Month: September 2023

In a recent study published in the journal Science Translational Medicine, researchers investigate the potential of mitochondrial deoxyribonucleic acid (mtDNA) injury as a serological marker for Parkinson’s disease (PD) using the novel Mito DNADX test. Study: A blood-based marker of mitochondrial DNA damage in Parkinson’s disease. Image Credit: Kateryna Kon / Shutterstock.com What causes PD? PD is a neurodegenerative movement disorder with progressive loss of dopaminergic neurons that causes tremors, rigidity, bradykinesia, and postural instability. High-throughput markers are needed to stratify PD patients and ensure the success of disease-modifying therapies. Mitochondrial dysfunction plays a significant role in PD pathogenesis, with mtDNA damage observed in PD neuronal cultures and animal models. The development of blood-based molecular markers could transform clinical trials and enhance the success of disease-modifying therapies. About the study In the present study, researchers investigate whether the polymerase chain reaction (PCR)-based DNADX assay could enable accurate quantification of mtDNA damage in real-time. The DNADX assay, which utilizes the deoxyribonucleic acid polymerase enzyme and fluorescent dyes, was used to quantify mtDNA damage in patients with idiopathic PD. The assay involved amplification of PCR fragments targeting the mitochondrial genome, which increases mtDNA injury as compared to controls. The count of mtDNA lesions depended on the hydrogen peroxide (H2O2) concentration. Agarose gel electrophoresis was performed to verify the appropriate size of mitochondrial amplicons. Related Stories A semi-automated DNA extraction workflow was used to isolate six specimens within 12 minutes to optimize analytical variables for developing biomarkers and enhancing throughput. The DNADX assay results were also compared to those obtained from traditional assays used to quantify DNA injury using enriched mtDNA samples retrieved from H2O2-treated human embryonic kidney 293 (HEK293) cells. The effects of leucine-rich repeat kinase 2 (LRRK2) inhibitors on mtDNA injury were also assessed in cells isolated from the blood of idiopathic PD patients. To address the potential confounding role of PD-related drugs in studies of mtDNA damage, blood and clinical data were gathered from an independent cohort of people with PD during a washout period. The team investigated whether increases in peripheral mtDNA injury were observed among LRRK2-G2019S mutational carriers with or without a PD diagnosis and compared them with an independent group of idiopathic PD patients. To examine whether mtDNA damage could also be used as a marker for other neurodegenerative diseases, samples obtained from patients with Alzheimer’s disease (AD) were also studied, in addition to age-matched and healthy control individuals recruited from the Memory Disorders Clinic at Duke University. Study findings Increased mtDNA damage was observed in PMBCs obtained for idiopathic PD-type patients and those comprising the PD-related LRRK2 amino acid substitution as compared with similarly aged controls. This damage could occur regardless of a PD diagnosis. Compared to controls, LRRK2 G2019S mutation knock-in murine animals exhibited more mtDNA damage. However, LRRK2 knockout murine animals exhibited fewer mtDNA lesions within the ventral area of the midbrain. In the PD murine midbrain neuronal model and idiopathic PD patient-derived cells, a small-molecule-type LRRK2 inhibitor reduced mtDNA damage. The mtDNA damage observed in cells derived from individuals with idiopathic PD was mitigated with LRRK2 kinase inhibition. MLi-2, a high dosage of the LRRK2 kinase inhibitor, repaired mitochondrial damage to the control baseline in idiopathic PD patient-derived LCLs within 24 hours, with no change in mtDNA copy number. The pathogenic kinase-activating G2019S amino acid substitution impaired basal mitophagy, whereas LRRK2 deficiency enhanced basal mitophagy. PD patients exhibited elevated amounts of mtDNA damage with or without washout. Increased mtDNA damage was observed among individuals carrying the LRRK2 mutation. Longitudinal mtDNA lesion frequency was stable in healthy controls, thus indicating that loss of mtDNA maintenance is associated with the disease process rather than due to preanalytical factors associated with sample collection, DNA extraction, or the DNADX assay. Conclusions LRRK2 contributes to mitochondrial gene homeostasis; therefore, LRRK2 mutation carriers have higher levels of mtDNA damage. In healthy controls, the incidence of mitochondrial DNA lesions remained steady throughout the period, whereas blood-derived cells from individuals with idiopathic PD exhibited increased mtDNA damage. The DNADX assay for assessing mtDNA damage may be a valuable technique for diagnosing PD and measuring the pharmacodynamic response to LRRK2 kinase inhibitors. Moreover, LRRK2 kinase inhibition reduced mtDNA damage in cells obtained from patients with idiopathic PD. Journal reference: Qi, R., Sammler, E., Gonzalez-Hunt, C. P., et al. (2023). A blood-based marker of mitochondrial DNA damage in Parkinson’s disease. Science Translational Medicine 15. doi:10.1126/scitranslmed.abo1557

BIRMINGHAM, Ala. (WBRC) – It’s Alabama Blood Donation Day and the American Red Cross says they’re at a 2-3 day supply of blood, but ideally they want a 4-5 day supply. Leaders say that blood donations tend to drop during the summer months, and they hope to see more people come out and donate as it gets closer to fall. Annette Rowland with the American Red Cross says statistically, only 3% of the U.S. population donates blood. Unfortunately, only some people in that 3% are actually eligible to give. Because the need for blood can be a life or death situation, Governor Kay Ivey joined other governors across the country in declaring a state Blood Donation Day. In the proclamation, the governor says she hopes it reminds people that we need to replenish our blood supply in Alabama. “It’s a matter of life and death but it’s also thinking, ‘I don’t want my family member or myself to have to go through a situation where I need blood and it’s not there,’” said Rowland. “And the only way we can prevent that from happening is by donating blood.” Rowland says the number one reason people haven’t donated blood before is because they simply haven’t been asked. She is asking people to donate if they are able because it could save someone’s life. You can schedule an appointment to give blood by clicking here. Get news alerts in the Apple App Store and Google Play Store or subscribe to our email newsletter here. Copyright 2023 WBRC. All rights reserved.

<!– –> She was then taken to a hospital in Lucknow where her condition is believed to be stable. Lucknow: The Allahabad High Court on Sunday pulled up both the Uttar Pradesh government and the railway police over the attack on a woman constable who was found in a “pool of blood” inside a train compartment on August 30. Chief Justice Pritinker Diwaker convened a late evening hearing at his residence on Sunday along with Justice Ashutosh Srivastava based on a WhatsApp message he received about the case. The two-judge bench slammed the Railway Protection Force (RPF) for “failing in discharge of its duties” and ordered the Government Railway Police (GRP) to submit a status update on its investigation into the case by September 13. According to the GRP, the woman constable was found in a “pool of blood” with injuries to her face and head in a Saryu Express compartment on August 30. She was then taken to a hospital in Lucknow where her condition is believed to be stable. An FIR was lodged by the woman’s brother on the same day, the police said. The police and the family of the woman have both denied any sexual assault angle to the case. The court also issued notices to the Centre, the Ministry of Railways, the director general of RPF, the Uttar Pradesh government, and the Ministry of Home and State Commission for Women. “The 47-year-old woman head constable, who hails from the Prayagraj district, was posted in Sultanpur district,” Puja Yadav, the officer in charge of the investigation had said after the incident. “She was coming from Sultanpur to Ayodhya on ‘Saavan Mela’ duty. She was supposed to deboard at Ayodhya, but reached a railway station called Manakpur as she had slept in the train. The incident took place between Ayodhya and Mankapur.” Senior officials of the UP Police visited the injured woman constable at the King George’s Medical University (KGMU) in Lucknow. The police are yet to solve the case and have been unable to determine the motive behind the brutal attack on the woman.

Researchers have found that red blood cells have an innate ability to trigger a pathway that protects the heart from injury during periods of low oxygen, such as during a heart attack. The effect was stronger in people fed a diet high in nitrates, found in green leafy vegetables like spinach and arugula. Red blood cells (RBCs) carry oxygen from the lungs to the rest of the body, returning carbon dioxide to the lungs where it’s expelled. However, some studies have suggested that in addition to their role as oxygen carriers, RBCs can sense hypoxia, or low oxygen levels, and respond by producing a signal that causes the release of nitric oxide (NO), which causes vasodilation or widening of the blood vessels. NO is a naturally produced vasodilator. It’s thought, somewhat controversially, that its actions produce an effect that protects the heart against injury during hypoxia. Now, researchers from the Karolinska Institutet in Sweden have investigated the RBC signaling pathway to determine whether the cells have an innate ability to induce cardioprotection when oxygen levels are low. First, the researchers looked at whether RBCs exposed to hypoxia released a cardioprotective mediator. Introducing RBCs from mice exposed to normal and low oxygen levels to mouse myocardial infarction (heart attack) models, they found that the hypoxic RBCs significantly improved heart function and reduced the size of tissue damage caused by low oxygen levels compared to RBCs exposed to normal oxygen levels. Having determined that a cardioprotective factor was released from RBCs during hypoxia, the researchers set about determining the nature of this compound. They knew that RBCs carry soluble guanylate cyclase (sGC), which forms guanosine 3’,5’-cyclic monophosphate (cyclic GMP or cGMP), a messenger molecule that modulates many bodily pathways, including vasodilation. So, to determine the involvement of sGC, they exposed RBCs taken from mice that’d been genetically modified not to produce sGC to hypoxia and administered them to myocardial infarction models. The RBCs failed to protect the hearts against injury. The next step was to determine if cGMP, the product of sGC, was exported from the RBCs and its role in the cardioprotective effect produced by hypoxic RBCs. Phosphodiesterase 5 (PDE5), a cGMP inhibitor, was administered to the hypoxic RBCs before they were introduced to the heart model. The researchers found that the introduction of PDE5 abolished the cardioprotective effect. Since they’d confirmed that the sGC-cGMP pathway played a role in RBC-induced cardioprotection, the researchers looked at NO’s role in the pathway. In the body, inorganic nitrate can be reduced to nitrite and further reduced by deoxygenated hemoglobin to NO. So, they put inorganic nitrate in the mice’s drinking water for four weeks, after which they collected RBCs and administered them to the heart models. Hearts receiving hypoxic RBCs from nitrate-treated mice showed significantly better recovery and smaller tissue damage size than those from control mice. The researchers found that the cardioprotective effect of nitrate and hypoxia was greater than that of hypoxia alone. To translate the beneficial effect of adding nitrate in mice to the clinical situation, the researchers collected RBCs from three groups of human subjects who’d been randomized to a five-week dietary intervention: two groups with high nitrate intake in the form of a potassium nitrate tablet or nitrate-rich vegetables, and one group receiving a low dietary intake of nitrate. These RBCs were then administered to rat heart models subjected to hypoxia. RBCs from both high-nitrate groups significantly improved cardiac recovery compared with those from the low-nitrate group. “The results show both that the red blood cells convey protection against injury in the heart in the event of low oxygen levels, and how that protection can be enhanced through simple dietary advice,” said Jiangning Yang, the study’s lead author. “This may be of great importance for patients at risk of myocardial infarction.” The researchers plan to develop drugs that activate the RBC’s protective signaling mechanism during hypoxia. “In addition, we need to map how the blood cells transmit their protective signal to the heart muscle cells,” said John Pernow, a corresponding author of the study. The study was published in the Journal of Clinical Investigation. Source: Karolinska Institutet

UPPER PENINSULA, Mich. (WJMN) – On this Aspirus Medical Monday, a new outpatient therapy that is now being offered at Aspirus Health is being highlighted. It’s called blood flow restriction training, also known as BFR, which helps individuals recover from an injury or surgery. Aspirus Physical Therapists (and brothers) Blake and Beau Dupuis recently obtained their certification to offer this unique service. This certification allows Blake and Beau to intentionally apply blow flow restriction to maximally enhance rehabilitation of musculoskeletal conditions and enhance performances of athletes. “The blood flow restriction training is basically a way for us to train with really lightweights and adapt like we’re using really heavy weights,” said Physical Therapist Blake Dupuis at Aspirus Health. “So basically, you put a fancy blood pressure cuff on your upper extremity or your lower extremity, and it’s going to restrict some of the blood flow, not all of it to the target muscle that we’re going after. And this sort of tricks your extremity that is working very hard in and can actually promote the same of muscular gains and strength. And then if we were going to be using really, really heavy weights, and it’s good for people who can’t tolerate heavy weights, so they got bad pain and they can’t, can’t tolerate lifting really heavy weights. We strap this blood pressure cuff around their leg or their arm that can use lighter weights and still adapt to that exercise. Like they’re using heavy weights.” Blood Flow Restriction Training can be used to help patients with a variety of injuries including: Tennis Elbow Rotator Cuff injuries ACL and UCL injuries Ankle injuries Arthritis Hip injuries Thigh and hamstring injuries “BFR is a great tool for athletes or individuals who have a specific injury like a tear in their ACL, meniscus, sprains and strains,” said Beau Dupuis, DPT, Physical Therapist. “During recovery from an injury or surgery, patients can face loss of muscle tissue. BFR uses low intensity resistance and places less stress on the injured area. This allows for the individual to start earlier rehabilitation and help prevent loss of muscle mass.” BFR is also used to treat tendonitis, to provide general strengthening, and to help recover after surgery. Aspirus Health currently offers free 15-minute consultations with any physical, occupational or speech therapist. Consultations allow individuals to have an area or problem examined and to discuss whether therapy may be beneficial. Visit aspirus.org for more information on outpatient therapy. To schedule a consultation or appointment at Aspirus Outpatient Therapies in Calumet or Houghton, call 906-337-7000.

FRESNO, Calif. (KFSN) — After tragedy struck a northwest Fresno family two years ago, three sisters are taking action to honor their late mother while helping the community. “My mom would still be here today if she was able to get transfused quick enough,” said Jaycee Bear. Her mother, Cynde LeBlanc, passed away unexpectedly two years ago because she could not get a blood transfusion. Now, Jaycee and her sisters, Kaylee and Lacey Bear, are taking action. They have organized a blood drive in Cynde’s name for the second year. “One little pinch, you’re done,” Jaycee Bear said. “You’re here about 10-15 minutes, and then you can save up to three lives.” She and her sisters are encouraging Valley residents to donate blood at the Central California Blood Center by September 15th. Donors will even get something in return. “Me and my sisters are giving out services for each of our businesses if you donate,” Jaycee Bear said. Kaylee will give you half off an eyelash or eyebrow service, Jaycee will give you half off a pedicure or full set, or you can get $50 toward sweets at Lacey’s bakery while supplies last. All you need to do is donate by the 15th under Leblanc’s name. The blood drive could not come at a better time. “Coming off a three-day weekend, we tend to see an increased need for blood,” said Tamar Karkazian, the Donor Engagement and Community Development Manager at the Central California Blood Center. “So, the timing of the blood drive is really crucial and helpful,” Karkazian said. “It’s a great time to find the time to donate.” Most people over 16 can donate in less than an hour, and Karkazian says your donation will hit hospital shelves here in Fresno within 72 hours. The Bears say it is a great way to honor their late mom while helping others. “She was such a good person,” Jaycee Bear said of her mother. “She was so sweet. She loved her family. She loved her kids. I know she’s so happy that me and my sisters have been able to give back to the community.” The three sisters plan to donate blood together as a family on September 8th, the second anniversary of their mother’s passing. For news updates, follow Gabe Ferris on Facebook, Twitter and Instagram.

REGINA – The Winnipeg Blue Bombers, despite a slow start and varying degrees of ineffectiveness in all three phases the rest of the way, still had a chance to beat their biggest rivals on the most exciting weekend in the CFL regular season. But taking a four-point lead – their first in the game – late in the fourth quarter proved too thin a cushion against the Saskatchewan Roughriders, who answered back to claim a thrilling and controversial 32-30 overtime victory in the 58th edition of the Labour Day Classic at Mosaic Stadium Sunday. The Bombers trailed 3-0 after the first quarter, were down 13-7 at halftime and were behind 19-14 through three quarters when an idiotic and dangerous play by Roughriders defensive lineman Pete Robertson turned the game completely on its head. Robertson inexplicably headbutted Bombers quarterback Zach Collaros, who was forced from the game for a brief time by the league’s concussion spotter, giving the Bombers a new set of downs near the goal line and leading to the go-ahead touchdown by running back Brady Oliveira. <img src="https://medicalguru.us/wp-content/uploads/2023/09/1669545_web1_CP168173517.jpg" alt=" HEYWOOD YU / THE CANADIAN PRESS Winnipeg Blue Bombers receiver Drew Wolitarsky (82) catches for a touchdown as Saskatchewan Roughriders defensive back Nic Marshall (3) looks on during the first half of CFL Labour Day Classic football action in Regina, Sunday. “> HEYWOOD YU / THE CANADIAN PRESS Winnipeg Blue Bombers receiver Drew Wolitarsky (82) catches for a touchdown as Saskatchewan Roughriders defensive back Nic Marshall (3) looks on during the first half of CFL Labour Day Classic football action in Regina, Sunday. But slowly and surely the Roughriders chipped away at the Bombers lead, earning one point on a rouge before Brett Lauther kicked an 18-yard field goal with less than a minute remaining to send the game to extra time. From there, Saskatchewan struck first, with Antonio Pipkin punching in a one-yard TD and Shawn Bane Jr. converting the ensuing two-point covert, which proved to be the deciding points after Collaros found Kenny Lawler for a 35-yard score on Winnipeg’s first play of OT, only to have his pass tipped at the line of scrimmage on the game-tying convert attempt. Tempers flared afterwards, with team president and CEO Wade Miller, head coach Mike O’Shea and Collaros all still fuming from Robertson’s helmet-to-helmet attack. This one had plenty of juice to it, and that bad blood is surely to seep into this week’s rematch in the annual Banjo Bowl at IG Field Saturday afternoon. But before we peek too far ahead, let’s take a look back at Sunday’s game in the latest edition of 5 Takeaways. 1) Collaros was absolutely livid when he came out to speak to reporters. He spoke for 79 seconds, lamenting the slow start and up-and-down performance of his offence, but what he clearly wanted to talk about was the Robertson hit. Collaros, who has a history of head injuries over his football career, when asked by the Free Press about Robertson’s behaviour, spit fire for about 30 seconds in a back-and-forth, essentially calling on the league to look after quarterbacks. It’s not the first time he’s advocated for that, sharing a similar sentiment after injuring his neck following a late hit in a Week 10 win in Edmonton, and was particularly vocal last season when another Roughriders D-lineman, Garrett Marino, delivered a cheap shot to Ottawa’s Jeremiah Masoli, resulting in a season-ending knee injury. O’Shea, who is part of the CFL’s rules committee, went after the officials for their delayed reaction to what was a clear penalty. The fact the officials never saw the headbutt occur and needed the command centre to step in, not to mention Robertson wasn’t even ejected from the game, only adds to the narrative the CFL has the worst referees in all professional sports. Miller was also incensed by the play, to the point he called me over for a rare post-game interview. He said he plans to follow up with the league, advocating for a suspension, which would come a short time later, with the CFL announcing Monday afternoon Robertson has been suspended one game. 2) The Bombers once again couldn’t get their offence going out of the gate and the uninspired play continued through the first half. Collaros had zero completions on just four passing attempts in the first quarter and was also intercepted by Nick Marshall, leading to the first points by the Roughriders. By halftime, his passing numbers had jumped to 102 yards, all of which came on a TD drive just before the break, capped off with a 34-yard strike to Wolitarsky. Winnipeg’s attack had a bit more life in the second half, with Oliveira, who finished with 88 rushing yards to add to his league-leading 990, scoring twice on the ground and Sergio Castillo adding a 14-yard field goal. Nic Demski was also a bright spot, collecting a game-high 118 yards on five catches, including a 46-yarder that led to Wolitarsky’s TD. Collaros finished the game 13-for-26 for 279 yards, two TDs and an interception. It didn’t help that there were a few dropped balls, including a couple by Dalton Schoen, but Collaros needed to be more consistent for the Bombers to win. 3) The defence didn’t look bad, but they also weren’t the playmaking group that has come to define them over the last few years. And while they kept the Roughriders offence in check for large chunks of the night, forcing them to kick five field goals compared, they didn’t finish with a single turnover. They also couldn’t come up big late in the game, allowing Saskatchewan to march down the field for an easy game-tying field goal and then a TD in OT. That’s the second time an opposing offence has found pay dirt in extra time with relative ease this season, with the Ottawa Redblacks doing the same in a 31-28 win back in Week 6. The Roughriders put up 382 net offensive yards – 10 more

High blood pressure after surgery, or postoperative hypertension, is common. It has a variety of causes, including anesthesia, inflammation, and pain. High blood pressure after surgery is typically short term and resolves as the person heals. However, numerous medications can lower a person’s blood pressure, and lifestyle modifications can help blood pressure stay within a safe range. This article explains high blood pressure, examines some reasons for postoperative hypertension, and highlights how a person can manage it. High blood pressure, or hypertension, is a medical condition where the pressure in a person’s arteries is persistently high. Blood pressure readings give the following two measurements: Systolic pressure: Systolic pressure is the first, top number. It measures the pressure in the arteries when the heart beats. Diastolic pressure: Diastolic pressure is the second, bottom number. It measures the pressure in the arteries when the heart rests between beats. So if a person’s systolic pressure is 120 millimeters of mercury (mm Hg) and their diastolic pressure is 80 mm Hg, a healthcare professional may say their blood pressure is “120 over 80” or write “120/80 mm Hg.” The American Heart Association states that typical blood pressure is less than 120/80 mm Hg. It also gives the following information: Blood pressure is high when it is 120–129 mm Hg over less than 80 mm Hg. Stage 1 hypertension is when the systolic number is 130–139 mm Hg, or the diastolic number is 80–89 mm Hg. Stage 2 hypertension is when the systolic number is 140 or higher, or the diastolic number is 90 or higher. People can discuss their personal blood pressure goals with a healthcare professional. Various factors can cause postoperative hypertension, including: Preexisting hypertension People with preexisting hypertension or cardiovascular conditions are likely to experience fluctuations in blood pressure after surgery. Anesthesia Many general anesthetic drugs can affect the cardiovascular system. During anesthesia, some medications have a cardiac depressant effect, slowing heart contractions’ rate or force. They can also reduce systemic vascular resistance, which is the resistance in the circulatory system responsible for blood pressure. Additionally, when blood pressure changes, the person’s baroreflex response kicks in, and the body begins trying to regulate pressure. This process involves rapidly adjusting heart rate and the constriction or dilation of blood vessels. This means the various effects of general anesthetic medications can cause large fluctuations in blood pressure. Fluid imbalance Surgical procedures can shift the body’s fluid balance and cause high blood pressure after surgery. When a person receives IV fluids, blood transfusions, or medications during surgery, the amount of fluid in their body significantly increases. This makes it common to experience edema or weight gain after surgery. This fluid overload can also lead to high blood pressure. Inflammation Surgery triggers an inflammatory response in the body, which is the immune system’s reaction to an irritant. When inflammation occurs, the body accumulates plasma and releases leukocytes, or white blood cells, to fight pathogens and repair damage. Small blood vessels enlarge to help the plasma and leukocytes travel to the injury more easily. These processes can affect blood regulation. Pain level Surgery often causes pain and stress on the body, leading to an increase in stress hormones such as adrenaline and cortisol. These hormones can elevate blood pressure. Pain medication Some pain medications can increase blood pressure. These include nonsteroidal anti-inflammatory drugs such as aspirin, ibuprofen, and naproxen. Read about how pain medications work. High blood pressure typically has no symptoms. However, if a person’s high blood pressure turns into a hypertensive crisis, they may experience: If a person experiences these symptoms, they should seek medical attention immediately. The outlook for people with high blood pressure after surgery varies based on factors such as the individual’s overall health, the extent of the blood pressure elevation, the underlying cause, and how effectively they and their healthcare team manage it. Postoperative hypertension is common and typically resolves as the body recovers from surgical stress. Postoperative hypertension is a common physiological response to various surgery-related factors, including anesthesia, inflammation, pain, and even pain medications. Both people with preexisting hypertension and those with typical blood pressure levels can experience high blood pressure after surgery. While it usually resolves as the body heals from surgery, monitoring and managing postoperative hypertension is critical for preventing additional cardiac complications.