Individuals dealing with health problems, UTIs, and skin issues can become chronic, what are the effects and benefits of drinking cranberry juice?
Cranberry Juice
Cranberries are a healthy source of nutrients and antioxidants. Cranberry juice is a recommended source of vitamin C, with the added benefits of promoting digestive, heart, immune, and skin health. Most individuals can safely drink cranberry juice to their diet with no issues, but women who are pregnant or individuals that take blood thinners, or medications should discuss adding cranberry intake with a doctor or specialist first.
One cup of unsweetened cranberry juice provides 23.5 milligrams or 26% of the daily value for vitamin C. (USDA 2018)
To avoid excess consumption of added sugars and maximize the benefits, it is recommended to drink unsweetened cranberry juice.
Digestive Health
Cranberries contain antioxidant compounds/polyphenolsthat have been shown to help with digestive health.
A study found that drinking cranberry juice was associated with increased beneficial gut bacteria and decreased constipation.
Research funded by a cranberry juice company found participants who consumed cranberry juice twice daily had lower levels of several risk factors for heart disease, stroke, and diabetes than those who received a placebo. (USDA 2016)
A systematic review and meta-analysis found that cranberry supplementation may improve body weight and blood pressure levels.
Cranberries may also help improve high-density lipoprotein (HDL) cholesterol—considered “good” cholesterol—in younger adults.
Cranberry juice contains vitamin C, which is important for immune system function.
Research suggests that inadequate vitamin C consumption can lead to decreased immunity and an increased risk of infections. (Carr A, Maggini S, 2017)
Skin Health
Thanks to its high antioxidant content, cranberry juice may help protect your skin against damage caused by free radicals that contributes to premature aging.
The vitamin C in cranberry juice is also needed for collagen production.
Collagen is a type of protein that provides strength, elasticity, and structural support to the skin, helping to keep it firm and smooth.(Pullar JM, et al., 2017)
Infection Prevention
A study found that cranberry components known as proanthocyanidins, can promote oral health.
Cranberries activate antibacterial processes that can prevent bacteria from binding together, reducing periodontitis/gum disease and the formation of dental plaque. (Chen H, et al., 2022)
Urinary Tract Infection Prevention
Cranberries have gone through many studies for home treatment of UTIs.
It is believed the chemical compounds/proanthocyanidins can help prevent certain bacteria from sticking to the lining of the urinary tract, thus reducing the risk of UTIs. (Das S. 2020)
A study found cranberry products in the form of juice or tablets may lower the risk of UTIs in at-risk groups by approximately 30%.
At-risk groups include those with recurrent UTIs, pregnant women, older adults, and individuals with chronic indwelling catheters (devices used for short-term bladder drainage) and neurogenic bladder (conditions in which people lack bladder control due to problems in the brain, spine, or spinal cord). (Xia J Yue, et al., 2021)
Daily Amount
There is no official recommendation on the optimal amount of juice an individual should consume for health benefits. Most studies examining the benefits have used amounts ranging from 8 to 16 ounces, or around 1 to 2 cups per day. (The Cranberry Institute) However, cranberry juice with large amounts of added sugar can contribute to increased calories, leading to weight gain and other health concerns. Therefore, it is important to read the product label and look for pure, 100% cranberry juice.
If the pure juice is too tart, dilute it with some ice or water.
Avoid cranberry cocktails that are often mixed with other juices, like grape or apple juice, and contain added sugars that can decrease the benefits.
Chicas MC, Talcott S, Talcott S, Sirven M. Effect of cranberry juice supplementation on the gut microbiome and inflammatory markers: a randomized, double-blind, placebo-controlled study in overweight individuals. Curr Dev Nutr. 2022;6(Suppl 1):272. doi:10.1093/cdn/nzac053.013
Chen H, Wang W, Yu S, Wang H, Tian Z, Zhu S. Procyanidins and their therapeutic potential against oral diseases. Molecules. 2022;27(9):2932. doi:10.3390/molecules27092932
Pourmasoumi M, Hadi A, Najafgholizadeh A, Joukar F, Mansour-Ghanaei F. The effects of cranberry on cardiovascular metabolic risk factors: A systematic review and meta-analysis. Clinical Nutrition. 2020;39(3):774-788. doi:10.1016/j.clnu.2019.04.003
Pullar JM, Carr AC, Vissers MCM. The roles of vitamin C in skin health. Nutrients. 2017;9(8):866. doi:10.3390/nu9080866
Xia J Yue, Yang C, Xu D Feng, Xia H, Yang L Gang, Sun G ju. Consumption of cranberry as adjuvant therapy for urinary tract infections in susceptible populations: A systematic review and meta-analysis with trial sequential analysis. PLoS One. 2021;16(9):e0256992. doi:10.1371/journal.pone.0256992
Dr. Jimenez, D.C., presents how chronic infections are associated with Lyme disease in this 3-part series. Many environmental factors often play a role in our health and wellness. In today’s presentation, we look at genes and how to answer the right questions. Part 12 looked at what Lyme disease does to the body. Part 3 looks at treatment protocols for Lyme disease. We mention our patients to certified medical providers that provide available therapy treatments for individuals suffering from chronic infections associated with Lyme disease. We encourage each patient when it is appropriate by referring them to associated medical providers based on their diagnosis or needs. We understand and accept that education is a marvelous way when asking our providers’ crucial questions at the patient’s request and acknowledgment. Dr. Alex Jimenez, D.C., uses this information as an educational service. Disclaimer
Chronic Infections
Dr. Alex Jimenez, D.C., presents: We will have an interesting, brief discussion about evidence of an atomic force micrograph of a borrelia burgdorferi biofilm. This is a talk about stealth pathology and chronic infection in general, and we are using Lyme as a backdrop, but this is far from a comprehensive course on Lyme disease. So, let’s dive in because we are going to learn a lot about stealth pathology and a lot about Lyme disease. How do you begin thinking about chronic occult infection and stealth pathology? It starts with the basic functional medicine model.
It would help if you dealt with the phenotype. You know, your genes are not your destiny. Well, your phenotype isn’t your destiny either because it’s malleable. And how do we change your phenotype by dealing with the exposome, internal exposome, lifestyle issues, air, water, food pollution, medications, environmental toxins, xenobiotics, those kinds of things? Other exposomes include internal metabolic byproducts, lipid peroxides, oxidative stress, protein addicts, inflammation, the microbiome, et cetera. And then cognitive thoughts, beliefs, fears, phobias, isolation stressors, et cetera. And these cognitive processes have profound effects on immune responses. And then, on top of that, you have to deal with the pathogen. You must understand the biology, life cycle, and genetics of the pathogen you’re dealing with. You must also understand the pathophysiology, stealth pathology, cooperation, biofilm production, and interactions with the host immune system. And it’s important to remember that we’re talking about chronic infection here, not acute infection.
Acute Infections
Dr. Alex Jimenez, D.C., presents: If your patient has an acute infection, like pneumonia or meningitis, get them on IV antibiotics immediately, and don’t wait for your functional medicine workup. So how do you even begin to think about this? Well, you start with a comprehensive physical exam and look carefully at the question, when was the last time your patient was truly well? We like to think of it like this. If wellness is a straight line at some point, it broke right at that place, right around there. This can happen several times, so it might have broken ten years ago. And they came along with this new normal, but it broke numerous times again. And so, at each of those breaks in the overall health, what happened? What were the antecedents? What were the triggers?
Mediators For Genes
Dr. Alex Jimenez, D.C., presents: What were the mediators? And then, look at a physical and nutritional exam and, again, for antecedent triggers and mediators. And then create a timeline to look for the antecedent triggers and mediators. People come with baggage. They’ve been given this diagnosis and that diagnosis. And the other diagnosis, you know, they might have seronegative, rheumatoid arthritis, they might have fibromyalgia, chronic fatigue syndrome, maybe somebody said they had Epstein-Barr virus. Whatever it is, we need to look at those diagnoses critically and do whatever’s necessary. More tests, consultations, whatever’s required to rule it in or out. And from there, we populate a matrix. And this matrix is a living document because every time a new bit of data comes in, we need to fit that into the matrix.
The functional medicine workup has a layer on the bug’s biology and pathophysiology. And here is what we call the infectious Denee disease conundrum in these five areas where these bacteria seem to be able to figure out how to evade antibiotic and antimicrobial herbs and pharmaceuticals and our immune system. And then always remember the fundamental functional medicine adage, which is, unless there is a compelling reason to do otherwise, start in the gut. So start in the gut unless there’s a compelling reason to do otherwise, and here is why. So baseline nutritional deficiencies can be caused by many different antecedences and triggers. Let’s take just one as an example. People are in autonomic dysregulation, causing fight-or-flight responses. Fight or flight shunts blood away from your gut, which means you are not digesting or absorbing efficiently.
How Do Chronic Infections Affect The Body
Dr. Alex Jimenez, D.C., presents: That means that you’re functionally malnourished. Also, you’re shunting blood away from your gall. So the gut-associated lymphoid tissue comprises 70% of your entire immune system, intimately associated with the gut; you’re shunting blood away from that. So you’re functionally immune compromised just from autonomic balance issues. So what does cause increased baseline oxidative stress, impaired immune function, and impaired mucosal defenses that result in the proliferation of some of these endogenous viruses? In middle teens, you are colonized or dormant, infected with Epstein-Barr, cytomegalovirus, and some herpes simplex viruses may bloom. That increases your susceptibility to infection. These things increase the frequency, severity, and duration of infection. And here’s where amplification loops begin. This causes exacerbations in oxidative stress in your mucosal damage.
And then sick behaviors of anorexia and so on result in these amplification loops. And now, the problem is getting bigger and bigger, and the body’s ability to solve this problem is shrinking. And that’s where functional medicine interventions are so powerful and important. And the question always comes up, “Do I have enough time? Do I have enough data, if you will, to even begin treatment?” We want to simplify functional medicine to show you how powerful it is. Let’s say assimilation is an example. We’re just going to pick four ways to intervene in assimilation. We’re going to say there’s no problem in assimilation, so we’re not going to do anything. Or there’s a mild problem. So we’re going to put them on an elimination diet; maybe there’s a more moderate problem.
Conclusion
Dr. Alex Jimenez, D.C., presents: So we’re going to add to that elimination diet, say, colostrum. And then, for a severe problem, we’re going to layer on top of that a GI-focused medical food. So this is a more complex medical food. So we have these four interventions. Now, we’re considering intervening at all the functional medicine matrix nodes. In that case, we have the, you know, the seven physiologic nodes, what we think are often overlooked, the mental, emotional, and spiritual domains of wellness, the five modifiable lifestyle factors, and so on. So you end up with about 19 and more if you’re doing labs because you’ll intervene on all those. But four to the 19th power is the number of different combinations or ways this can happen. This becomes unique in the world intervention for your patient. So never be afraid to start and do another lap around the matrix by adding more information, and think about the next step. Now, we want to talk about the quality of evidence that we find in evidence-based medicine. A 2005 research paper published by Dr. Iondas titled “Why Most Published Research Finds Are False?” The research shows an increasing concern that most current published research findings are false, as studies show that many claims are more false than true for many designs and settings. The research is more or less an accurate measure of the prevailing bias.
Wrestling is a sport that requires speed, strength, and endurance that involves intense physical contact, pushing and pulling the muscles, tendons, ligaments, and joints to their limits. Wrestlers’ are constantly contorting their bodies. Pushing the body to its limits increases the risk of developing wrestling injuries that include:
The most common injuries usually occur from forceful contact or twisting forces. And if a wrestler has been injured, there is an increase for re-injury. Wrestling tournaments typically take place over days, often with back-to-back matches, which significantly fatigues the body and increases injury risk. The most common wrestling injuries include:
Muscle strains of the lower extremities and/or the back.
Chronic problems can result from hours in the forward stance posture and repetitive motions.
Dislocations and sprains of the elbow or shoulder from take-downs.
Cauliflower ear – is a condition that can cause ear deformity and develops from friction or blunt trauma to the ears.
Skin infections occur from constant contact, sweating, bleeding, and rolling on the mats. Infections include herpes gladitorium, impetigo, folliculitis, abscesses, and tinea/ringworm.
Concussions are usually caused by hard falls/slams or violent collisions with the other wrestler.
Injuries can cause wrestlers to alter/change their technique, exacerbating the existing damage and potentially creating new injuries.
Chiropractic Rehabilitation and Strengthening
There can be a variety of pain generators/causes when it comes to wrestling injuries. Joints and muscles can get overstretched, muscles can spasm, and nerves can become compressed and/or irritated. For example, a neck muscle spasm could be caused by nerve irritation from a shifted vertebrae. To determine the specific cause or causes of the injury/pain, a detailed chiropractic examination will be performed that includes:
Range of motion testing
Ligament tests
Muscle palpation
Gait testing
Injuries often relate to the proper weight, neuromuscular control, core strength, proper technique, hygiene, and hydration management. Successful treatment depends on identifying the root cause of the wrestling injury. Chiropractic restores proper alignment through massage, specific manual adjustments, decompression, and traction therapies. Adjustments can include the back, neck, shoulder, hips, elbows, knees, and feet. Once correct body alignment is achieved, rehabilitative exercises and stretches are implemented to correct and strengthen muscle function. We work with a network of regional medical doctors specializing in referral situations and strive to return the athlete to their sport as soon as possible.
Wrestling Match
References
Boden, Barry P, and Christopher G Jarvis. “Spinal injuries in sports.” Neurologic clinics vol. 26,1 (2008): 63-78; viii. doi:10.1016/j.ncl.2007.12.005
Medical experts advise that maintaining body hydration is one of the most important things to do in extreme heat. Individuals out in the heat lose electrolytes like sodium, potassium, and chloride and need added electrolytes to prevent cramping and excessive sweating that can strain the body. Dehydration can be dangerous, leading to heat exhaustion and possible heat stroke. If gulping water all day seems like a lot, remember that not all hydration must come from drinking water; there are hydrating foods that contain enough water that can be incorporated.
Sweating is vital for maintaining body temperature, and electrolytes are essential in maintaining the body’s homeostasis. Electrolytes help coordinate muscle contractions, heart function, and the conductivity of electric signals transmitting to and from the nervous system. The kidneys regulate fluid absorption and excretion to maintain electrolyte balance, but an imbalance can occur when electrolyte levels spike or drop. An electrolyte imbalance is caused by a change in the number of electrolytes in the body. Sodium, potassium, and calcium are the common elements most likely to be affected by an electrolyte imbalance. Other reasons why electrolyte levels can change include:
Unhealthy diet
Medications
Kidney problems
It is recommended that instead of focusing on how many glasses of water have been drunk, concentrate on two biomarkers:
When the body is thoroughly hydrated, an individual should go to the bathroom every two to three hours, and the urine should be a pale yellow. If it looks orange, it indicates that the body is trying to conserve water and needs further hydration.
Hydrating Foods
Consulting a doctor or nutritionist is recommended to help determine what foods are safe for the individual if there are underlying conditions or other health concerns. Here are a few hydrating foods that contain at least 80 percent water that can be eaten throughout the hot day to maintain body hydration.
Apples
Best known for their fiber content (up to 5 grams), they are also more than 80 percent water.
A quick crunchy snack with potassium, vitamin B6, C, and magnesium.
Watermelon
These can be up to 92 percent water.
Contain vitamin A, B6, and C, plus lycopene and antioxidants.
Watermelon can be cubed by itself or with feta cheese, olive oil, salt, pepper, and basil for a sweet-savory salad.
Peaches
These can contain up to 88 percent water, fiber, protein, and vitamin C.
Peaches can be added to salsas or incorporated into a salad.
Carrots
Carrots are around 90 percent water.
Rich in beta carotene, which the body uses to make vitamin A.
Vitamin A helps the eyes convert light into a signal sent to the brain, allowing for better sight in dim to dark light.
Vitamin K
Potassium
Fiber
Cucumbers
Cucumbers have more than 96 percent water.
They also contain potassium, phosphorus, magnesium, and some calcium.
They contain nutrients known as cucurbitacins, which can have an anti-diabetic effect.
Fisetin is an anti-inflammatory substance that helps brain health.
Potatoes
The waxy variety contains more water, as much as 80 percent.
They contain potassium, vitamin C, fiber, and minerals.
Have them baked or roasted with skins to keep as much potassium as possible.
Tomatoes
Tomatoes are almost 95 percent water.
They contain cancer-fighting carotenoid lycopene, vitamin A and C, and potassium.
Sliced onto sandwiches, sauteed into pasta, or blended into a gazpacho.
Cantaloupe
90 percent water.
Contains beta-carotene, fiber, and vitamin C.
It can be eaten by itself, chopped into salads or smoothies.
Plain yogurt
One cup of plain yogurt is around 88 percent water.
It contains protein, gut probiotics, calcium, zinc, magnesium, potassium, and phosphorus.
Top with some berries for extra hydration.
These are a few hydrating foods that can help with the intense heat. Others include zucchini, iceberg lettuce, strawberries, blueberries, celery, broccoli, and cauliflower. Healthy H2O levels benefits include:
Decreased appetite.
Improved physical performance during exercise.
Increased energy levels.
Optimal brain function.
What Are The Most Hydrating Foods?
References
Bergeron, Michael F. “Hydration and thermal strain during tennis in the heat.” British journal of sports medicine vol. 48 Suppl 1, Suppl 1 (2014): i12-7. doi:10.1136/bjsports-2013-093256
Gauer, Robert, and Bryce K Meyers. “Heat-Related Illnesses.” American family physician vol. 99,8 (2019): 482-489.
Karppanen, H et al. “Why and how to implement sodium, potassium, calcium, and magnesium changes in food items and diets?.” Journal of human hypertension vol. 19 Suppl 3 (2005): S10-9. doi:10.1038/sj.jhh.1001955
Schiefermeier-Mach, Natalia, et al. “Electrolyte Intake and Major Food Sources of Sodium, Potassium, Calcium, and Magnesium among a Population in Western Austria.” Nutrients vol. 12,7 1956. 30 Jun. 2020, doi:10.3390/nu12071956
Strimbu, Kyle, and Jorge A Tavel. “What are biomarkers?.” Current opinion in HIV and AIDS vol. 5,6 (2010): 463-6. doi:10.1097/COH.0b013e32833ed177
Ear problems like blockages or congestion can cause irritation and pain, as well as symptoms such as dizziness, ear discomfort, headaches, and sinus pain that can lead to infection. This condition can happen to anyone but is prevalent in children, individuals that live in high altitudes, and individuals who suffer from allergies. Spinal misalignments can cause interference to the nervous system that can create problems elsewhere in the body, like the ears.
If there is neck misalignment along with pinched, tangled nerve/s signal transmissions can misfire or cut off messages disrupting the process of draining the Eustachian tube. This creates a buildup of bacteria and fluid, which can cause pain and pressure. Chiropractic decompression treatment uses gentle manipulation of the cervical spine to release the pressure affecting the ear.
Ear Problems
Bacteria or viruses cause ear infections in the middle ear. Infection often results from another illness like cold, sore throat, flu, respiratory disease, or allergies that causes congestion and swelling of the nasal passages, throat, and eustachian tubes.
Eustachian Tubes
The tubes functions include:
Regulating air pressure in the middle ear
Resupply fresh air in the ear
Drain the middle ear
The eustachian tubes are two canals that connect the middle ear to the throat and nasal cavity, known as the nasopharynx. (The eustachian tubes are more narrow in children, which makes them difficult to drain and more likely to get clogged.)When the lining of these canals comes under stress, they can become inflamed/swollen, blocking or filling with fluid causing excessive pressure and pain. This fluid can become infected and cause ear infection symptoms.
If the ear problem is connected to a misalignment of the cervical spine, the following symptoms may be experienced:
Fluid/effusion stays in the middle ear for an extended time.
It can build up over and over, despite no infection.
It can also affect hearing.
Misalignment in the upper cervical spine can cause muscles to flex awkwardly/irregularly, disrupting the opening and closing of the eustachian tubes and their positioning. This often causes inflammation along the eustachian canal, upper throat, and nasal cavity. If left untreated, the inflammation can develop into an infection, causing swelling and/or fluid buildup in the inner and middle ear. Common symptoms of middle ear infections in adults include:
Pain in one or both ears
Hearing is muffled
Sore throat
Fluid drainage from the ear
Chiropractic Realignment
Treatments are helpful for individuals who want to reduce taking antibiotics, which can minimize immunity by destroying the healthy bacteria in the gut. Chiropractic is a simple and effective way to treat ear problems. Realigning the vertebrae relieves tissue inflammation/swelling around the Eustachian tube to allow drainage, relieve pressure, and restore health.
Spinal Decompression Chiropractor
References
Collins, Rachael, et al. “Paralysis from an ear infection: a severe case of otitis externa leading to acute complete cervical cord syndrome.” BMJ case reports vol. 14,12 e245594. 1 Dec. 2021, doi:10.1136/bcr-2021-245594
Harmes, Kathryn M et al. “Otitis media: diagnosis and treatment.” American family physician vol. 88,7 (2013): 435-40.
Laulajainen Hongisto, Anu et al. “Severe Acute Otitis Media and Acute Mastoiditis in Adults.” The journal of international advanced otology vol. 12,3 (2016): 224-230. doi:10.5152/iao.2016.2620
Murphy, D R. “Chiropractic rehabilitation of the cervical spine.” Journal of manipulative and physiological therapeutics vol. 23,6 (2000): 404-8. doi:10.1067/mmt.2000.108143
Polkinghorn, B S. “Treatment of cervical disc protrusions via instrumental chiropractic adjustment.” Journal of manipulative and physiological therapeutics vol. 21,2 (1998): 114-21.
Central nervous system, or CNS, infections can be life-threatening if they are not diagnosed and treated early. Because CNS infections are non-specific, determining an accurate diagnosis can be challenging. The nucleic acid in vitro amplification-based molecular methods are starting to be utilized for routine microbial diagnosis. These molecular methods have improved beyond conventional diagnostic techniques with increased sensitivity and specificity. Moreover, molecular methods utilized on cerebrospinal fluid samples are considered the new standard for diagnosis of CNS infections caused by pathogens. �
Molecular methods for the diagnosis of CNS infections offers a variety of monoplex and multiplex PCR assays to diagnose several types of health issues. Pan-omic molecular platforms can also help diagnose CNS infections. Although molecular methods are utilized for the diagnosis of CNS infections, the outcome measures for these diagnostic techniques must be carefully identified by healthcare professionals. The following article discusses conventional diagnostic techniques and molecular methods utilized for the diagnosis of central nervous system infections, their application, and future approaches. �
Molecular Methods in the Diagnosis of CNS Infections
Because of increased sensitivity and specificity, nucleic acid in vitro amplification-based molecular methods has tremendously improved the ability to diagnose CNS infections in a reasonable and effective time frame. Several PCR-derived techniques have also ultimately increased the flexibility and rigor of currently available diagnostic techniques. �
Reverse transcriptase, or RT,-PCR was developed to increase RNA targets. Its utilization plays a fundamental role in the diagnosis of RNA-virus infections as well as managing their reaction to treatment. Timely access to enterovirus RT-PCR outcome measures has demonstrated shorter hospital stays, reduced unnecessary antibiotic utilization, and decreased ancillary laboratory evaluations and tests. Broad-range rRNA PCR techniques, which utilize a single pair of primers targeting conserved regions of genes, have been utilized to diagnose bacterial pathogens and herpes viruses in the CSF. Isothermal amplification-based techniques. including loop-mediated isothermal amplification or LAMP, have been developed to offer a diagnosis within several minutes to hours. Table 2 demonstrates commercial molecular in vitro diagnostic devices, or IVD, which have been cleared by the US Food and Drug Administration, or FDA, for diagnosis of microbial pathogens in CSF. �
Monoplex Assays
A conventional molecular method involves three phases: sample extraction, target nucleic acid amplification, and amplicon detection. One of the first molecular assays successfully utilized for the diagnosis of CNS infections was utilized for the diagnosis of HSV in cerebrospinal fluid or CSF. PCR became the test of choice when research studies demonstrated that CSF PCR was similar to culture of brain tissue for diagnosis of HSV encephalitis and meningitis. Many PCR based methods for the diagnosis of herpes and enteroviruses have become available with increased sensitivity compared to viral culture. �
Real-time PCR with nucleic acid amplification and amplicon detection further improved the transition to molecular methods in clinical laboratories. Unlike conventional PCR, the real-time system is a �closed� system and it overcomes the fundamental problem of carryover contamination. At the time of manuscript preparation, three molecular assays utilized to help diagnose HSV and enteroviruses in CSF have ultimately been approved by the FDA as demonstrated in Table 2 of the previous article. � Real-time PCR-based methods are the main diagnostic technique utilized to help diagnose the Zika virus, which was first reported in Uganda in 1947, and is now a worldwide concern after the virus spread widely in Brazil and Central America. Research studies developed a one-step RT-PCR assay utilized to diagnose the Zika virus in human serum with a limited detection of 7.7pfu/reaction. Along with plasma, the Zika virus RNA can be diagnosed through urine and plasma within the first 2 weeks after symptoms have manifested. In March 2016, the FDA approved a trioplex-PCR assay under emergency use authorization for the simultaneous diagnosis of Zika, Chikungunya, and Dengue viruses in serum, urine, CSF and amniotic fluid. The RT-PCR assay utilizes dual labeled hydrolysis probes with a LOD of 1.54�10 4 GCE/ ml of Zika virus in serum. �
Introduction of real-time PCR based diagnostic assays have affected early and effective diagnosis of several bacterial infections. Isothermal amplification-based molecular assays have excellent performance characteristics and they don’t require any specialized equipment. These assays are fundamental for the utilization of on or near point-of-care testing. LAMP-based methods have been utilized to diagnose Neisseria meningitis, Streptococcus pneumoniae, Haemophilus influenzae type b, M. tuberculosis, and JEV in the CSF. The Xpert MTB/RIF assay has tremendously improved regulation of tuberculosis by offering an integrated and automated system which allows quick clinical decision making in a POC or near-care context. Several research studies have utilized the Xpert MTB/RIF to evaluate the diagnosis of M. tuberculosis in CSF from TB meningitis. In a meta-analysis of thirteen research studies, the pooled sensitivity of the Xpert assay was 80.5 percent, or 95 percent CI 59.0 percent to 92.2 percent, against culture and 62.8 percent, or 95 percent CI 47.7 percent to 75.8 percent, against composite standard. Utilizing a large volume of sample, of at least 8�10 ml, is necessary for testing CSF and centrifugation can cause considerable improvements in yield. Despite the lack of standardization for sample processing, WHO has allowed testing CSF with the automated Xpert MTB/RIF assay as the first-line test over conventional microscopy. �
Multiplex Assays
Simplicity makes multiplex molecular assays fundamental for the diagnosis of a panel of microbial targets. Several multiplex PCR assays have been developed to diagnose bacterial pathogens in CSF targeting the most common causes of meningitis: S. pneumoniae, N. meningitis, H. influenzae, L. monocytogenes, S. agalactiae, S. aureus, E. coli, and M. pneumoniae. A multiplex PCR followed by Luminex suspension array can simultaneously diagnose eight bacterial and viral pathogens in CSF, including N. meningitis, S. pueumoniae, E. coli, S. aureus, L. monocytogenes, S. agalactiae, HSV-1/2, and VZV, among others. �
Considering the variety of pathogens involved in CNS infection, application of comprehensive molecular panels with multiple bacterial and viral targets have improved the efficiency of diagnosis. The BioFire FilmArray Meningitis/Encephalitis panel is currently the only FDA cleared multiplex assay utilized for the diagnosis of six bacterial, such as Escherichia coli K1, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitides, Streptococcus agalactiae and Streptococcus pneumoniae, seven viral, such as cytomegalovirus, enterovirus, HSV-1, HSV-2, human herpesvirus 6 or HHV-6, human parechovirus and VZV, as well as a single fungal, such as Cryptococcus neoformans/gattii, target in CSF as demonstrated in Table 2. The integrated FilmArray system takes about an hour, with only 2 minutes of hands-on time. During the preparation of the manuscript, two research studies demonstrated the performance of this assay. Utilizing 48 samples from gram stain negative CSF samples from suspected cases of meningitis, research studies demonstrated that this system diagnosed more viral pathogens, such as EBV. Four cases of WNV and a single case of Histoplasma were not diagnosed by this assay. Among HIV infected patients in Uganda, the test performance demonstrated increased sensitivity and specificity for the diagnosis of Cryptococcus. Although the FilmArray Meningitis/Encephalitis panel offers a quick diagnosis of CNS infections, further research studies are needed to determine its performance for a variety of targets and other high-risk populations. �
Co-infections are frequently found among immunocompromised patients and can ultimately be challenging to diagnose for clinicians. The multiplex design allows simultaneous diagnosis of multiple targets on the same sample. One research study utilized a panel of monoplex and multiplex molecular assays to conduct a prospective cohort research study in Uganda to comprehensively evaluate the etiology of meningitis among HIV-infected adults. Among the 314 HIV-infected patients with meningitis, EBV co-infection was diagnosed with Cryptococcus, M. tuberculosis, or other viral pathogens. EBV in CSF in these settings is not completely understood although a single research study associated increased EBV viral load as a marker of poor outcome measures in patients with bacterial meningitis and EBV co-infection/ reactivation, among others. �
Pan-Omic Molecular Assays
Technological improvements in metagenomic deep sequencing have increased its utilization for clinical diagnosis of CNS infections. Several research studies have demonstrated its ability to solve diagnostic technique problems which challenge the limits of traditional laboratory testing. Due to sterile status and protection by BBB, CSF and brain biopsies are fundamental to further explore the utilization of this technology for pathogen diagnosis. Metagenomics was successfully utilized to establish a diagnosis of neuroleptospirosis in a 14-year-old boy with severe combined immunodeficiency who also suffered from recurrent bouts of fever, headache, and coma. Similarly, high-throughput RNA sequencing performed on brain biopsy from an 18-month-old boy with encephalopathy diagnosed a new Astrovirus as the cause. Despite the utilization of metagenomics for the diagnosis of infectious disease, there are many technological and practical concerns which need to be addressed before this form of diagnostic testing can become mainstream and part of the clinical standard of care. �
Other promising advances have occurred in transcriptomics, proteomics and metabolomics. Host and microbial microRNA or miRNA, profiles have been utilized for a variety of inflammatory and infectious diseases. Two miRNAs, miR-155 and miRNA-29b, were reported as potential biomarkers for JEV infection and treatment targets for anti-JEV therapy. Host neural epidermal growth factor, including 2 and apolipoprotein B in CSF, was able to diagnose tuberculous meningitis with 83.3 percent to 89.3 percent sensitivity and 75 percent to 92 percent specificity. CSF metabolite profiling has been reported to be useful in the classification, diagnosis, epidemiology, and treatment assessment of CNS infections in HIV patients. CSF metabolic profile analysis demonstrated bioenergetic adaptation in regulating shifts of HIV-infected patients. �
Outcome Measures Associated with Diseases
Diagnosis of an etiologic agent in patients with CNS infections needs consideration of the most common causative organisms, the available diagnostic techniques and molecular methods for these agents, and the highest-yield clinical specimens for evaluation and testing. Knowledge of the epidemiology and clinical presentation of specific agents is fundamental in selecting which diagnostic methods are appropriate for patients. Animal or vector exposures, geographic location, recent travel history, season of the year, exposure of ill contacts, and occupational exposures should be considered. �
When selecting appropriate pathogen-specific molecular diagnostic methods, the following factors should be considered. CSF is the optimal specimen for PCR testing for patients with meningitis or meningoencephalitis. While indirect evidence can be determined by testing other specimen types, attempts should be made to obtain CSF samples early before treatment can compromise yield. Time of testing from the manifestation of symptoms is fundamental to understand and rule out false-negative results and recommend retesting within a certain time frame. By way of instance, HSV PCR can commonly render false-negative results if CSF sample is obtained very early or late in the process of HSE infection. Host health is also known to affect test performance characteristics. Immunocompromised patients are at risk for infection by a variety of opportunistic pathogens, by way of instance HHV-6, JC virus, Toxoplasma encephalitis in bone marrow transplant recipients and patients with HIV. Often, infection can be more severe, such as WNV, and challenging to diagnose in this population. Table 3 below demonstrates practical recommendations on application and pitfalls of molecular test for the diagnosis of CNS infections. �
Furthermore, a positive nucleic acid amplification testing results are considered to be complicated by the fact that some viruses survive latently in macrophages or neurologic tissues even if they’re incidentally diagnosed by sensitive molecular techniques without an actual pathogenic role which can potentially lead to overtreatment. Utilization of adjunctive biomarkers which help determine active replication is being explored to overcome this drawback in research studies. �
Historically, the diagnosis of microbiologic agents in patients with CNS infections has been hindered by the low yield of CSF culture for viral and fastidious bacterial organisms, delays in CNS production of organism-specific antibodies, and challenges in determining optimum samples for testing. The nucleic acid in vitro amplification-based molecular diagnostic methods and techniques have a wider and better application in clinical microbiology practice. The monoplex assay will likely be the main platform utilized for urgent, random-access, low throughput assays. Multiplex assays have the additional benefit of diagnosing multiple targets and mixed infections. As the volume of CSF sample retrieved is often small, multiplex assays enable comprehensive diagnostic analysis with a low amount of sample, obviating the need for repeated lumbar punctures. The clinical relevance and cost-effectiveness of simultaneous multi-pathogen diagnosis strategies need further research studies. Application of pan-omic techniques in challenging to diagnose CNS infections is the new exciting frontier, the technology is promising but routine implementation is expected to be slow due to various challenges, such as lack of applicable regulatory guidelines and adaptation in the clinical setting, although the outcome measures are promising. �
As previously mentioned, central nervous system, or CNS, infections can be life-threatening health issues if they are not accurately diagnosed and properly treated. However, determining a diagnosis of CNS infections can be challenging for many clinicians. Fortunately, a variety of diagnostic techniques and molecular methods can ultimately help determine the source of CNS infections and other health issues. These diagnostic techniques and molecular methods have tremendously improved over the years, as previously mentioned, and more of these evaluations are being utilized in clinical settings to accurately diagnose CNS infections for proper treatment. – Dr. Alex Jimenez D.C., C.C.S.T. Insight
In part 2 of our “Diagnosis of Central Nervous System Infections” article, we discussed the molecular methods and the pan-omic molecular assays which are utilized in the diagnosis of CNS infections as well as how specific testing outcome measures have ultimately been associated with clinical diseases and health issues. The scope of our information is limited to chiropractic, musculoskeletal and nervous health issues as well as functional medicine articles, topics, and discussions. To further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900 . �
Curated by Dr. Alex Jimenez �
Additional Topic Discussion: Chronic Pain
Sudden pain is a natural response of the nervous system which helps to demonstrate possible injury. By way of instance, pain signals travel from an injured region through the nerves and spinal cord to the brain. Pain is generally less severe as the injury heals, however, chronic pain is different than the average type of pain. With chronic pain, the human body will continue sending pain signals to the brain, regardless if the injury has healed. Chronic pain can last for several weeks to even several years. Chronic pain can tremendously affect a patient’s mobility and it can reduce flexibility, strength, and endurance.
Neural Zoomer Plus for Neurological Disease
Dr. Alex Jimenez utilizes a series of tests to help evaluate neurological diseases. The Neural ZoomerTM Plus is an array of neurological autoantibodies which offers specific antibody-to-antigen recognition. The Vibrant Neural ZoomerTM Plus is designed to assess an individual�s reactivity to 48 neurological antigens with connections to a variety of neurologically related diseases. The Vibrant Neural ZoomerTM Plus aims to reduce neurological conditions by empowering patients and physicians with a vital resource for early risk detection and an enhanced focus on personalized primary prevention. �
Formulas for Methylation Support
XYMOGEN�s Exclusive Professional Formulas are available through select licensed health care professionals. The internet sale and discounting of XYMOGEN formulas are strictly prohibited.
Proudly,�Dr. Alexander Jimenez makes XYMOGEN formulas available only to patients under our care.
Please call our office in order for us to assign a doctor consultation for immediate access.
If you are a patient of Injury Medical & Chiropractic�Clinic, you may inquire about XYMOGEN by calling 915-850-0900.
�
For your convenience and review of the XYMOGEN products please review the following link.*XYMOGEN-Catalog-Download �
* All of the above XYMOGEN policies remain strictly in force.
The central nervous system, or CNS, plays a fundamental role in the pathogenesis of infection. The CNS is regulated by the blood-brain barrier or BBB, however, it can still be exposed to a microbial invasion from a contiguous focus, hematogenous dissemination, or intraneural passage of organisms. A variety of environmental or commensal bacteria, viruses, fungi, protozoa, or parasites can enter the CNS and cause a variety of infections and health issues. Central nervous system infections can ultimately cause headache, stiff neck, vomiting, fever, photophobia, and focal neurological symptoms. �
What are Central Nervous System Infections?
CNS infections are characterized according to their affected region. Infection of the brain, spinal cord, and meninges results in meningitis, encephalitis, brain abscess, and myelitis. Infections can affect single or multiple regions of the brain, such as meningoencephalitis and encephalomyelitis. Moreover, CNS infections are characterized as acute, sub-acute, chronic, or recurrent based on their duration. Meningitis can cause headache, neck stiffness, fever, and photophobia over a period of hours to days. Encephalitis can cause brain parenchymal inflammation which can ultimately cause lethargy to coma. Last but not least, Myelitis can cause inflammation of the spinal cord including headache, fever, and paraparesis or paralysis. �
One of the most fatal CNS infections, acute bacterial meningitis, with three to five cases for every 100,000 people in the United States, has a mortality rate of 6 percent to 26 percent. Approximately 4,000 cases of acute bacterial meningitis occur in the U.S. every year with about 500 deaths. The frequent cause of acute bacterial meningitis includes Streptococcus pneumoniae, group B Streptococcus, Neisseria meningitides, Haemophilus influenzae, and Listeria monocytogenes. �
CNS infections caused by viruses are more common and are mostly mild and self-limited. However, these can manifest as meningitis and/or encephalitis. CNS infections caused by viruses can vary due to region and season. Non-polio enteroviruses are responsible for the majority of meningitis and/or encephalitis cases from late spring to fall. CNS infections due to herpes simplex viruses, or HSV, are associated with sporadic encephalitis and meningitis with severe sequelae if left untreated. �
Diagnosis of CNS Infections
Diagnosis of microbial pathogens is fundamental for treatment. Methods and techniques utilized in clinical microbiology laboratories include direct microscopic examination, and culture techniques as well as antigen and antibody detection assays. However, each method and technique has several essential limitations. By way of instance, direct microscopic examination of CSF restricted sensitivity and specificity. The sensitivity of culture for enteroviruses is between 65 percent to 75 percent with average retrieval time of 3.7 to 8.2 days. Moreover, several serotypes of enteroviruses, especially Coxsackievirus A strains, are well-known to be non-cultivable and frequently grow poorly. Because enteroviruses are missing a common antigen found throughout a variety of serotypes, universal antigen and/or antibody diagnosis is impossible. Diagnosis of CNS HSV infections through methods and techniques utilized to determine culture sensitivity from CSF is tremendously poor. The presence of HSV IgG antibodies in CSF can ultimately be utilized to determine a diagnosis, however, the production is delayed until day 10 or day 12 after infection and it is not considered ideal for early diagnosis.
Diagnostic techniques, especially PCR based amplification, have developed a variety of mainstay tools to help determine the diagnosis of microbial pathogens in CSF. Molecular methods have demonstrated greater diagnosis rates than other diagnostic techniques. One research study demonstrated that 16S rRNA PCR-based assays were able to diagnose the causative organism in 65 percent of banked CSF samples compared to 35 percent when utilizing culture and microscopy. In another research study, diagnosis based on diagnostic techniques like molecular methods were utilized to optimize antibiotic treatment of patients with infectious meningitis when conventional methods and techniques demonstrated a negative outcome measure. Molecular methods and diagnostic techniques utilized on CSF samples are a fundamental standard when compared to the culture standard in the diagnosis of CNS infections caused by viruses which are challenging to diagnose. �
The diagnosis of CNS infections has tremendously changed over the last several years. PCR-based molecular methods have become a fundamental element in the clinical microbiology laboratory, providing tools for an accurate diagnosis. As demonstrated in Table 2, a variety of commercial molecular assays have been cleared by the Food and Drug Administration, or FDA, for the diagnosis of microbial pathogens. The approved assays for pathogen detection in the CNS are shown below. �
However, there are still several challenges in molecular diagnostic techniques and methods. Utilizing a combination of conventional diagnostic techniques and molecular methods, research studies demonstrated that in approximately 62 percent of patients with encephalitis, an etiologic organism could not be identified. Researchers have started to focus on developing advanced techniques and methods. In the following series of articles, we will demonstrate an update on the current conventional and molecular platforms utilized for the diagnosis of CNS infections. We will also demonstrate a preview on the potential clinical application of future technologies, including pan-omic assays. The emphasis of the following series of articles is to demonstrate optimal test selection in the clinical scenario for the diagnosis of CNS infection. �
Conventional Microbiology Methods and Techniques
Microscopic Examination
A positive CSF Gram stain confirms the diagnosis of bacterial meningitis. The sensitivity of the Gram stain for the diagnosis of bacterial meningitis is approximately 60 percent to 80 percent in patients not on antimicrobial treatment and approximately 40 percent to 60 percent in patients on antibacterial treatment. In one research study, Gram stain diagnosed as much as 90 percent Streptococcus pneumoniae and 50 percent Listeria monocytogenes in CSF collected from patients with bacterial meningitis confirmed by PCR 26 techniques and methods. Two organisms which are frequently diagnosed by microscopy include Mycobacterium tuberculosis by acid-fast bacillus, or AFB, staining and Cryptococcus neoformans by India ink or Gram stain. However,� the sensitivities of these techniques and methods are poor and culture is generally utilized instead. �
Culture
Culture of brain tissue can demonstrate a positive diagnosis of CNS infections, however, getting biopsies are tremendously invasive and frequently avoided unless a clinician determines that they are absolutely necessary. CSF sampling is most commonly performed to diagnose CNS infection. CSF viral, bacterial, including mycobacterial, and fungal cultures are fundamental in the diagnosis of infectious meningitis. However, CSF cultures in these cases are extremely low. Another disadvantage of CSF bacterial culture is that it generally requires up to 72 hours to determine a final diagnosis. A recent research study demonstrated that CSF mycobacterial culture had a sensitivity of 22 percent and a specificity of 100 percent in the diagnosis of tuberculosis meningitis. For viruses, utilizing monoclonal antibodies through culture increased the speed and specificity. However, due to time and sensitivity, CSF viral culture is frequently unable to determine a diagnosis. �
Rapid Antigen Detection
Cryptococcal antigen is the most commonly utilized antigen assay for CNS infections. The test utilizes Cryptococcus capsular polysaccharide antigens in CSF through enzyme immunoassay to determine a diagnosis. In a single research study which evaluated patients less than 35 years of age with CNS cryptococcosis, overall sensitivity and specificity of 93 percent to 100 percent and 93 percent to 98 percent were shown. Cryptococcus is a neurotropic fungus. Polysaccharide serum antigen titers with host immune status are frequently utilized to determine the need for a lumbar puncture to evaluate the patient for CNS health issues. The baseline peak titer of polysaccharide antigen in serum or CSF has demonstrated fundamental prognostic significance with an increased titer, or peak titer less than 1:1024, associated with antifungal therapy failure. �
The diagnosis of galactomannan, or GM, antigen and 1,3 ?-D-glucan, or BDG, in CSF, can help in the diagnosis of CNS aspergillosis or other invasive fungal infection such as fusariosis. Increased BDG in serum and CSF is associated with fungal infections. Measuring the levels of BDG is a beneficial biomarker in the evaluation of fungal CNS infection. It was recently demonstrated that patients receiving effective antifungal therapy demonstrated a decrease in CSF BDG concentrations with less than 31pg/ml and for this reason, BDG titers in CSF are a beneficial biomarker when monitoring response to treatment. �
For acute bacterial meningitis, a rapid antigen assay can help diagnose for a pneumococcal capsular antigen. Several research studies have demonstrated the utilization of M. tuberculosis-specific antigens in CSF for the diagnosis of tuberculosis meningitis. M. tuberculosis Early Secreted Antigenic Target 6, or ESAT-6, has been utilized for tuberculosis meningitis. �
Serology
Serological diagnosis of CNS infections is determined by identifying IgM antibodies or by demonstrating an increase in neutralizing antibody titers between acute- and convalescent-phase CSF. Due to a delay in antibody response when symptoms have manifested, a negative antibody test cannot be utilized to rule out infections and retesting may be required. Moreover, in specific populations, such as immunocompromised patients, the tests may not offer optimum sensitivity. In most instances, nucleic acid amplification tests have surpassed antibody-based detection as the test of choice. For several CNS infections, these assays play a fundamental role. CSF IgM is the most commonly utilized test for West Nile virus, or WNV, infections. Antibodies may manifest in as soon as 3 days and may continue for up to 3 months. However, its accuracy is challenged by high cross-reactivity with other flaviviruses and associated vaccines. Antibodies in recombinant WNV E proteins can determine where cross-reacting viruses co-circulate or determine which patients have been immunized. �
Fundamental serological assays for CNS infections are utilized for the diagnosis of neurosyphilis. Neurosyphilis is determined by a positive CSF venereal disease research laboratory, or VDRL, test. Diagnosis of varicella-zoster virus, or VZV, IgG in CSF is the most common technique and/or method for the diagnosis of VZV associated with CNS infection. �
Central nervous system, or CNS, infections can ultimately be life-threatening health issues if they are not diagnosed and treated early. Determining an accurate diagnosis of CNS infections can be challenging. Fortunately, a variety of diagnostic techniques and molecular methods can help determine the source of CNS infections. These diagnostic techniques and molecular methods have tremendously improved over the years and more and more of these evaluations are being utilized in clinical settings to accurately diagnose CNS infections for early treatment. – Dr. Alex Jimenez D.C., C.C.S.T. Insight
In part 2 of our “Diagnosis of Central Nervous System Infections” article, we will ultimately discuss the molecular methods and the pan-omic molecular assays which are utilized in the diagnosis of CNS infections as well as discuss how specific testing outcome measures are associated with clinical diseases and health issues. The scope of our information is limited to chiropractic, musculoskeletal and nervous health issues as well as functional medicine articles, topics, and discussions. To further discuss the subject matter above, please feel free to ask Dr. Alex Jimenez or contact us at 915-850-0900 . �
Curated by Dr. Alex Jimenez �
Additional Topic Discussion: Chronic Pain
Sudden pain is a natural response of the nervous system which helps to demonstrate possible injury. By way of instance, pain signals travel from an injured region through the nerves and spinal cord to the brain. Pain is generally less severe as the injury heals, however, chronic pain is different than the average type of pain. With chronic pain, the human body will continue sending pain signals to the brain, regardless if the injury has healed. Chronic pain can last for several weeks to even several years. Chronic pain can tremendously affect a patient’s mobility and it can reduce flexibility, strength, and endurance.
Neural Zoomer Plus for Neurological Disease
� �
Dr. Alex Jimenez utilizes a series of tests to help evaluate neurological diseases. The Neural ZoomerTM Plus is an array of neurological autoantibodies which offers specific antibody-to-antigen recognition. The Vibrant Neural ZoomerTM Plus is designed to assess an individual�s reactivity to 48 neurological antigens with connections to a variety of neurologically related diseases. The Vibrant Neural ZoomerTM Plus aims to reduce neurological conditions by empowering patients and physicians with a vital resource for early risk detection and an enhanced focus on personalized primary prevention. �
Formulas for Methylation Support
XYMOGEN�s Exclusive Professional Formulas are available through select licensed health care professionals. The internet sale and discounting of XYMOGEN formulas are strictly prohibited.
Proudly,�Dr. Alexander Jimenez makes XYMOGEN formulas available only to patients under our care.
Please call our office in order for us to assign a doctor consultation for immediate access.
If you are a patient of Injury Medical & Chiropractic�Clinic, you may inquire about XYMOGEN by calling 915-850-0900.
�
For your convenience and review of the XYMOGEN products please review the following link.*XYMOGEN-Catalog-Download �
* All of the above XYMOGEN policies remain strictly in force.
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