Functional Analysis of Spike from SARS-CoV-2 Variants Reveals the Role of Distinct Mutations in Neutralization Potential and Viral Infectivity

Enhanced viral transmission and escape from vaccine–elicited neutralizing antibodies drive worldwide spread of SARS-CoV-2 variants and promote disease progression. However, the impact of specific spike mutations that are carried by different viral variants on viral infectivity and neutralization sensitivity has not been completely defined. Here, we use pseudoviruses to assess the contribution of spike mutations within the Receptor Binding Domain (RBD) and the Furin Cleavage Site (FCS), and appear in circulating viral variants, on viral infectivity and neutralization potential against sera that was drawn from fully vaccinated individuals. Our functional analysis demonstrates that single, P681H, P681R or A701V–FCS mutations do not play a role in viral infectivity and neutralization potential. However, when in conjunction with the RBD–N501Y mutation, viral infectivity is enhanced. Similarly, combining the E484K–RBD mutation to the spike that carries FCS mutations reduces neutralization sensitivity with no effects on viral infectivity. Employing a similar approach onto the spike from Delta or Lota SARS-CoV-2 variants further reveals that specific RBD mutations affect neutralization sensitivity or viral infectivity differently. Our results validate the efficacy of the Pfizer third dose vaccine against Delta and Lota SARS-CoV-2 variants, and outline the significance of distinct RBD mutations in promoting viral infectivity and neutralization sensitivity to post–vaccination sera.     

Endometrioid carcinoma of the oviduct

Endometrioid carcinoma is a malignant tumor which microscopically resembles endometrial adenocarcinoma, but arises from extrauterine sites, most commonly the ovary. Although its association with endometriosis has received considerable discussion, it appears that most of the malignant endometrioid tumors arise de novo. We present a case of endometrioid carcinoma which is outstanding for its primary site in the oviduct and for its histologic appearance, which incorporated a close interplay between both stromal and epithelial elements. The neoplasm was found incidentally, when the woman presented with postmenopausal bleeding due to adenomatous hyperplasia of the endometrium. The patient presented with a stage I, grade I tumor which did not invade the wall of the oviduct. Twelve years following a TAH-BSO and postoperative radiation, the tumor recurred, requiring additional surgery and chemotherapy. The patient is currently disease free, 2 years from her recurrence.     

Dexmedetomidine in intensive care unit: a study of hemodynamic changes

BACKGROUND: Dexmedetomidine is a potent new alpha-2 adrenoceptor agonist with an alpha-2 to alpha- ratio more than 7 times that of clonidine. Its potent sedative, analgesic and sympatholytic effects blunt the cardiovascular responses (hypertension, tachycardia) without unexpected toxicity. Many reports confirmed its pharmacological properties if given by infusion. Recent report confirmed favorable non-depressant effect on respiration and blood gases. SETTING: ICU patients at King Khalid University Hospital. PATIENTS AND METHOD: Open label clinical evaluation on ten surgical patient ASA I class received dexmeditomidine infusion to the sedative effect level of Ramsy scale of 3 for ventilated patients and 2 for spontaneously breathing patient. The clinical observation and analgesic requirement as well as the hemodynamic parameters and hemoglobin oxygen saturation were observed for the period of ventilation and weaning till discharge from the ICU. These records were subjected to paired t test for values measured at preinfusion period compared to 10 minutes and 6 hours measurement after infusion. RESULTS: The study confirmed the previous findings of previous reports regarding the cardiovascular stability and non depressive effect on respiration. It also confirmed the sparing effect on the use of analgesics which indicates its analgesic effect. The sedation quality is unique in that the patient is easily arousable. This was reported favorably by the nursing staff. Bradycardia was observed in one patient who was treated effectively by stopping the infusion. CONCLUSION: We concluded that dexmedetomidine is useful sedative agent with analgesic properties which reduce the analgesic requirement of the patient. The patient were ventilated, weaned, then breathed spontaneously in a satisfactory manner.     

RhoGDI2 is an invasion and metastasis suppressor gene in human cancer

To discover novel metastasis suppressor genes that are clinically relevant in common human cancers, we used isogenic human bladder cancer cell lines and used DNA microarray technology to identify genes whose expression diminishes as a function of invasive and metastatic competence. We then evaluated the expression profile of such genes in 105 pathologically characterized tumors from seven common organ sites, and we identified one gene, RhoGDI2, whose expression was diminished as a function of primary tumor stage and grade. When RhoGDI2 was transferred back into cells with metastatic ability that lacked its expression, it suppressed experimental lung metastasis but did not affect in vitro growth, colony formation, or in vivo tumorigenicity. In addition, RhoGDI2 reconstitution in these cells blocked invasion in an organotypic assay and led to a reduction of in vitro motility. These results indicate that RhoGDI2 is a metastasis suppressor gene, a marker of aggressive human cancer, and a promising target for therapy.     

ACTH-secreting islet cell tumor of the pancreas presenting as bilateral ovarian tumors and Cushing's syndrome.

A 41-year-old woman presented with hirsutism, a pelvic mass, and Cushing's syndrome. Imaging studies revealed bilateral ovarian masses and a solid and cystic mass within the pancreas. Partial pancreatectomy, bilateral oophorectomy, and excision of several peritoneal tumor nodules were performed. Pathological examination revealed a neuroendocrine islet cell tumor of the pancreas with bilateral ovarian metastases. The tumor was immunoreactive for ACTH, chromogranin, neuron-specific enolase, and keratin. The patient received postoperative chemotherapy and has been disease-free for 6 years. To our knowledge, this is the first reported case of an ACTH-secreting pancreatic neuroendocrine tumor presenting as bilateral ovarian metastases.