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SUMMARY Skilled movements rely on a coordinated cortical and subcortical network, but how this network supports motor recovery after stroke is unknown. Previous studies focused on the perilesional cortex (PLC), but precisely how connected subcortical areas reorganize and coordinate with PLC is unclear. The dorsolateral striatum (DLS) is of interest because it receives monosynaptic inputs from motor cortex and is important for learning and generation of fast reliable actions. Using a rat focal stroke model, we perform chronic electrophysiological recordings in motor PLC and DLS during long-term recovery of a dexterous skill. We find that recovery is associated with the simultaneous emergence of reliable movement-related single-trial ensemble spiking in both structures along with increased cross-area alignment of spiking. Our study highlights the importance of consistent neural activity patterns across brain structures during recovery and suggests that modulation of cross-area coordination can be a therapeutic target for enhancing motor function post-stroke., In brief Guo et al. find that recovery of movement control after motor cortical stroke is associated with reliable neural activation and coordinated activity in both perilesional cortex (PLC) and dorsolateral striatum (DLS). Neural organization occurs simultaneously in PLC and DLS. Their results highlight the importance of distributed network changes after stroke., Graphical Abstract

Sleep is known to be important for promoting recovery after brain injuries such as stroke. Yet, it remains unclear how such injuries affect neural processing during sleep and how to precisely enhance sleep-dependent memory processing during recovery. Using an experimental model of focal cortical stroke in rats along with long-term electrophysiological monitoring of neural firing and sleep microarchitecture, here we show that sleep-dependent neural processing is altered after stroke induction. Specifically, we found that the precise coupling of spindles to global slow- oscillations (SO), a phenomenon that is known to be important for memory consolidation, appeared to be disrupted by a pathological increase in “isolated” local delta waves. The transition from this pathological to a more physiological sleep state – with both a reduction in isolated delta waves and increased spindle coupling to SO – was associated with sustained performance gains after task training during recovery. Interestingly, post-injury sleep processing could be pushed towards a more physiological state via a pharmacological reduction of tonic GABA. Together, our results suggest that sleep processing after cortical brain injuries may be impaired due to an increase in local delta waves and that restoration of physiological processing is important for recovery of task performance.

Bacterial vaginosis is a condition associated with adverse reproductive outcomes and characterized by a shift from a Lactobacillus-dominant vaginal microbiota to a polymicrobial microbiota, consistently colonized by strains of Gardnerella vaginalis. Metronidazole is the first-line treatment; however, treatment failure and recurrence rates remain high. To understand complex interactions between Gardnerella vaginalis and Lactobacillus involved in efficacy, here we develop an ordinary differential equation model that predicts bacterial growth as a function of metronidazole uptake, sensitivity, and metabolism. The model shows that a critical factor in efficacy is Lactobacillus sequestration of metronidazole, and efficacy decreases when the relative abundance of Lactobacillus is higher pre-treatment. We validate results in Gardnerella and Lactobacillus co-cultures, and in two clinical cohorts, finding women with recurrence have significantly higher pre-treatment levels of Lactobacillus relative to bacterial vaginosis–associated bacteria. Overall results provide mechanistic insight into how personalized differences in microbial communities influence vaginal antibiotic efficacy., Bacterial vaginosis (BV) is typically caused by a shift in the vaginal microbiota from a Lactobacillus-dominant community to one colonised by strains of Gardenerella vaginalis and treatment with the antibiotic metronidazole (MNZ) often results in failure and recurrence. Here, the authors use modelling and in vitro assays to show that sequestration of MNZ by Lactobacillus is critical in reducing efficacy and women with a higher pre-treatment Lactobacillus/Gardnerella ratio are more likely to recur.

Background Neo-adjuvant chemoradiotherapy reduces local recurrence in rectal cancer, but there is a paucity of evidence regarding its role for colon cancer. The aim of this study was to evaluate the feasibility and outcomes of a neo-adjuvant chemoradiotherapy (NCRT) approach for locally recurrent adherent colon cancer (LRACC). Methods All patients with non-metastatic LRACC treated with NCRT and multi-visceral resection (MVR) from January 2000 to July 2010 were included. The primary outcome was the rate of R0 resection (negative microscopic margins). Secondary outcomes were toxicities, post-operative morbidity and mortality, local recurrence, overall survival (OS) and disease-free survival (DFS). Results Fifteen patients were identified. Nine primary cancers were located in the sigmoid and 4 in the left colon. Patients were treated with 45–50 Gy in 25 daily fractions and concurrent 5-FU infusion (225 mg/m 2 /day). En-bloc MVR included between 2 and 5 adjacent organs/structures. All but two resulted in R0 resection. One patient had a complete pathologic response and one had minimal residual tumour cells in the resected specimen. Post-operative major morbidity was 33.3%. No mortality occurred. At a median follow-up of 54 months, there were 2 local, 1 regional, and 2 distant lung recurrences. No grade 3 or 4 acute or late toxicities were observed. 5-year OS and DFS were 90.0% and 63.5% respectively. Conclusions NCRT followed by MVR is a feasible option for the treatment of highly selected LRACC to achieve R0 resection, while maintaining acceptable treatment toxicity. Short-term oncological results appear satisfactory, including good local control.

Cerebral venous sinus thrombosis (CVST) is a rare and potentially deadly condition. Common etiologies include hypercoagulable diseases, low flow states, dehydration, adjacent infectious processes, oral contraceptives, hormonal replacement therapy, pregnancy, and puerperium. Symptoms include nausea, seizures, severe focal neurological deficits, coma, and headache (the most common presenting symptom). Anticoagulation is the mainstay of treatment for CVST. Transvenous clot lysis can be performed using injected thrombolytic agents and specialized catheters for clot retrieval.

Background: Compression fractures are common in patients with osteoporosis and cancer. In particular, vertebral compression fractures are crippling, and pose an additional risk of cord compression. Although a number of nonmedical options such as bracing and exercise programs may help these patients, the combination of constant, severe pain and spinal instability was until recently almost invariably synonymous with painful gradual deterioration and a poor quality of life. Vertebroplasty, and more recently kyphoplasty, are minimally invasive procedures that aim at limiting or reversing painful collapse of the vertebrae, while providing stability to the treated segment of the spine. As these new options are highly effective and involve minimal risk, it is important that physicians be familiar with them. Objective: This paper reviews the demographics of vertebral compression fractures, both osteoporotic and neoplastic, the technical aspects of vertebroplasty and kyphoplasty, and current results and outcomes. ...

Following acute multiple trauma, hypothalamic stimulation of the sympathetic nervous system and adrenal glands causes an increase in circulating corticoids and catecholamines, or a stress response. In individuals with severe traumatic brain injury or a Glasgow Coma Scale score of 3-8, this response can be exaggerated and episodic. A term commonly used by nurses caring for these individuals to describe this phenomenon is storming. Symptoms can include alterations in level of consciousness, increased posturing, dystonia, hypertension, hyperthermia, tachycardia, tachypnea, diaphoresis, and agitation. These individuals generally are at a low level of neurological activity with minimal alertness, minimal awareness, and reflexive motor response to stimulation, and the storming can take a seemingly peaceful individual into a state of chaos. Diagnosis is commonly made solely on clinical assessment, and treatment is aimed at controlling the duration and severity of the symptoms and preventing additional brain injury. Storming can pose a challenge for the nurse, from providing daily care for the individual in the height of the storming episode and treating the symptoms, to educating the family. Careful assessment of the individual leads the nurse to the diagnosis and places the nurse in the role of moderator of the storming episode, including providing treatment and evaluating outcomes.

Cancer is the hyperactive state of cell growth in which the multiplication and division of cells occur abnormally. Malignant cancer to the brain frequently begins and ends with the loss of self or quality of life. Cancer of the central nervous system can be in the form of a primary or secondary brain tumor commonly known as metastatic cancer. Primary brain tumors can be benign or malignant on the basis of the cell type or location within the brain. Metastatic cancer has a primary source of origin, from which it has traveled to the brain by direct extension (tumors arising from the skull or vertebral column), or most commonly by hematogenous spread (through the blood supply, lymphatic system, or cerebral spinal fluid). As the cancer grows, the individual can experience headache, seizures, or focal neurologic deficits, all impinging on quality of life. This article addresses malignant central nervous system cancer including metastatic cancer and malignant gliomas (anaplastic astrocytoma, grade III, and glioblastoma multiforme, grade IV). Epidemiology, diagnostic workup, treatment, and outcome also are reviewed.

Quality of life issues remain at the forefront for individuals with life-threatening disease, such as metastatic cancer. The pain of metastatic bone cancer can severely hamper an individual's quality of life. Percutaneous vertebroplasty offers a minimally invasive way to reinforce bony elements, provide substantial improvement in pain control, allow for mobilization, and overall improve quality of life in these patients.

Gossypol, a polyphenolic compound which depletes cellular energy by inhibition of several intracellular dehydrogenases, has been shown to have antiproliferative activity against human glial tumor cell lines in vitro and in nude mouse xenografts. Human trials of gossypol as a male contraceptive have demonstrated safety of long-term administration. We studied the activity of Gossypol 10 mg PO bid in 27 patients with pathologically confirmed glial tumors which had recurred after radiation therapy. Fifteen patients had glioblastoma, 11 patients anaplastic astrocytoma, 1 patient relapsed low grade glioma. Response was assessed every 8 weeks using CT/MRI scan and clinical criteria including decadron requirement. Treatment was continued until disease progression. Two patients had partial response (PR); 4 had stable disease for 8 weeks or more. One patient maintained a PR with improved KPS for 78 weeks. The other had a PR lasting 8 weeks. Toxicity was mild: 2 heavily pretreated patients had mild thrombocytopenia, 5 patients developed hypokalemia, 3 patients developed grade 2 hepatic toxicity and peripheral edema. Gossypol levels measured by HPLC did not correlate with response or toxicity in this study. We conclude that gossypol is well tolerated and has a low, but measurable, response rate in a heavily pretreated, poor-prognosis group of patients with recurrent glioma. The presumed novel mechanism of action, lack of significant myelosuppression, and activity in patients with advance glioma support further study of gossypol as an antineoplastic agent.

BACKGROUND Although it is used widely, the value of gallium imaging in managing Hodgkin's disease remains unclear. METHODS A retrospective review of gallium imaging and treatment outcome in 60 patients with Hodgkin's disease treated between January 1990 and July 1995 was conducted. The minimum follow-up was 1 year. RESULTS Based on gallium imaging, 46 patients were in complete remission (CR) after initial treatment, 10 were in partial remission (PR), and 4 had persistent or progressive disease (NR). Ten of 29 patients (34%) with gallium CR after chemotherapy subsequently recurred, compared with no recurrences in 17 patients receiving initial radiotherapy or combined chemoradiation. Eight of ten patients received further therapy after gallium PR, and nine patients remained disease free at last follow-up. Survival did not differ in patients achieving a gallium CR or PR. CONCLUSIONS Gallium-67 imaging may help confirm the presence of active Hodgkin's disease, but was unreliable in defining disease remission after chemotherapy in this study population. Patients with a gallium PR may still have a good prognosis after additional therapy. Cancer 1998;82:754-9. ©; 1998 American Cancer Society.

Absorptive hypercalciuria (a stone-forming condition) is characterized by gut hyperabsorption of calcium, hypercalciuria, and reduced bone density. Inasmuch as these features implicate enhanced calcitriol action in gut and bone, we analyzed the vitamin D receptor (VDR) gene to ascertain whether an abnormality of this gene marks patients with intestinal hyperabsorption of calcium. We have compared the frequency of a restriction fragment length polymorphism (Bsm I) associated with different alleles of the VDR gene in a group of 33 well characterized absorptive hypercalciuric patients and a group of 36 normal race- and age-matched control subjects. There was no difference between the distribution of the VDR alleles in the patient population when compared with the normal population. The coding region of VDR messenger RNA was also normal, as determined by both DNA sequence analysis and chemical mismatch cleavage analysis of copy DNA from 11 index absorptive hypercalciuric patients. On the basis of these results, we propose that the enhanced intestinal calcium absorption invariably seen in absorptive hypercalciuria and attendant symptoms of this disorder are not attributable to mutations of the VDR and are not linked to a common VDR genotype.

BACKGROUND Iproplatin (cis-dichloro-transdihydroxybis-isopropylamine platinum IV; CHIP) is a second generation cisplatin derivative that was developed to retain the antineoplastic effect of cisplatin with fewer toxic effects. Early clinical studies showed moderate activity in some neoplasms, with disappointing results in tumors of the lower gastrointestinal tract. Myelosuppression was the dose-limiting toxic effect in the acute setting. METHODS The authors report a patient with metastatic adenocarcinoma of the colon who received long-term therapy with CHIP. RESULTS The patient achieved complete remission of disease after prolonged treatment with CHIP. The patient subsequently had a myelodysplastic syndrome that rapidly transformed to acute myelogenous leukemia. CONCLUSIONS Acute leukemia may represent a late complication of CHIP therapy.

Granulocytic sarcoma is an extramedullary tumor of malignant granulocytic progenitor cells that accompanies, heralds, or signals relapse of acute myelogenous leukemia (AML), or indicates blastic transformation of a chronic myeloproliferative disorder. We describe a case involving the uterine cervix of a 51-year-old woman that led to the diagnosis of AML. Granulocytic sarcoma can occur in the female genital tract and may be the first clinically significant manifestation of a hematologic malignancy. The salient findings in 28 reported cases from 12 different countries are reviewed. Awareness of this lesion is important for all medical personnel involved in the health care of women.

Dibutyltin dichloride (DBTC) is an organotin compound used as a model for acute pancreatitis. The aim was to determine the effect of various doses of Na-selenite on the pathogenesis and course of DBTC-induced toxic changes in organs and serum of rats.Experimental pancreatitis was induced by intravenous administration of 6 mg kg(-1) BW DBTC. Na-selenite was applied as a single intravenous dose of 5 mg kg(-1) BW and as daily oral dose of 1 mg kg(-1) BW. Malondialdehyde (MDA) was detected to observe the level of oxidative stress. The tin concentration in bile and urine shows the elimination of DBTC. Organ changes were indicated by serum parameters as well as histology.DBTC causes an acute pancreatitis, cholestasis and liver lesions determined by specific elevated serum parameters and several histological lesions. Na-selenite significantly diminished MDA concentration, lipase, bilirubin and transaminases as well as organ injuries compared to only DBTC-treated rats.The treatment with Na-selenite in the scope of DBTC-induced pancreatitis points to a reduced oxidative stress characterized by diminished MDA serum levels and a milder course of pancreatitis. The generation of DBTC-Na-selenite complexes could also be a mechanism to decrease the toxicity of organotin compounds like DBTC.

Background: Aneurysms associated with vertebrobasilar fenestrations are uncommon. We report on an unusual presentation of such aneurysm with a dedicated arterial pedicle, manifesting with significant intraventricular hemorrhage. Equally important, the aneurysm was managed in a multidisciplinary fashion, which, we think, greatly contributed to a good outcome. Case Description: A 55-year-old man presented in good condition after subarachnoid and massive intraventricular hemorrhage. The aneurysm location and the extent of intraventricular hemorrhage both presented concerns regarding treatment approach. The aneurysm was first treated with transarterial coil obliteration, and intraventricular tissue plasminogen activator (tPA) infusion was given, with rapid resolution of evolving hydrocephalus. The patient had an excellent outcome. Conclusion: To our knowledge, this is the first report of a vertebrobasilar fenestration saccular aneurysm with a dedicated pedicle projecting toward the foramen of Magendie with significant intraventricular hemorrhage. In addition, this patient was successfully managed with endovascular obliteration and intraventricular tPA infusion.

Metastasis to the brain occurs in 20%–40% of cancer patients.1 About 20% of these metastases are located in the posterior fossa, cerebellum, and brainstem. Metastatic disease to periventricular brain tissue can obstruct the flow of cerebrospinal fluid (CSF) produced in the ventricles to the subarachnoid space where it is normally absorbed by arachnoid granulations. This typically causes an obstructive or non-communication hydrocephalus. A shunt has been customarily placed to drain CSF from a lateral ventricle through a pressure regulating valve and into the atrium or peritoneal or pleural cavity. Even though this technique has been successful in relieving the hydrocephalus, it has about a 50% chance of infection or failure from blockage.2 Another option for the treatment of obstructive hydrocephalus is third ventriculostomy, a minimal invasive endoscopic neurosurgical procedure. In performing third ventriculostomy, a hole is created in the floor of the third ventricle, allowing CSF inside the ventricle to drain out to the CSF space surrounding …

The puberty-controlling function of the mediocortical amygdala in immature female rats was investigated by lesioning this region at different ages and by studying the effects on the onset of spontaneous and experimentally-induced precocious puberty. At 21 days of age, bilateral lesions in the anterior mediocortical amygdala (AMCA) caused precocious puberty and enhanced the puberty-accelerating effect of bilateral lesions produced simultaneously in the medial preoptic area (MPA). Similar lesions, ineffective on day 26, delayed the onset of puberty when produced on day 32 in otherwise untreated rats. Lesions in the posterior mediocortical amygdala (PMCA) at 26 or 32 days of age postponed puberty in untreated rats and inhibited the advancement of their 1st pubertal ovulation that resulted from damage to the ventromedial-arcuate region (VAH) or daily administration of 0.05 mug estradiol benzoate (EB) per 100 g b.w. The results confirm earlier findings of different gonadotropin-controlling activities of the AMCA and PMCA in immature female rats and suggest maturational changes in the function of both areas. The gonadotropin-inhibiting action exerted by the AMCA at 3 weeks of age is lost when puberty approaches; a gonadotropin-stimulating activity seems to develop in both the AMCA and PMCA.Vaginal openings and the 1st pubertal ovulations usually occurred between 38-42 days of age in female Wistar rats. Autopsies were done on the 16th day after vaginal openings were detected, or on the day of vaginal estrus after the 1st pubertal ovulation. For daily long-term treatment with estradiol benzoate sc injections of .05 mcg were given, with higher doses as age advanced. Bilateral lesions were produced by passing an anodal DC of 1 mA through a unipolar platinum electrode. At 21 days of age, bilateral lesions in the anterior mediocortical amygdala (AMCA) caused precocious puberty and enhanced the puberty-accelerating effect of bilateral lesions produced simultaneously in the medial preoptic area. Similar lesions were ineffective on Day 26, but when produced on Day 32 they delayed the onset of puberty. Lesions of the posterior mediocortical amygdala (PMCA) at 26 or 32 days of age delayed puberty and inhibited the advancement of the 1st pubertal ovulation that had resulted from damage to the ventromedial-arcuate region, or by the daily administration of .05 mc of estradiol/benzoate/100 gm body weight. Results showed different gonadotropin-controlling activities of the AMCA and PMCA in prepubertal female rats. The gonadotropin-inhibitory action exerted by AMCA at 3 weeks of age was lost when puberty approached. Maturational changes in the function of both areas seemed to develop.