Glycogen accumulation in synaptic boutons in Clarke's nucleus neuropil after sciatic nerve crush at birth

Summary Glycogen accumulation in the Clarke's nucleus neuropil of young adult rats whose sciatic nerves were crushed in the first postnatal day was investigated with the electron microscope. Glycogen was observed in synaptic boutons and in small myelinated axons. In some terminals, glycogen accumulated in membranebound structures resembling mitochondria and formed large multigranular bodies which were entirely separated from the axoplasm. The multigranular body reached the size of 1.3 m. Glycogen was present as single beta particles of about 25–40 nm in diameter and in aggregations of large alpha clusters. The astrocytic glycogen distribution was almost similar to that of the control specimens. Glycogen was not observed in other glial cells. It is probable that glycogen accumulation in synaptic terminals of partially deafferentiated Clarke's nucleus may result from impaired glycolysis due to deficient resupply of the distal axon with glycolytic enzymes caused by a defect in axoplasmic transport from the hypoplastic sensory neuronal perikarya.     

Meta-Analysis and Systematic Review of Micro- and Macro-Nutrient Intakes and Trajectories of Macro-Nutrient Supply in the Eastern Mediterranean Region

The Eastern Mediterranean Region (EMR) is experiencing a nutrition transition, characterized by the emergence of overnutrition and micro-nutrient deficiencies. No previous study has comparatively examined nutrient intake in adults across countries in the EMR. This review examined the adequacy of nutrients in adults living in the EMR. Moreover, it analyzed the food balance sheets (FBS) for 1961–2018 to identify the trajectory of energy supply from macro-nutrients in the EMR. A systematic search was conducted from January 2012 to September 2020. Only observational studies were retained with a random sampling design. An assessment of the methodological quality was conducted. Levels of nutrient daily intake and their adequacy compared to the daily reference intake of the Institute of Medicine were reported across the region. No studies were identified for half of the region’s countries. Although nutrient energy intake was satisfactory overall, fat and carbohydrate intake were high. Intake of vitamin D, calcium, potassium, zinc, and magnesium were below that recommended. The analysis of the FBS data allowed for the identification of four linear patterns of trajectories, with countries in the EMR best fitting the ‘high-energy-supply from carbohydrate’ group. This systematic review warrants multi-sectorial commitment to optimize nutrient intake.     

The Effect of Neonicotinoids Exposure on Oreochromis niloticus Histopathological Alterations and Genotoxicity

This study aimed to examine the side effects of selected neonicotinoids (Acetamiprid, Aceta, and Imidacloprid, Imid) on Oreochromis niloticus juveniles. The acute toxicity, Probit method, revealed an LC₅₀ of 195.81 and 150.76 ppm for Aceta/96 h and Imid/72 h respectively. The fish were divided into three groups that were exposed, for 21 days (n?=?5/replicate), to 1/10 of the LC₅₀ of either neonicotinoids, however, the third was an unexposed control group. Results of erythrocytic micronucleus (MN), and nuclear abnormalities (NA) showed that Aceta and Imid exposure caused a significant (p?<?0.05) increase in MN by?~?2.2 and?~?10 folds, respectively relative to control. NAs occurred at the order of kidney-shaped?>?budding?>?binucleated in Aceta, however, budding?>?binucleated?>?kidney-shaped was noticed in the Imid group. Histopathological changes in gills, liver, and muscles were observed significantly in both exposed groups with more severity in the Imid group. Collectively, Aceta and Imid have potential genotoxicity and histopathological alterations in O. niloticus.

     

Detubularized Isolated Ureterosigmoidostomy: Description of a New Technique and Preliminary Results

Purpose

A technique is described to improve the evacuation pattern and, accordingly, the life-style of patients with ureterosigmoidostomy.

Materials and Methods

An inverted U-shaped sigmoid colon is detubularized, and the left colon is fixed in continuity to the posterior wall of the rectal ampulla in line with the anorectal canal. The ureters are reimplanted into the sigmoid pouch using the nipple technique.

Results

All 15 patients followed for 3 to 18 months postoperatively passed clear urine and solid feces separately, with good anal control and at convenient periods (urine 3 to 6 times and solid feces once daily). Urographic studies showed stabilization of renal morphology in 26 units, improved function in 3 and deterioration in 1. Dynamic study of the rectum in 3 patients showed a capacious rectosigmoid reservoir with low pressure.

Conclusions

The technique of detubularized isolated ureterosigmoidostomy has important advantages over conventional ureterosigmoidostomy. Patients pass urine and feces separately and at convenient intervals with good anal control. The upper urinary tract is well preserved, and there is potentially less risk of colonic carcinogenesis.     

Loss of Fhit expression in head and neck squamous cell carcinoma and its potential clinical implication.

PURPOSE: Abnormalities of FHIT, a candidate tumor suppressor gene, have frequently been found in multiple malignancies, including head and neck squamous cell carcinoma (HNSCC). To define its role in HNSCC treated with surgery and postoperative radiotherapy (PORT), the Fhit protein expression status was investigated in 80 patients enrolled in a prospective Phase III clinical trial addressing the dose and fractionation regimen of PORT. EXPERIMENTAL DESIGN: Immunohistochemical staining of HNSCC tissue sections for Fhit expression was performed. The Fhit expression status was correlated with the clinicopathological characteristics and clinical course. The median follow-up duration was 4.9 years. RESULTS: Loss of Fhit expression was found in 52 of the 80 study patients (65%). There was not a significant association between Fhit expression and clinical characteristics. Patients whose tumor exhibited negative Fhit expression had a significantly worse 5-year overall survival duration [hazard ratio = 0.49; 95% confidence interval, 0.23-1.03; P = 0.05 (log-rank test)] than did those whose tumor exhibited positive Fhit expression. One third of the patients with a Fhit-negative tumor had distant metastasis during the follow-up period. Paradoxically, patients classified as high risk who had a Fhit-negative tumor experienced locoregional recurrence less often (18%) than did high-risk patients who had a Fhit-positive tumor (33%). CONCLUSIONS: Loss of Fhit expression is a poor prognostic indicator in patients with HNSCC. However, tumors lacking Fhit expression may be more sensitive to PORT and therefore more susceptible to locoregional control.     

p53 mutations in human aggressive and nonaggressive basal and squamous cell carcinomas.

PURPOSE: The purpose is to investigate whether aggressive basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) differ from nonaggressive BCC and SCC with respect to the p53 mutation spectrum and whether specific mutations can serve as prognostic indicators of tumor aggressiveness. EXPERIMENTAL DESIGN: We analyzed 342 tissues from patients with aggressive and nonaggressive BCCs and SCCs for p53 mutations by single-strand conformation polymorphism and nucleotide sequencing. RESULTS: p53 mutations were detected in 33 of 50 aggressive BCCs (66%), 37 of 98 nonaggressive BCCs (38%), 28 of 80 aggressive SCCs (35%), 28 of 56 nonaggressive SCCs (50%), and 3 of 29 samples of sun-exposed skin (10%). About 71% of the p53 mutations detected in aggressive and nonaggressive BCCs and SCCs were UV signature mutations. The frequency of CC to TT mutations in aggressive (36%) and nonaggressive SCCs (39%) was 2-fold higher than in aggressive (18%) and nonaggressive (14%) BCCs. In contrast, aggressive BCCs had a higher frequency (24%) of transversions than nonaggressive BCCs (8%) and aggressive (14%) and nonaggressive (11%) SCCs did. CONCLUSIONS: Our results indicate that UV radiation is responsible for the induction of p53 mutations and perhaps for the initiation of both aggressive and nonaggressive BCCs and SCCs. Although some differences in p53 mutation frequency, types of mutation, and hot spots were seen between aggressive and nonaggressive BCCs and SCCs, these factors do not constitute as clear-cut diagnostic or prognostic indicators of tumor aggressiveness. Tumor aggressiveness may be attributable to other genetic changes or events that occur during tumor progression.     

Confocal microscopy for real-time detection of oral cavity neoplasia.

PURPOSE: The goal of this study was to characterize features of normal and neoplastic oral mucosa using reflectance confocal microscopy. EXPERIMENTAL DESIGN: Oral cavity biopsies were acquired from 17 patients at the Head and Neck Clinic of The University of Texas M. D. Anderson Cancer Center who were undergoing surgery for squamous cell carcinoma within the oral cavity. Reflectance confocal images were obtained at multiple image plane depths from biopsies within 6 h of excision. After imaging, biopsies were fixed in 10% formalin and submitted for routine histological examination. Reflectance confocal images were compared with histological images from the same sample to determine which tissue features contribute to image contrast and can be potentially imaged using in vivo confocal microscopy. RESULTS: Confocal images were successfully acquired from 15 biopsy pairs from 17 patients. Depth-related changes in cell diameter and nuclear density were observed at multiple anatomical sites within the oral cavity. In squamous cell carcinomas, densely packed, pleomorphic tumor nuclei could be visualized with distinct differences in nuclear density and morphology distinguishable between confocal images of neoplastic and nonneoplastic oral cavity. Other features of noncancerous and cancerous oral tissue that could be identified in the confocal images included areas of inflammation, fibrosis, muscle fibers, and salivary glands. CONCLUSIONS: Our results support the potential for this tool to play a significant role in the clinical evaluation of oral lesions, real-time identification of tumor margins, and monitoring of response to therapeutic treatment.     

Primary percutaneous approach to upper urinary tract transitional cell carcinoma

The optimal approach to upper tract TCC remains to be redefined. A routine nephroureterectomy for every filling defect in the upper urinary system, even in the case of a normal contralateral kidney, constitutes an unnecessary mutilation in more than two thirds of the cases. Nephroureterectomy does not reduce the need for a long-term cystoscopic follow-up because of the high rate of bladder tumor recurrence that may happen years later after nephroureterectomy. Relying solely on radiography and cytology, lacking sensitivity and specificity, to recommend a nephroureterectomy is against the principles of oncologic surgery, especially now that preoperative histologic proof is easy to obtain endoscopically without compromising cancer control. Ureteroscopy, rigid and flexible, provides a complete assessment of the upper urinary system. Biopsy specimens taken with ureteroscopy may be sufficient for grading but less adequate for staging of the tumor. The authors reserve ureteroscopy for ureteral tumors and small (< 1.5 cm) single tumors of the renal pelvis. They approach large or multiple tumors of the renal pelvis percutaneously, in which a full histologic assessment is possible along with a complete resection of the tumor. The decision on the therapeutic approach is made only after the final pathologic report is reviewed. Grade I and grade II superficial disease (Ta, T1) can be treated endoscopically with minimal morbidity and with an efficiency comparable with the standard more invasive nephroureterectomy (Table 5). The indications for endourologic treatment in these cases can be extended safely beyond a solitary kidney or a high surgical risk to include any healthy individual with a normal contralateral kidney who is willing to commit to a rigorous lifelong follow-up. Patients with grade II T1 lesions require a more vigilant follow-up. For grade III Ta disease, more caution should be exercised in selecting these patients for elective endourologic management. When criteria of good prognosis are found, such as absence of carcinoma in situ, presence of diploidy, low p53 expression and a single-tumor, endoscopic management can be offered [table: see text] with a closer follow-up and resorting always to immediate nephroureterectomy at the first evidence of upstaging. Because of the high incidence of recurrence and progression, elective endourologic management for grade III T1 tumors is not recommended. Endoscopic conservative surgery still can be offered in the cases of a solitary kidney or chronic renal insufficiency or for poor surgical candidates. Patients with localized stages (T2, T3) TCC should be offered immediate nephroureterectomy. The authors do not expect adequate endoscopic extirpation with muscle invasive tumors. Although the tissue removed may include deep layers, deep resection is precluded by the thin renal pelvic wall and the associated risk for perforation. Patients with more extensive disease (T3, T4) have a bad prognosis regardless of the form of therapy. Achieving local control percutaneously while preserving as many nephrons as possible for the future chemotherapy can be a reasonable option.