Rejected

Symptomatic pleural effusion is occasionally caused by superior vena cava syndrome. Dyspnea and pleuritic chest pain are common symptoms of pleural effusion. However, the current literature has not reported a causal linkage between chylous pleural effusion and dry cough.

Non-invasive Gamma ENtrainment Using Sensory stimulation (GENUS) at 40Hz reduces Alzheimer's disease (AD) pathology such as amyloid and tau levels, prevents cerebral atrophy, and improves behavioral testing performance in mouse models of AD. Here, we report data from (1) a Phase 1 feasibility study (NCT04042922, ClinicalTrials.gov) in cognitively normal volunteers (n = 25), patients with mild AD dementia (n = 16), and patients with epilepsy who underwent intracranial electrode monitoring (n = 2) to assess safety and feasibility of a single brief GENUS session to induce entrainment and (2) a single-blinded, randomized, placebo-controlled Phase 2A pilot study (NCT04055376) in patients with mild probable AD dementia (n = 15) to assess safety, compliance, entrainment, and exploratory clinical outcomes after chronic daily 40Hz sensory stimulation for 3 months. Our Phase 1 study showed that 40Hz GENUS was safe and effectively induced entrainment in both cortical regions and other cortical and subcortical structures such as the hippocampus, amygdala, insula, and gyrus rectus. Our Phase 2A study demonstrated that chronic daily 40Hz light and sound GENUS was well-tolerated and that compliance was equally high in both the control and active groups, with participants equally inaccurate in guessing their group assignments prior to unblinding. Electroencephalography recordings show that our 40Hz GENUS device safely and effectively induced 40Hz entrainment in participants with mild AD dementia. After 3 months of daily stimulation, the group receiving 40Hz stimulation showed (i) lesser ventricular dilation and hippocampal atrophy, (ii) increased functional connectivity in the default mode network as well as with the medial visual network, (iii) better performance on the face-name association delayed recall test, and (iv) improved measures of daily activity rhythmicity compared to the control group. These results support further evaluation of GENUS in a pivotal clinical trial to evaluate its potential as a novel disease-modifying therapeutic for patients with AD.

It is known that exercise can be one of the causes of muscular damage. In recent times, physiotherapists and medical professionals have been employing USGET techniques to stimulate muscle recovery to improve its performance after the injury. We pretend to analyse if the Ultrasound-guided electrolysis (USGET) technique could reduce muscle damage, inflammation, and pain in the present study. Female Wistar rats were assigned to one of three different groups: control (C), notexin (NOT) and notexin with USGET (electrolysis at 6mA) (NOT+USGET). We used the USGT technique, based on electrical stimulation with a continuous current of 4 pulses at an intensity of 6 mA for 5 seconds, conveyed to the muscle. The response was tested with motor function tests. In these tests, we could observe an increase in time and foot faults when crossing a beam in the NOT group compared to C group rats. On the other hand, a significant decrease in both variables was detected in the NOT+USGET compared to the NOT group. Muscle power was measured with a grip strength test, obtaining far better performances in NOT+USGET rats when compared to NOT rats. Moreover, the USGET technique prevented the increase of pro-inflammatory proteins IL-6 and chemokines CCL3 (Chemokine (C-C motif) ligand 3), CCL4 (Chemokine (C-C motif) ligand 4), and CCL5 (Chemokine (C-C motif) ligand 5) with their receptor CCR5 (C-C chemokine receptor type 5), induced by notexin in the quadriceps. At the same time, the study evidenced a decrease in both CCR8 (C-C chemokine receptor type 5,) and NF-ᴋB (nuclear factor- ᴋB) expressions after USGET treatment. On the other hand, we obtained evidence that demonstrated anti-inflammatory properties of the USGET technique, thus being the increase in IL-10 (Interleukin 10) and IL-13 (Interleukin 13) in the NOT+USGET group compared to the NOT group. Furthermore, when applying NSGET after damage, an increase in anti-inflammatory mediators and reduction of pro-inflammatory mediators, which, overall, promoted muscle regeneration, was observed. These results support the idea that the NSGET technique improves muscle recovery after toxic damages, which would justify its employment.

CD47-SIRPα interaction acts as a "don't eat me" signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). Of these, 6.4% experienced complete response, 10.4% partial response, and 26.1% stable disease for a 16.7% objective response rate (ORR), 42.8% disease control rate, and 4.8-month median duration of response. ORR was significantly higher for hematologic cancers (25.3%) than solid cancers (9.1%, p=0.042). Comparing by mechanism, seven CD47 monoclonal antibodies (mAbs) and six selective SIRPα blockers were given alone or combined with checkpoint inhibitors, targeted therapy, and/or chemotherapy. In solid cancers, selective SIRPα blockade showed a higher ORR (16.2%) than anti-CD47 mAbs (2.8%, p=0.079), which was significant for combination therapies (ORR 28.3% vs 3.0%, respectively, p=0.010). Responses were seen in head and neck, colorectal, endometrial, ovarian, hepatocellular, non-small cell lung, and HER2+gastroesophageal cancers. Dose-limiting toxicity (DLT) was seen in 3.3% of patients (5.4% anti-CD47 mAbs, 1.4% selective SIRPα blockers; p=0.01). The frequency of treatment-related adverse events (TRAEs) ≥grade 3 was 18.0%, similar between the two groups (p=0.082), and mostly laboratory abnormalities. For anti-CD47 mAbs, the most common toxicities included grade 1-2 fatigue (27.2%), headache (21.0%), and anemia (20.5%). For selective SIRPα blockers, these included grade 1-2 infusion reaction (23.1%) and fatigue (15.8%). Anti-CD47 mAbs were significantly more likely than selective SIRPα blockers to cause grade 1-2 fever, chills, nausea/vomiting, headache, and anemia. In conclusion, combination therapies using selective SIRPα blockade had higher response rates in solid tumors than anti-CD47 mAb combinations. Hematologic changes were the main TRAEs, and selective SIRPα blockers seemed to have a better grade 1-2 toxicity profile. Treatment was well-tolerated with minimal DLTs.

Pain management after surgery is a challenging medical issue, and clinical research in this area has continued. This study aimed to compare the effect of Aminophylline, ketamine, and paracetamol on the pain intensity after deep vitrectomy and compare it with the control group.

Migraine plays an important role in some subgroups of children with recurrent vertigo. Moreover, the migraine component varies from definite to possibly absent as defined in this spectrum of three disorders-vestibular migraine of childhood (VMC), probable VMC (pVMC), and recurrent vertigo of childhood (RVC). However, studies on the sensory organization of balance control in these three disorders are rare.

Connective tissue disorders such as Ehlers-Danlos Syndrome (EDS) can affect collagen and elastin content and structure, including weakening of tissues and vasculature, thus contributing to multiple systemic manifestations. Prior research has successfully focused on peripheral life-threatening manifestations resulting in increased life expectancy, yet clinical observations have warranted investigation of neurological vulnerability, where little is known. Compromised brain tissues and cerebrovasculature could leave these patients vulnerable to mild traumatic brain injury (TBI), with increased severity and duration of post-concussive symptoms and delayed recovery. Clinical reports in adults indicate that higher severity of symptoms after a mild TBI, such as a concussion, can unmask connective tissues disorders leading toward diagnosis. This clinical case report is an example of a pediatric patient with presumed Ehlers-Danlos syndrome who demonstrates increased vulnerability to mild TBI/concussion.

Bromelain is a key enzyme found in pineapple (.); a proteolytic substance with multiple beneficial effects for human health such as anti-inflammatory, immunomodulatory, antioxidant and anticarcinogenic, traditionally used in many countries for its potential therapeutic value. The aim of this updated and comprehensive review focuses on the potential anticancer benefits of bromelain, analyzing the cytotoxic, apoptotic, necrotic, autophagic, immunomodulating, and anti-inflammatory effects in cancer cells and animal models. Detailed information about Bromelain and its anticancer effects at the cellular, molecular and signaling levels were collected from online databases such as PubMed/MedLine, TRIP database, GeenMedical, Scopus, Web of Science and Google Scholar. The results of the analyzed studies showed that Bromelain possesses corroborated pharmacological activities, such as anticancer, anti-edema, anti-inflammatory, anti-microbial, anti-coagulant, anti-osteoarthritis, anti-trauma pain, anti-diarrhea, wound repair. Nonetheless, bromelain clinical studies are scarce and still more research is needed to validate the scientific value of this enzyme in human cancer diseases.

Intestinal neuronal dysplasia (IND) is a rare condition mainly affecting the children. Constipation and abdominal distension have been reported as common manifestations. In addition, the reports about adult cases are scarce.

Cerebral venous thrombosis (CVT) is a rare disease that frequently occurs in young women of childbearing age, with variable clinical presentation in regions with limited access to diagnostic imaging or specialized neurological care. In the last decade, there has been an increase in the number of studies on CVT in Latin America, which may contribute to a better epidemiological description of the disease in this region and, consequently, its early diagnosis.