avoidance learning and posttraining wake-sleep changes were identical to those of the sham-lesioned rats. However, in the test trials, after 6 hours of undisturbed sleep-wake, P-wave generator-lesioned rats had no retention of avoidance memory. CONCLUSIONS: These findings, for the first time, provide direct evidence that P-wave-generating cells are critical for normal REM sleep-dependent memory processing. This evidence supports our hypothesis that the P-wave generator in the brainstem may act as an on switch to provide activating input to forebrain structures for sleep-dependent memory processing.

Neuropeptide Y in the olfactory system, forebrain and pituitary of the teleost, Clarias batrachus.

Distribution of neuropeptide Y (NPY)-like immunoreactivity in the forebrain of catfish Clarias batrachus was examined with immunocytochemistry. Conspicuous immunoreactivity was seen in the olfactory receptor neurons (ORNs), their projections in the olfactory nerve, fascicles of the olfactory nerve layer in the periphery of bulb and in the medial olfactory tracts as they extend to the telencephalic lobes. Ablation of the olfactory organ resulted in loss of immunoreactivity in the olfactory nerve layer of the bulb and also in the fascicles of the medial olfactory tracts. This evidence suggests that NPY may serve as a neurotransmitter in the ORNs and convey chemosensory information to the olfactory bulb, and also to the telencephalon over the extrabulbar projections. In addition, network of beaded immunoreactive fibers was noticed throughout the olfactory bulb, which did not respond to ablation experiment. These fibers may represent centrifugal innervation of the bulb. Strong immunoreactivity was encountered in some ganglion cells of nervus terminalis. Immunoreactive fibers and terminal fields were widely distributed in the telencephalon. Several neurons of nucleus entopeduncularis were moderately immunoreactive; and a small population of neurons in nucleus preopticus periventricularis was also labeled. Immunoreactive terminal fields were particularly conspicuous in the preoptic, the tuberal areas, and the periventricular zone around the third ventricle and inferior lobes. NPY immunoreactive cells and fibers were detected in all the lobes of the pituitary gland. Present results describing the localization of NPY in the forebrain of C. batrachus are in concurrence with the pattern of the immunoreactivity encountered in other teleosts. However, NPY in olfactory system of C. batrachus is a novel feature that suggests a role for the peptide in processing of chemosensory information.

Calcitonin-like immunoreactivity in the subcommissural organ-Reissner's fiber complex of some freshwater and marine teleosts.

The subcommissural organ (SCO) is a highly specialised circumventricular ependymal organ covering and penetrating the posterior commissure. The secretory products of the SCO condense to form Reissner's fiber (RF). Because of its extensive secretory activity and the chemical properties of its secretion, the organ functions as similar to the neurosecretory cells. Teleosts comprised of more than 20,000 extant species that show great diversity in terms of the form, habit and habitat. Affinity of calcitonin antibodies for the SCO-RF complex was used as a histochemical tool to study the morphology of some freshwater and seawater teleosts and its potential correlate to their osmotic environment. While intense to moderate calcitonin-like immunoreactivity was seen in the cells of the SCO of majority of the freshwater species viz., common carp, catfish, eel and perch; the SCO of goldfish revealed limited immunoreactivity. Like the SCO, the RF in all species was also immunostained with antibodies against calcitonin. It appeared as a single, continuous fiber that ran from SCO into the third ventricle and extended through the aqueduct, fourth ventricle and central canal of the spinal cord. In contrast to that in the freshwater fishes, the SCO-RF complex in majority of the seawater fishes, showed no calcitonin-like immunoreactivity. The data presented in this study described the comparative histomorphology of the SCO-RF complex and suggest a possibility that the calcitonin-like immunoreactivity in the SCO-RF complex might be a feature correlated to the osmotic environment of the fish.

Vitamin C and E supplementation does not reduce the risk of superimposed PE in pregnancy.

BACKGROUND: Oxidative stress could play a role in the development of preeclampsia. There is some evidence to suggest that vitamin C and E supplements can reduce the risk of the disorder. We hypothesized its beneficial role in a group of pregnant women with essential hypertension. METHODS: In this randomized controlled trial, we enrolled 50 pregnant women with essential hypertension. We assigned the women 1000 mg vitamin C and 400 IU natural vitamin E (RRR α tocopherol; n = 25), daily from the second trimester of pregnancy until delivery or no supplementation (n = 25). Our primary endpoint was development of superimposed preeclampsia, and main secondary endpoints were aggravation of hypertension, need for admission, need to increase antihypertensive drugs, and small size for gestational age (

In vitro effects of peroxisome proliferator-activated receptor-γ ligands on gene expression in lipopolysaccharide-induced endometrial and endometriotic stromal cells.

This in vitro study demonstrates the comparative anti-inflammatory effects of rosiglitazone and 15d-PGJ(2) in endometriosis and provides evidence for exploitation of peroxisome proliferator-activated receptor-γ as a therapeutic target.

Renal hematoma: an unusual cause of acute abdomen and fetal demise in severe pre-eclampsia.

Retroperitoneal hematoma occurs rarely in an obstetric patient. Renal hematoma may present with signs and symptoms, which may mimic the clinical presentation of abruptio placentae or rupture uterus. Although renal hematoma is sometimes a surgical emergency due to hypovolemic shock, conservative management by angiographic embolization may be done. Timely diagnosis and management is required to decrease the maternal mortality and morbidity. We hereby report a case of spontaneous renal hematoma in a patient with severe pre-eclampsia who presented with acute abdomen and intrauterine fetal death.

Implication of the RAGE-EN-RAGE axis in endometriosis.

OBJECTIVE: To investigate the involvement of the receptor gene for advanced glycation (RAGE), its ligand EN-RAGE, and COX-2 in endometriosis. METHODS: The mRNA and protein expression of the corresponding genes were determined from endometriotic cells from 28 study patients and healthy endometrial stromal cells from 20 controls by semiquantitative RT-PCR and Western blot analysis, respectively, using beta-actin as an invariant control. RESULTS: The expression of COX-2, RAGE, and EN-RAGE was significantly increased, as evidenced by the significantly greater mRNA and protein expression in the cells of the study patients (P<0.001). Previous treatment for endometriosis did not lessen mRNA and protein expression (P<0.001). CONCLUSION: Our findings strengthen the hypothesis of an underlying inflammation in the pathophysiology of endometriosis and suggest exploring anti-inflammatory therapies as adjunct treatment.

Role of 8-iso-prostaglandin F2alpha and 25-hydroxycholesterol in the pathophysiology of endometriosis.

OBJECTIVE: To investigate the involvement of 8-iso-PGF(2alpha) and 25-hydroxycholesterol (25-OH-Chol) in the pathophysiology of endometriosis. DESIGN: Observational case-control study using enzyme immunoassay and high-performance liquid chromatography (HPLC). SETTING: Postgraduate Institute of Medical Education and Research. PATIENT(S): Forty-five women undergoing laparoscopy (n = 25), laparotomy (n = 19), or tubal ligation (n =1). INTERVENTION(S): Venipuncture and laparoscopic peritoneal fluid (PF) collection. MAIN OUTCOME MEASURE(S): The levels of 8-iso-PGF(2alpha) were determined both in urine and PF of all the patients using enzyme immunoassay. The levels of 25-OH-Chol were determined by using reversed phase HPLC both in the plasma and PF samples. Oxidative damage to DNA was assessed by agarose gel electrophoresis. RESULT(S): Significantly increased levels of 8-iso-PGF(2alpha) were observed both in urine and PF of women with endometriosis compared with control women. Similarly, higher levels of 25-OH-Chol were observed both in plasma and PF of patients compared with controls and the difference was statistically significant. A clear-cut tailing pattern was observed in DNA of patients with endometriosis, indicating significant DNA damage. CONCLUSION(S): Our observations implicate oxidative stress in the pathophysiology of endometriosis. For the first time, we demonstrate that 8-iso-PGF(2alpha) and oxysterols (the known promoters of steroidogenesis) might be the culprits in this disease.

In vitro effects of atorvastatin on lipopolysaccharide-induced gene expression in endometriotic stromal cells.

OBJECTIVE: To investigate the in vitro effects of atorvastatin on lipopolysaccharide (LPS)-induced gene expression in endometrial-endometriotic stromal cells. DESIGN: In vitro experimental study using flow cytometry, ELISA, semiquantitative reverse transcriptase polymerase chain reaction, and Western blot. SETTING: Postgraduate Institute of Medical Education and Research. PATIENT(S): Twenty-five women undergoing laparoscopy (n = 10) and laparotomy (n = 15). INTERVENTION(S): Endometriotic cyst wall (group I) and endometrial biopsy (group II) collection. MAIN OUTCOME MEASURE(S): The endometrial-endometriotic stromal cells were isolated from ectopic (group I) and eutopic (group II) endometrium by established methods, cultured, and stimulated with LPS (1 µg/mL), followed by atorvastatin treatment in a time- and dose-dependent manner to investigate the effects of LPS on proliferation (Ki-67) and expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), receptor for advanced glycation end products (RAGE), extracellular newly identified RAGE binding protein (EN-RAGE), peroxisome proliferator activated receptor-γ (PPAR-γ), and liver X receptor-α (LXR-α) genes in endometrial-endometriotic stromal cells and on levels of insulin-like growth factor binding protein-1 (IGFBP-1) and 17ß-E(2) in endometrial-endometriotic stromal cell culture supernatant. RESULT(S): Significant inhibition of Ki-67 and LPS-induced expression of inflammatory and angiogenic genes (COX-2, VEGF, RAGE, and EN-RAGE) was observed in atorvastatin-treated endometrial-endometriotic stromal cells. In contrast, a significant dose- and time-dependent increase in expression of anti-inflammatory genes (PPAR-γ and LXR-α) and levels of IGFBP-1 was observed after atorvastatin treatment in both the groups. However, atorvastatin treatment had no effect on 17ß-E(2) levels in endometrial/endometriotic stromal cell culture supernatant. CONCLUSION(S): The data of the present study provide new insights for the implication of atorvastatin treatment for endometriosis in humans.

Cervical cytology in patients with postmenopausal bleeding.

In this study, the role of cervical cytology in the diagnosis of post or perimenopausal (PM) bleeding was explored. A total of 135 patients with PM bleeding were selected. In all these cases both conventional cervical cytology and histopathology follow up were available. The commonest causes of postmenopausal (PM) bleeding with abnormal histopathology were squamous cell carcinoma of cervix (14), endocervical polyp (13), endometrial adenocarcinomas (13) and simple hyperplasia without atypia (13). There were a total 13 cases of endometrial adenocarcinoma and cervical smears of these cases were reported as high grade squamous intra epithelial lesion (1), presence of endometrial cells (4), unsatisfactory due to low cellularity (2), and within normal limit (6). In brief, endometrial carcinoma and hyperplasia are the predominant causes of PM bleeding due to endometrial pathology. The presence of benign looking endometrial cells with PM bleeding always indicates a careful work upto exclude endometrial pathology.

Glial growth factor 2 promotes functional recovery with treatment initiated up to 7 days after permanent focal ischemic stroke.

Neuregulins are a family of growth factors essential for normal cardiac and nervous system development. The EGF-like domain of neuregulins contains the active site which binds and activates signaling cascades through ErbB receptors. A neuregulin-1 gene EGF-like fragment demonstrated neuroprotection in the transient middle cerebral artery occlusion (MCAO) stroke model and drastically reduced infarct volume (Xu et al., 2004). Here we use a permanent MCAO rat model to initially compare two products of the neuregulin-1 gene and also assess levels of recovery with acute versus delayed time to treatment. In the initial study full-length glial growth factor 2 (GGF2) and an EGF-like domain fragment were compared with acute intravenous delivery. In a second study GGF2 only was delivered starting at 24h, 3 days or 7 days after permanent ischemia was induced. In both studies daily intravenous administration continued for 10 days. Recovery of neurological function was assessed using limb placing and body swing tests. GGF2 had similar functional improvements compared to the EGF-like domain fragment at equimolar doses, and a higher dose of GGF2 demonstrated more robust functional improvements compared to a lower dose. GGF2 improved sensorimotor recovery with all treatment paradigms, even enhancing recovery of function with a delay of 7 days to treatment. Histological assessments did not show any associated reduction in infarct volume at either 48 h or 21 days post-ischemic event. Neurorestorative effects of this kind are of great potential clinical importance, given the difficulty of delivering neuroprotective therapies within a short time after an ischemic event in human patients. If confirmed by additional work including additional data on mechanism(s) of improved outcome with verification in other stroke models, one can make a compelling case to bring GGF2 to clinical trials as a neurorestorative approach to improving outcome following stroke injury.